Descriptor: "Autoantibodies/blood" - Searchworks@Jio Institute Digital Library Search Results

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105 results on '"Autoantibodies/blood"'

1. Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy

Author: Bastiaansen, Anna E M, de Bruijn, Marienke A A M, Schuller, Sabine L, Martinez-Hernandez, Eugenia, Brenner, Juliëtte, Paunovic, Manuela, Crijnen, Yvette S, Mulder, Maxim J H L, Schreurs, Marco W J, de Graaff, Esther, Smitt, Peter A E, Neuteboom, Rinze F, de Vries, Juna M, Titulaer, Maarten J, Sub Cell Biology, Celbiologie, Neurology, Immunology, Sub Cell Biology, and Celbiologie
Subjects: Adult, Male, Adolescent, Clinical Neurology, Anti-N-Methyl-D-Aspartate Receptor Encephalitis/blood, Netherlands/epidemiology, Article, Cohort Studies, Young Adult, Neoplasms, Diagnosis, 80 and over, Humans, Age of Onset, Preschool, Child, Netherlands, Aged, Autoantibodies, Anti-N-Methyl-D-Aspartate Receptor Encephalitis, Aged, 80 and over, Infant, Frequency, Middle Aged, Neurology, Child, Preschool, Aspartate receptor encephalitis, Female, Neurology (clinical), Autoantibodies/blood, Neoplasms/epidemiology
Abstract: Background and ObjectivesTo describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF.MethodsNationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019.ResultsOne hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1–86 years). The mean annual incidence was 1.00/million (95% CI 0.62–1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, p = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, p = 0.020), and more often undetectable serum antibodies compared with younger patients (p = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both p < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, p < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (p = 0.003), but appeared to have an equally severe disease course.DiscussionAnti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt.
Published: 2022

2. Pitfalls in the detection of myositis specific antibodies by lineblot in clinically suspected idiopathic inflammatory myopathy

Author: Yves, Piette, Maxime, De Sloovere, Stien, Vandendriessche, Joke, Dehoorne, Jan L, De Bleecker, Liesbet, Van Praet, An-Sofie, Vander Mijnsbrugge, Sofie, De Schepper, Peggy, Jacques, Filip, De Keyser, Vanessa, Smith, Carolien, Bonroy, Faculty of Medicine and Pharmacy, Clinical sciences, Medical Oncology, and Electronics and Informatics
Subjects: Myositis, Rheumatology, Immunology, Humans, Immunology and Allergy, Myositis/diagnosis, Autoantibodies/blood, Fluorescent Antibody Technique, Indirect, syndrome, Autoantibodies, Autoimmune Diseases
Abstract: OBJECTIVES: Today, the contribution of myositis-specific autoantibodies (MSA) in the diagnostic workup of idiopathic inflammatory myopathies (IIM) is on the rise. The aim of this study was to document MSA frequency as detected by lineblot in a set of consecutive MSA requests and to correlate the results with clinical diagnosis, IIM subtype and indirect immunofluorescence (IIF) findings. Additionally, a comparison between two lineblots was performed. METHODS: A total of 118 consecutive samples of patients with suspicion of IIM were analysed on IIF and two lineblots. A total of 107 patients with autoimmune rheumatic diseases served as controls. RESULTS: MSA were detected in 55% of IIM patients (n=31) and 7.9% (n=12) of patients without clinical diagnosis of IIM or myositis overlap syndrome. All the IIM patients had a MSA-compatible clinical subtype. There was no to fair agreement between both lineblots for the individual antibodies, with most discrepancies observed for anti-TIF1γ (κ=-0.021), anti-SRP (κ=-0.006) and anti-SAE (κ=0.395). Differences between both assays were mostly observed in the non-IIM patients, also showing signi cantly lower blot signal intensities compared to IIM patients (p=0.0013). MSA in the non-IIM patients frequently showed an incompatible IIF pattern. CONCLUSIONS: Lineblot seems to be an interesting tool for MSA detection in a clinical context, allowing the identification of clinical subtypes. However, considerable caution must be exercised in interpreting the results in case of low positive MSA signal intensity, discordant lineblot results and/or an incompatible IIF pattern.
Published: 2020

3. A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing

Author: Ben Mulhearn, Danyang Li, Fionnuala McMorrow, Hui Lu, Neil J. McHugh, and Sarah L. Tansley
Subjects: Immunoprecipitation/methods, autoantibodies, Immunology, Immunoblotting, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, Dermatomyositis, myositis - diagnosis, SDG 3 - Good Health and Well-being, cancer, Immunology and Allergy, Humans, Immunoprecipitation, Serologic Tests, TIF1γ, False Negative Reactions, Autoantibodies, Immunoblotting/methods, ELISA - enzyme-linked immunosorbent assay, Serologic Tests/methods, Enzyme-Linked Immunosorbent Assay/methods, Diagnostic Tests, Routine, dermatomysitis, RC581-607, Dermatomyositis/blood, Data Accuracy, Case-Control Studies, Diagnostic Tests, Routine/methods, Transcription Factors/immunology, Immunologic diseases. Allergy, Autoantibodies/blood, myositis, Transcription Factors
Abstract: ObjectivesAnti-TIF1γ is an important autoantibody in the diagnosis of cancer-associated dermatomyositis and the most common autoantibody in juvenile onset dermatomyositis. Its reliable detection is important to instigate further investigations into underlying malignancy in adults. We previously showed that commercial assays using line and dot blots do not reliably detect anti-TIF1γ. We aimed to test a new commercial ELISA and compare with previously obtained protein immunoprecipitation.MethodsRadio-labelled immunoprecipitation had previously been used to determine the autoantibody status of patients with immune-mediated inflammatory myopathies and several healthy controls. ELISA was undertaken on healthy control and anti-TIF1γ sera and compared to previous immunoprecipitation data.ResultsA total of 110 serum samples were analysed: 42 myositis patients with anti- TIF1γ and 68 autoantibody negative healthy control sera. Anti-TIF1γ was detected by ELISA in 41 out of 42 of the anti-TIF1γ-positive samples by immunoprecipitation, and in none of the healthy controls, giving a sensitivity of 97.6% and specificity of 100%. The false negative rate was 2%.ConclusionELISA is an affordable and time-efficient method which is accurate in detecting anti-TIF1γ.
Published: 2021

4. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Author: Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherios, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Liis, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicolas, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesus, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G., Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B., Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Louis, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R., Franco, José Luis, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M., Zhang, Yu, Snow, Andrew L., Holland, Steven M., Biggs, Catherine M., Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M., Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L., Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A., El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N., Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A., Dominguez-Garrido, Elena, Vidigal, Mateus, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G., Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Lluis, Klocperk, Adam, Kann, Nelli Y., Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C., Arrestier, Romain, Boudhabhay, Idris, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H., Kennelly, Sean P., Bourke, Nollaig M., Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Mehlal Sedkaoui, Souad, AlKhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C., Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bondarenko, Anastasiia, Spaan, András N., Gilardin, Laurent, Fellay, Jacques, Lyonnet, Stanislas, Bilguvar, Kaya, Lifton, Richard P., Mane, Shrikant, Anderson, Mark S., Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Andreakos, Evangelos, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H., Rowen, Lee, Mond, James, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K., Piemonti, Lorenzo, Rodríguez-Gallego, Carlos, Notarangelo, Luigi D., Su, Helen C., Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M., Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, Bigio, Benedetta, de la Chapelle, Aliénor, Chen, Jie, Chrabieh, Maya, Liu, Dana, Nemirowskaya, Yelena, Cruz, Inés Marín, Materna, Marie, Pelet, Sophie, Seeleuthner, Yoann, Thibault, Chloé, Liu, Zhiyong, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Darazam, Ilad Alavi, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, Alkhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Feldman, Hagit Baris, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Bustamante, Jacinta, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Flores, Carlos, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Gut, Marta, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Lima, Edson Jose Adrian Bolanos, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Lye, David C, Magnone, Cinthia, Mansouri, Davood, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morange, Pierre-Emmanuel, Mordacq, Clémence, Morelle, Guillaume, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Planas-Serra, Laura, Ploin, Dominique, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Gallego, Carlos, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Sediva, Anna, Seijo, Luis, Seminario, Analia Gisela, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Shahrooei, Mohammad, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Soler, Catherine, Soler-Palacín, Pere, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, THORN, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Troya, Jesús, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Danielson, Jeffrey J., Dobbs, Kerry, Kashyap, Anuj, Ding, Li, Dalgard, Clifton L., Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Bettini, Laura Rachele, D’Angio’, Mariella, Beretta, Ilaria, Montagna, Daniela, Licari, Amelia, Marseglia, Gian Luigi, Batten, Isabella, Reddy, Conor, McElheron, Matt, Noonan, Claire, Connolly, Emma, Fallon, Aoife, Storgaard, Merete, Jørgensen, Sofie, Erikstrup, Christian, Pedersen, Ole Birger, Sørensen, Erik, Mikkelsen, Susan, Dinh, Khoa Manh, Larsen, Margit Anita Hørup, Paulsen, Isabella Worlewenut, Von Stemann, Jakob Hjorth, Hansen, Morten Bagge, Townsend, Liam, Cheallaigh, Cliona Ni, Bergin, Colm, Martin-Loeches, Ignacio, Dunne, Jean, Conlon, Niall, Bourke, Nollaig, O'Farrelly, Cliona, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouadma, Lila, Bouscambert-Duchamp, Maude, Paz, Pauline Caraux, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, d’Ortenzio, Eric, De Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Alcover, Andres, Aschard, Hugues, Bousso, Philippe, Brodin, Petter, Bruhns, Pierre, Cerf-Bensussan, Nadine, Cumano, Ana, D’Enfert, Christophe, Deriano, Ludovic, Dillies, Marie-Agnès, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gomperts-Boneca, Ivo, Hasan, Milena, Hedestam, Gunilla Karlsson, Hercberg, Serge, Ingersoll, Molly A, Lantz, Olivier, Kenny, Rose Anne, Ménager, Mickaël, Michel, Frédérique, Patin, Etienne, Pellegrini, Sandra, Rausell, Antonio, Rieux-Laucat, Frédéric, Rogge, Lars, Fontes, Magnus, Sakuntabhai, Anavaj, Schwartz, Olivier, Schwikowski, Benno, Shorte, Spencer, Tangy, Frédéric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie-Noëlle, Zimmer, Christophe, Albert, Matthew L., Alavoine, Loubna, Behillil, Sylvie, Burdet, Charles, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm Jan, Bomers, Marije, Bonta, Peter, Bos, Lieuwe, Botta, Michela, de Brabander, Justin, de Bree, Godelieve, de Bruin, Sanne, Buis, David T.P., Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dijkstra, Mirjam, Dongelmans, Dave A., Dujardin, Romein W.G., Elbers, Paul, Fleuren, Lucas, Geijtenbeek, Suzanne Geerlings Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., de Jong, Menno D., Lim, Endry H.T., van Mourik, Niels, Nellen, Jeaninne, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Pina-Fuentes, Dan A.I., van der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, de Rotte, Maurits C.F.J., Schinkel, Michiel, Schultz, Marcus J., Schrauwen, Femke A.P., Schuurmans, Alex, Schuurmans, Jaap, Sigaloff, Kim, Slim, Marleen A., Smeele, Patrick, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos, Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Al-Muhsen, Saleh, Al-Mulla, Fahd, Arias, Andrés A., Bogunovic, Dusan, Bolze, Alexandre, Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Froidure, Antoine, Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein S., Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Ku, Cheng-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Milner, Joshua D., Mironska, Kristina, Ng, Lisa F.P., Novelli, Antonio, Novelli, Giuseppe, de Diego, Rebeca Perez, Renia, Laurent, Resnick, Igor, Sancho-Shimizu, Vanessa, Seppänen, Mikko R.J., Shahrooei, Mohammed, Slaby, Ondrej, Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., von Bernuth, Horst, Zawadzki, Pawel, Nadif, Rachel, Goldberg, Marcel, Ozguler, Anna, Henny, Joseph, Lemonnier, Sylvie, Coeuret-Pellicer, Mireille, Le Got, Stéphane, Tzourio, Christophe, Dufouil, Carole, Soumaré, Aïcha, Lachaize, Morgane, Fievet, Nathalie, Flaig, Amandine, Martin, Fernando, Bonneaudeau, Brigitte, Cannet, Dorothée, Gallian, Pierre, Jeanne, Michel, Perroquin, Magali, Hamzeh-Cognasse, Hind, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro [Lille], Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grand Hôpital de l'Est Francilien (GHEF), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Ballanger [Aulnay-sous-Bois], Hôpital Edouard Herriot [CHU - HCL], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Verdier [AP-HP], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, Howard Hughes Medical Institute, Rockefeller University, European Commission, Jeffrey Modell Foundation, Université de Bordeaux, Meath Foundation, National Human Genome Research Institute, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Fondation du Souffle, Instituto de Salud Carlos III, Institut National de la Santé et de la Recherche Médicale, St. Giles Foundation, Ministère des Solidarités et de la Santé, Sorbonne Université, Mutuelle Générale de l'Education Nationale, Conseil Régional Aquitaine, Conseil régional de Bourgogne-Franche-Comté, Meyer Foundation, Fondation de France, National Cancer Institute, European Regional Development Fund, Fundación DISA, Ministero della Salute, ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), European Project: IdEx Bordeaux (ANR-10-IDEX- 003-02), Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Manry, Jérémy, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Eto, Shohei, Garcia-Prat, Marina, Bizien, Lucy, Parra-Martínez, Alba, Yang, Rui, Haljasmägi, Lii, Migaud, Mélanie, Särekannu, Karita, Maslovskaja, Julia, de Prost, Nicola, Tandjaoui-Lambiotte, Yacine, Luyt, Charles-Edouard, Amador-Borrero, Blanca, Gaudet, Alexandre, Poissy, Julien, Morel, Pascal, Richard, Pascale, Cognasse, Fabrice, Troya, Jesu, Trouillet-Assant, Sophie, Belot, Alexandre, Saker, Kahina, Garçon, Pierre, Rivière, Jacques G, Lagier, Jean-Christophe, Gentile, Stéphanie, Rosen, Lindsey B, Shaw, Elana, Morio, Tomohiro, Tanaka, Junko, Dalmau, David, Tharaux, Pierre-Loui, Sene, Damien, Stepanian, Alain, Megarbane, Bruno, Triantafyllia, Vasiliki, Fekkar, Arnaud, Heath, James R, Franco, José Lui, Anaya, Juan-Manuel, Solé-Violán, Jordi, Imberti, Luisa, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Delmonte, Ottavia M, Zhang, Yu, Snow, Andrew L, Holland, Steven M, Biggs, Catherine, Moncada-Vélez, Marcela, Arias, Andrés Augusto, Lorenzo, Lazaro, Boucherit, Soraya, Coulibaly, Boubacar, Anglicheau, Dany, Planas, Anna M, Haerynck, Filomeen, Duvlis, Sotirija, Nussbaum, Robert L, Ozcelik, Tayfun, Keles, Sevgi, Bousfiha, Ahmed A, El Bakkouri, Jalila, Ramirez-Santana, Carolina, Paul, Stéphane, Pan-Hammarström, Qiang, Hammarström, Lennart, Dupont, Annabelle, Kurolap, Alina, Metz, Christine N, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Ciceri, Fabio, Barreiros, Lucila A, Dominguez-Garrido, Elena, Vidigal, Mateu, Zatz, Mayana, van de Beek, Diederik, Sahanic, Sabina, Tancevski, Ivan, Stepanovskyy, Yurii, Boyarchuk, Oksana, Nukui, Yoko, Tsumura, Miyuki, Vidaur, Loreto, Tangye, Stuart G, Burrel, Sonia, Duffy, Darragh, Quintana-Murci, Llui, Klocperk, Adam, Kann, Nelli Y, Shcherbina, Anna, Lau, Yu-Lung, Leung, Daniel, Coulongeat, Matthieu, Marlet, Julien, Koning, Rutger, Reyes, Luis Felipe, Chauvineau-Grenier, Angélique, Venet, Fabienne, Monneret, Guillaume, Nussenzweig, Michel C, Arrestier, Romain, Boudhabhay, Idri, Baris-Feldman, Hagit, Hagin, David, Wauters, Joost, Meyts, Isabelle, Dyer, Adam H, Kennelly, Sean P, Bourke, Nollaig M, Halwani, Rabih, Sharif-Askari, Narjes Saheb, Dorgham, Karim, Sallette, Jérome, Sedkaoui, Souad Mehlal, Alkhater, Suzan, Rigo-Bonnin, Raúl, Morandeira, Francisco, Roussel, Lucie, Vinh, Donald C, Ostrowski, Sisse Rye, Condino-Neto, Antonio, Prando, Carolina, Bonradenko, Anastasiia, Spaan, András N, Gilardin, Laurent, Fellay, Jacque, Lyonnet, Stanisla, Bilguvar, Kaya, Lifton, Richard P, Mane, Shrikant, Anderson, Mark S, Boisson, Bertrand, Béziat, Vivien, Zhang, Shen-Ying, Vandreakos, Evangelo, Hermine, Olivier, Pujol, Aurora, Peterson, Pärt, Mogensen, Trine H, Rowen, Lee, Mond, Jame, Debette, Stéphanie, de Lamballerie, Xavier, Duval, Xavier, Mentré, France, Zins, Marie, Soler-Palacin, Pere, Colobran, Roger, Gorochov, Guy, Solanich, Xavier, Susen, Sophie, Martinez-Picado, Javier, Raoult, Didier, Vasse, Marc, Gregersen, Peter K, Piemonti, Lorenzo, Rodríguez-Gallego, Carlo, Notarangelo, Luigi D, Su, Helen C, Kisand, Kai, Okada, Satoshi, Puel, Anne, Jouanguy, Emmanuelle, Rice, Charles M, Tiberghien, Pierre, Zhang, Qian, Cobat, Aurélie, Abel, Laurent, Casanova, Jean-Laurent, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hiroshima University, Vall d’Hebron Research Institute (VHIR), University of Tartu, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor [Créteil], Service de Réanimation Médicale [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Members of the The Milieu Intérieur Consortium: Laurent Abel1 , Andres Alcover2 , Hugues Aschard2 , Philippe Bousso2 , Nollaig Bourke3 , Petter Brodin4 , Pierre Bruhns2 , Nadine Cerf-Bensussan5 , Ana Cumano2 , Christophe D’Enfert2 , Ludovic Deriano2 , Marie-Agnès Dillies2 , James Di Santo2 , Françoise Dromer2 , Gérard Eberl2 , Jost Enninga2 , Jacques Fellay6 , Ivo Gomperts-Boneca2 , Milena Hasan2 , Gunilla Karlsson Hedestam4 , Serge Hercberg7 , Molly A. Ingersoll2 , Olivier Lantz8 , Rose Anne Kenny3 , Mickaël Ménager5 , Frédérique Michel2 , Hugo Mouquet2 , Cliona O’Farrelly3 , Etienne Patin2 , Sandra Pellegrini2 , Antonio Rausell5 , Frédéric Rieux-Laucat5 , Lars Rogge2 , Magnus Fontes9 , Anavaj Sakuntabhai2 , Olivier Schwartz2 , Benno Schwikowski2 , Spencer Shorte2 , Frédéric Tangy2 , Antoine Toubert10 , Mathilde Touvier12 , Marie-Noëlle Ungeheuer2 , Christophe Zimmer2 , Matthew L. Albert11 , Darragh Duffy2 , Lluis Quintana-Murc, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 824110,H2020-INFRAIA-2018-1,EASI-Genomics(2019), European Project: 948959,ERC-2020-STG,MORE2ADA2(2021), National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Ministère des Solidarités et de la Santé (France), National Health and Medical Research Council (Australia), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Michailidis, Eleftherios, García-Prat, Marina, Paul, Stephanie, Metz, Christine N., Barreiros, Lucila, Domínguez-Garrido, Elena, Vidigal, Mateus, Beek, 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Pathology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Complex Trait Genetics, ACS - Diabetes & metabolism, Amsterdam Cardiovascular Sciences, Radiology and nuclear medicine, AMS - Rehabilitation & Development, VU University medical center, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Neuroinfection & -inflammation, Anesthesiology, APH - Quality of Care, ACS - Heart failure & arrhythmias, Özçelik, Tayfun, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, HUS Inflammation Center, Admin, Oskar, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères - - GENVIR2020 - ANR-20-CE93-0003 - AAPG2020 - VALID, Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19. - - AABIFNCOV2020 - ANR-20-CO11-0001 - COVID-19 - VALID, Program Initiative d’Excellence - IdEx Bordeaux (ANR-10-IDEX- 003-02) - INCOMING, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), École pratique des hautes études (EPHE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre 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Eto, S, Garcia-Prat, M, Bizien, L, Parra-Martínez, A, Yang, R, Haljasmägi, L, Migaud, M, Särekannu, K, Maslovskaja, J, de Prost, N, Tandjaoui-Lambiotte, Y, Luyt, C, Amador-Borrero, B, Gaudet, A, Poissy, J, Morel, P, Richard, P, Cognasse, F, Troya, J, Trouillet-Assant, S, Belot, A, Saker, K, Garçon, P, Rivière, J, Lagier, J, Gentile, S, Rosen, L, Shaw, E, Morio, T, Tanaka, J, Dalmau, D, Tharaux, P, Sene, D, Stepanian, A, Megarbane, B, Triantafyllia, V, Fekkar, A, Heath, J, Franco, J, Anaya, J, Solé-Violán, J, Imberti, L, Biondi, A, Bonfanti, P, Castagnoli, R, Delmonte, O, Zhang, Y, Snow, A, Holland, S, Biggs, C, Moncada-Vélez, M, Arias, A, Lorenzo, L, Boucherit, S, Coulibaly, B, Anglicheau, D, Planas, A, Haerynck, F, Duvlis, S, Nussbaum, R, Ozcelik, T, Keles, S, Bousfiha, A, El Bakkouri, J, Ramirez-Santana, C, Paul, S, Pan-Hammarström, Q, Hammarström, L, Dupont, A, Kurolap, A, Metz, C, Aiuti, A, Casari, G, Lampasona, V, Ciceri, F, Barreiros, L, Dominguez-Garrido, E, Vidigal, M, Zatz, M, van de Beek, D, Sahanic, S, Tancevski, I, Stepanovskyy, Y, Boyarchuk, O, Nukui, Y, Tsumura, M, Vidaur, L, Tangye, S, Burrel, S, Duffy, D, Quintana-Murci, L, Klocperk, A, Kann, N, Shcherbina, A, Lau, Y, Leung, D, Coulongeat, M, Marlet, J, Koning, R, Reyes, L, Chauvineau-Grenier, A, Venet, F, Monneret, G, Nussenzweig, M, Arrestier, R, Boudhabhay, I, Baris-Feldman, H, Hagin, D, Wauters, J, Meyts, I, Dyer, A, Kennelly, S, Bourke, N, Halwani, R, Sharif-Askari, N, Dorgham, K, Sallette, J, Sedkaoui, S, Alkhater, S, Rigo-Bonnin, R, Morandeira, F, Roussel, L, Vinh, D, Ostrowski, S, Condino-Neto, A, Prando, C, Bonradenko, A, Spaan, A, Gilardin, L, Fellay, J, Lyonnet, S, Bilguvar, K, Lifton, R, Mane, S, Anderson, M, Boisson, B, Béziat, V, Zhang, S, Vandreakos, E, Hermine, O, Pujol, A, Peterson, P, Mogensen, T, Rowen, L, Mond, J, Debette, S, de Lamballerie, X, Duval, X, Mentré, F, Zins, M, Soler-Palacin, P, Colobran, R, Gorochov, G, Solanich, X, Susen, S, Martinez-Picado, J, Raoult, D, Vasse, M, Gregersen, P, Piemonti, L, Rodríguez-Gallego, C, Notarangelo, L, Su, H, Kisand, K, Okada, S, Puel, A, Jouanguy, E, Rice, C, Tiberghien, P, Zhang, Q, Cobat, A, Abel, L, Casanova, J, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank Investigators, COVID Human Genetic Effort, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement du Sang study group, Bigio, B., Boucherit, S., de la Chapelle, A., Chen, J., Chrabieh, M., Coulibaly, B., Liu, D., Nemirowskaya, Y., Cruz, I.M., Materna, M., Pelet, S., Seeleuthner, Y., Thibault, C., Liu, Z., Abad, J., Accordino, G., Achille, C., Aguilera-Albesa, S., Aguiló-Cucurull, A., Aiuti, A., Özkan, E.A., Darazam, I.A., Roblero Albisures, J.A., Aldave, J.C., Ramos, M.A., Khan, T.A., Aliberti, A., Nadji, S.A., Alkan, G., Alkhater, S.A., Allardet-Servent, J., Allende, L.M., Alonso-Arias, R., Alshahrani, M.S., Alsina, L., Alyanakian, M.A., Borrero, B.A., Amoura, Z., Antolí, A., Arrestier, R., Aubart, M., Auguet, T., Avramenko, I., Aytekin, G., Azot, A., Bahram, S., Bajolle, F., Baldanti, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Barzagh, F., Basso, S., Bayhan, G.I., Belot, A., Bezrodnik, L., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blázquez-Gamero, D., Bleibtreu, A., Bloomfield, M., Bolivar-Prados, M., Bondarenko, A., Borghesi, A., Borie, R., Botdhlo-Nevers, E., Bousfiha, A.A., Bousquet, A., Boutolleau, D., Bouvattier, C., Boyarchuk, O., Bravais, J., Briones, M.L., Brunner, M.E., Bruno, R., Bueno, MRP, Bukhari, H., Bustamante, J., Cáceres Agra, J.J., Capra, R., Carapito, R., Carrabba, M., Casari, G., Casasnovas, C., Caseris, M., Cassaniti, I., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Celik, J.B., Ceschi, A., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Cohen, Y., Colobran, R., Comarmond, C., Combes, A., Comoli, P., Corsico, A.G., Coşkuner, T., Cvetkovski, A., Cyrus, C., Dalmau, D., Danion, F., Darley, D.R., Das, V., Dauby, N., Dauger, S., De Munter, P., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Desguerre, I., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Domínguez-Garrido, E., Dubost, C., Ekwall, O., Bozdemir, Ş.E., Elnagdy, M.H., Emiroglu, M., Endo, A., Erdeniz, E.H., Aytekin, S.E., Lasa, MPE, Euvrard, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Ferrer, R., Ferreres, J., Flores, C., Francois, B., Fumadó, V., Fung, KSC, Fusco, F., Gagro, A., Solis, B.G., Gaussem, P., Gayretli, Z., Gil-Herrera, J., Gilardin, L., Gatineau, A.G., Girona-Alarcón, M., Cifuentes Godínez, K.A., Goffard, J.C., Gonzales, N., Gonzalez-Granado, L.I., González-Montelongo, R., Guerder, A., Gülhan, B., Gumucio, V.D., Hanitsch, L.G., Gunst, J., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hancerli, S., Hariyan, T., Hatipoglu, N., Heppekcan, D., Hernandez-Brito, E., Ho, P.K., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Hung, IFN, Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jimeno, M.T., Jordan, I., Yüksek, S.K., Kara, Y.B., Karahan, A., Karbuz, A., Yasar, K.K., Kasapcopur, O., Kashimada, K., Keles, S., Demirkol, Y.K., Kido, Y., Kizil, C., Kılıç, A.O., Klocperk, A., Koutsoukou, A., Król, Z.J., Ksouri, H., Kuentz, P., Kwan, AMC, Kwan, YWM, Kwok, JSY, Lagier, J.C., Lam, DSY, Lampropoulou, V., Lanternier, F., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Lilleri, D., Lima, EJAB, Linglart, A., López-Collazo, E., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Lung, K.C., Luyt, C.E., Lye, D.C., Magnone, C., Mansouri, D., Marchioni, E., Marioli, C., Marjani, M., Marques, L., Pereira, J.M., Martín-Nalda, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mata-Martínez, C., Mathian, A., Matos, L.R., Matthews, G.V., Mayaux, J., McLaughlin-Garcia, R., Meersseman, P., Mège, J.L., Mekontso-Dessap, A., Melki, I., Meloni, F., Meritet, J.F., Merlani, P., Akcan, Ö.M., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Million, M., Mirault, T., Mircher, C., Mirsaeidi, M., Mizoguchi, Y., Modi, B.P., Mojoli, F., Moncomble, E., Melián, A.M., Martinez, A.M., Morandeira, F., Morange, P.E., Mordacq, C., Morelle, G., Mouly, S.J., Muñoz-Barrera, A., Nafati, C., Nagashima, S., Nakagama, Y., Neven, B., Neves, J.F., Ng, L.F., Ng, Y.Y., Nielly, H., Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Okamoto, K., Oualha, M., Ouedrani, A., Özçelik, T., Ozkaya-Parlakay, A., Pagani, M., Pan-Hammarström, Q., Papadaki, M., Parizot, C., Parola, P., Pascreau, T., Paul, S., Paz-Artal, E., Pedraza, S., González Pellecer, N.C., Pellegrini, S., de Diego, R.P., Pérez-Fernández, X.L., Philippe, A., Philippot, Q., Picod, A., de Chambrun, M.P., Piralla, A., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Poulakou, G., Pouletty, M.S., Pourshahnazari, P., Qiu-Chen, J.L., Quentric, P., Rambaud, T., Raoult, D., Raoult, V., Rebillat, A.S., Redin, C., Resmini, L., Ricart, P., Richard, J.C., Rigo-Bonnin, R., Rivet, N., Rivière, J.G., Rocamora-Blanch, G., Rodero, M.P., Rodrigo, C., Rodriguez, L.A., Rodriguez-Gallego, C., Rodriguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Roux, D., Rovina, N., Rozenberg, F., Ruch, Y., Ruiz, M., Ruiz Del Prado, M.Y., Ruiz-Rodriguez, J.C., Sabater-Riera, J., Saks, K., Salagianni, M., Sanchez, O., Sánchez-Montalvá, A., Sánchez-Ramón, S., Schidlowski, L., Schluter, A., Schmidt, J., Schmidt, M., Schuetz, C., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L., Seminario, A.G., Sene, D., Seng, P., Senoglu, S., Seppänen, M., Llovich, A.S., Shahrooei, M., Shcherbina, A., Siguret, V., Siouti, E., Smadja, D.M., Smith, N., Sobh, A., Solanich, X., Solé-Violán, J., Soler, C., Soler-Palacín, P., Sözeri, B., Stella, G.M., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Tello, L.V., Terrier, B., Thiery, G., Thorball, C., Thorn, K., Thumerelle, C., Tipu, I., Tolstrup, M., Tomasoni, G., Toubiana, J., Alvarez, J.T., Triantafyllia, V., Trouillet-Assant, S., Troya, J., Tsang, OTY, Tserel, L., Tso, EYK, Tucci, A., Tüter Öz, Ş.K., Ursini, M.V., Utsumi, T., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Den Rym, A.M., Vandernoot, I., Velez-Santamaria, V., Zuniga Veliz, S.P., Vidigal, M.C., Viel, S., Vilain, C., Vilaire-Meunier, M.E., Villar-García, J., Vincent, A., Vogt, G., Voiriot, G., Volokha, A., Vuotto, F., Wauters, E., Wauters, J., Wu, AKL, Wu, T.C., Yahşi, A., Yesilbas, O., Yildiz, M., Young, B.E., Yükselmiş, U., Zatz, M., Zecca, M., Zuccaro, V., Jens, V.P., Lambrecht, B.N., Eva, V.B., Cédric, B., Levi, H., Eric, H., Bauters, F., De Clercq, J., Cathérine, H., Hans, S., Leslie, N., Florkin, B., Boulanger, C., Vanderlinden, D., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Danielson, J.J., Dobbs, K., Kashyap, A., Ding, L., Dalgard, C.L., Sottini, A., Quaresima, V., Quiros-Roldan, E., Rossi, C., Bettini, L.R., D'Angio', M., Beretta, I., Montagna, D., Licari, A., Marseglia, G.L., Batten, I., Reddy, C., McElheron, M., Noonan, C., Connolly, E., Fallon, A., Storgaard, M., Jørgensen, S., Erikstrup, C., Pedersen, O.B., Sørensen, E., Mikkelsen, S., Dinh, K.M., Larsen, MAH, Paulsen, I.W., Von Stemann, J.H., Hansen, M.B., Ostrowski, S.R., Townsend, L., Cheallaigh, C.N., Bergin, C., Martin-Loeches, I., Dunne, J., Conlon, N., Bourke, N., O'Farrelly, C., Abel, L., Allavena, C., Andrejak, C., Angoulvant, F., Azoulay, C., Bachelet, D., Bartoli, M., Basmaci, R., Behilill, S., Beluze, M., Benech, N., Benkerrou, D., Bhavsar, K., Bitker, L., Bouadma, L., Bouscambert-Duchamp, M., Paz, P.C., Cervantes-Gonzalez, M., Chair, A., Chirouze, C., Coelho, A., Cordel, H., Couffignal, C., Couffin-Cadiergues, S., d'Ortenzio, E., De Montmollin, E., Debard, A., Debray, M.P., Deplanque, D., Descamps, D., Desvallée, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V., Epaulard, O., Esperou, H., Esposito-Farese, M., Etienne, M., Garot, D., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gilg, M., Goehringer, F., Guedj, J., Hoctin, A., Hoffmann, I., Houas, I., Hulot, J.S., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Kerroumi, Y., Khalil, A., Khan, C., Kimmoun, A., Laine, F., Laouénan, C., Laribi, S., Le, M., Le Bris, C., Le Gac, S., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lemaignen, A., Lemee, V., Lescure, F.X., Letrou, S., Levy, Y., Lina, B., Lingas, G., Lucet, J.C., Machado, M., Malvy, D., Mambert, M., Manuel, A., Mentré, F., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Nguyen, D., Noret, M., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Peigne, V., Petrov-Sanchez, V., Peytavin, G., Pham, H., Picone, O., Piquard, V., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Su, R., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Tual, C., Tubiana, S., Van Der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Annereau, J.P., Briseño-Roa, L., Gribouval, O., Pelet, A., Alcover, A., Aschard, H., Bousso, P., Brodin, P., Bruhns, P., Cerf-Bensussan, N., Cumano, A., D'Enfert, C., Deriano, L., Dillies, M.A., Di Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hedestam, G.K., Hercberg, S., Ingersoll, M.A., Lantz, O., Kenny, R.A., Ménager, M., Michel, F., Patin, E., Rausell, A., Rieux-Laucat, F., Rogge, L., Fontes, M., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Zimmer, C., Albert, M.L., Duffy, D., Quintana-Murci, L., Alavoine, L., Behillil, S., Burdet, C., Charpentier, C., Dechanet, A., Ecobichon, J.L., Frezouls, W., Houhou, N., Lehacaut, J., Manchon, P., Nouroudine, M., Quintin, C., Thy, M., van der Werf, S., Vignali, V., Chahine, A., Waucquier, N., Migaud, M.C., Djossou, F., Mergeay-Fabre, M., Lucarelli, A., Demar, M., Bruneau, L., Gérardin, P., Maillot, A., Payet, C., Laviolle, B., Paris, C., Desille-Dugast, M., Fouchard, J., Pistone, T., Perreau, P., Gissot, V., Le Goas, C., Montagne, S., Richard, L., Bouiller, K., Desmarets, M., Meunier, A., Lefévre, B., Jeulin, H., Legrand, K., Lomazzi, S., Tardy, B., Gagneux-Brunon, A., Bertholon, F., Botelho-Nevers, E., Kouakam, C., Leturque, N., Roufai, L., Amat, K., Espérou, H., Hendou, S., van Agtmael, M., Algera, A.G., Appelman, B., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bonta, P., Bos, L., Botta, M., de Brabander, J., de Bree, G., de Bruin, S., Buis, DTP, Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Dijkstra, M., Dongelmans, D.A., Dujardin, RWG, Elbers, P., Fleuren, L., Geijtenbeek, SGT, Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., Lim, EHT, van Mourik, N., Nellen, J., Nossent, E.J., Paulus, F., Peters, E., Pina-Fuentes, DAI, van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., de Rotte, MCFJ, Schinkel, M., Schultz, M.J., Schrauwen, FAP, Schuurmans, A., Schuurmans, J., Sigaloff, K., Slim, M.A., Smeele, P., Smit, M., Stijnis, C.S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A.M., Tuinman, P.R., van der Valk, M., Veelo, D., Volleman, C., de Vries, H., Vught, L.A., van Vugt, M., Wouters, D., Zwinderman, AHK, Brouwer, M.C., Wiersinga, W.J., Vlaar, APJ, van de Beek, D., Al-Muhsen, S., Al-Mulla, F., Anderson, M.S., Andreakos, E., Arias, A.A., Biggs, C.M., Bogunovic, D., Bolze, A., Bryceson, Y., Bustamante, C.D., Butte, M.J., Chakravorty, S., Christodoulou, J., Condino-Neto, A., Constantinescu, S.N., Cooper, M.A., Desai, M., Drolet, B.A., El Baghdadi, J., Espinosa-Padilla, S., Franco, J.L., Froidure, A., Gregersen, P.K., Hagin, D., Heath, J.R., Henrickson, S.E., Hsieh, EWY, Husebye, E.S., Imai, K., Itan, Y., Jarvis, E.D., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Maródi, L., Milner, J.D., Mironska, K., Mogensen, T.H., Morio, T., Ng, LFP, Notarangelo, L.D., Novelli, A., Novelli, G., Okada, S., Ozcelik, T., Planas, A.M., Prando, C., Pujol, A., Renia, L., Resnick, I., Rodríguez-Gallego, C., Sancho-Shimizu, V., Seppänen, MRJ, Slaby, O., Snow, A.L., Spaan, A.N., Tancevski, I., Tangye, S.G., Abou Tayoun, A., Ramaswamy, S., Turvey, S.E., Uddin, KMF, Uddin, M.J., Vinh, D.C., von Bernuth, H., Zawadzki, P., Su, H.C., Casanova, J.L., Nadif, R., Goldberg, M., Ozguler, A., Henny, J., Lemonnier, S., Coeuret-Pellicer, M., Le Got, S., Zins, M., Tzourio, C., Debette, S., Dufouil, C., Soumaré, A., Lachaize, M., Fievet, N., Flaig, A., Martin, F., Bonneaudeau, B., Cannet, D., Gallian, P., Jeanne, M., Perroquin, M., Hamzeh-Cognasse, H., Bastard, Paul [0000-0002-5926-8437], Gervais, Adrian [0000-0002-1083-5787], Le Voyer, Tom [0000-0002-0630-8626], Rosain, Jérémie [0000-0002-2822-161X], Manry, Jérémy [0000-0001-5998-2051], Michailidis, Eleftherios [0000-0002-9907-4346], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Eto, Shohei [0000-0002-2885-7490], García-Prat, Marina [0000-0001-5387-1908], Bizien, Lucy [0000-0001-9163-9122], Parra-Martínez, Alba [0000-0002-9564-8912], Dorgham, Karim [0000-0001-9539-3203], Alkhater, Suzan [0000-0001-7315-6581], Rigo-Bonnin, Raúl [0000-0001-5511-074X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Ostrowski, Sisse Rye [0000-0001-5288-3851], Condino-Neto, Antonio [0000-0002-1069-3117], Prando, Carolina [0000-0002-9570-9770], Spaan, András N. [0000-0001-5981-7259], Gilardin, Laurent [0000-0001-9212-0859], Yang, Rui [0000-0003-4427-2158], Fellay, Jacques [0000-0002-8240-939X], Bilguvar, Kaya [0000-0002-7313-7652], Mane, Shrikant M. [0000-0002-3267-5139], Anderson, MarK S. [0000-0002-3093-4758], Boisson, Bertrand [0000-0001-5240-3555], Béziat, Vivien [0000-0002-4020-824X], Andreakos, Evangelos [0000-0001-5536-1661], Hermine, Olivier [0000-0003-2574-3874], Pujol, Aurora [0000-0002-9606-0600], Peterson, Pärt [0000-0001-6755-791X], Haljasmägi, Liis [0000-0001-7162-9808], Mogensen, Trine [0000-0002-1853-9704], Lamballerie, Xavier de [0000-0001-7895-2720], Zins, Marie [0000-0002-4540-4282], Soler-Palacín, Pere [0000-0002-0346-5570], Colobran, Roger [0000-0002-5964-536X], Gorochov, Guy [0000-0003-2097-9677], Solanich, Xavier [0000-0002-2572-2187], Susen, Sophie [0000-0001-5953-163X], Martínez-Picado, Javier [0000-0002-4916-2129], Gregersen, Peter K. [0000-0003-1613-1518], Migaud, Mélanie [0000-0003-3062-1214], Piemonti, Lorenzo [0000-0002-2172-2198], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Notarangelo, Luigi D. [0000-0002-8335-0262], Su, Helen C. [0000-0002-5582-9110], Kisand, Kai [0000-0002-5426-4648], Okada, Satoshi [0000-0002-4622-5657], Puel, Anne [0000-0003-2603-0323], Jouanguy, Emmanuelle [0000-0002-7358-9157], Tiberghien, Pierre [0000-0002-9310-8322], Zhang, Qian [0000-0002-9040-3289], Särekannu, Karita [0000-0002-5984-668X], Cobat, Aurélie [0000-0001-7209-6257], Abel, Laurent [0000-0001-7016-6493], Casanova, Jean-Laurent [0000-0002-7782-4169], Prost, Nicolas de [0000-0002-4833-4320], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Luyt, Charles-Edouard [0000-0001-7424-2705], Amador-Borrero, Blanco [0000-0001-6170-8721], Poissy, Julien [0000-0001-6017-5353], Richard, Pascale [0000-0003-1864-3824], Cognasse, Fabrice [0000-0001-8041-928X], Troya, Jesús [0000-0001-7323-114X], Trouillet-Assant, Sophie [0000-0001-6439-4705], Belot, Alexandre [0000-0003-4902-5332], Saker, Kahina [0000-0001-8825-5400], Rivière, Jacques G. [0000-0003-1055-2063], Gentile, Stephanie [0000-0003-3858-9503], Rosen, Lindsey B. [0000-0001-5894-3878], Shaw, Elana [0000-0001-9265-8026], Dalmau, David [0000-0003-1936-478X], Tharaux, Pierre-Louis [0000-0002-6062-5905], Stépanian, Alain [0000-0002-2942-0901], Mégarbane, Bruno [0000-0002-2522-2764], Triantafyllia, Vasiliki [0000-0001-5832-4014], Fekkar, Arnaud [0000-0001-9954-075X], Heath, James R. [0000-0001-5356-4385], Franco, José Luis [0000-0001-5664-6415], Anaya, Juan Manuel [0000-0002-6444-1249], Imberti, Luisa[0000-0002-2075-8391], Bonfanti, Paolo [0000-0001-7289-8823], Castagnoli, Riccardo [0000-0003-0029-9383], Snow, Andrew L. [0000-0002-8728-6691], Holland, Steven M. [0000-0003-3207-5464], Biggs, Catherine M. [0000-0002-4363-2660], Moncada-Velez, Marcela [0000-0002-3073-5345], Arias, Andrés Augusto [0000-0002-9478-8403], Lorenzo, Lazaro [0000-0001-6648-8684], Boucherit, Soraya [0000-0002-8819-7594], Anglicheau, Dany [0000-0001-5793-6174], Planas, Anna M. [0000-0002-6147-1880], Haerynck, Filomeen [0000-0001-9161-7361], Duvlis, Sotirija [0000-0001-8587-7386], Nussbaum, Robert [0000-0003-3445-8880], Bousfiha, Ahmed Aziz [0000-0002-5011-9873], El Bakkouri, Jalila [0000-0003-2303-3369], Ramírez-Santana, Carolina [0000-0003-2137-4899], Paul, Stephanie [0000-0002-8830-4273], Pan-Hammarström, Qiang [0000-0003-1990-8804], Hammarström, Lennart [0000-0002-8635-9609], Dupont, Annabelle [0000-0002-1554-9931], Kurolap, Alina [0000-0002-7005-3621], Metz, Christine N. [0000-0002-1013-1691], Aiuti, Alessandro [0000-0002-5398-1717], Casari, Giorgio [0000-0002-0115-8980], Lampasona, Vito [0000-0001-5162-8445], Ciceri, Fabio [0000-0003-0873-0123], Barreiros, Lucila [0000-0002-9818-2345], Domínguez-Garrido, Elena [0000-0002-2066-0511], Vidigal, Mateus [0000-0002-8895-652X], Zatz, Mayana [0000-0003-3970-8025], Beek, Diederik van der [0000-0002-4571-044X], Stepanovskyy, Yuriy [0000-0001-6339-5490], Boyarchuk, Oksana [0000-0002-1234-0040], Nukui, Yoko [0000-0002-6123-5212], Vidaur, Loreto [0000-0002-6720-4900], Tangye, Stuart G. [0000-0002-5360-5180], Burrel, Sonia [0000-0002-7783-2601], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Klocperk, Adam [0000-0002-1526-4557], Kan, Nelli [0000-0003-3564-6496], Shcherbina, Anna [0000-0002-3113-4939], Lau, Yu-Lung [0000-0002-4780-0289], Leung, Daniel [0000-0002-9360-6233], Coulongeat, Matthieu [0000-0003-1986-3546], Marlet, Julien [0000-0002-8645-8703], Koning, Rutger [0000-0003-3128-5072], Reyes, Luis Felipe [0000-0003-1172-6539], Venet, Fabienne [0000-0003-0462-4235], Monneret, Guillaume [0000-0002-9961-5739], Nussenzweig, Michel C. [0000-0003-0592-8564], Baris, Hagit N. [0000-0003-4065-7560], Hagin, David [0000-0003-2702-1031], Wauters, Joost [0000-0002-5983-3897], Meyts, Isabelle [0000-0003-1214-0302], Dyer, Adam [0000-0003-1356-510X], Bourke, Nollaig [0000-0003-4313-6859], Halwani, Rabih [0000-0002-6516-7771], and Sharif-Askari, Narjes Saheb [0000-0003-0482-6777]
Subjects: Interferon Type I/immunology, AUTOIMMUNITY, [SDV]Life Sciences [q-bio], Interferó, Gastroenterology, COVID-19 (Malaltia), Immunoglobulin G, Basic medicine, 0302 clinical medicine, Medicine and Health Sciences, 80 and over, Immunologia, Young adult, Child, Neutralizing, MYASTHENIA-GRAVIS PATIENTS, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, biology, General Medicine, Middle Aged, 3. Good health, COVID-19/immunology, Settore MED/03, 030220 oncology & carcinogenesis, Child, Preschool, Interferon Type I, Antibody, medicine.symptom, INTERFERON, Adult, medicine.medical_specialty, Adolescent, Critical Illness, Immunology, Population, Aged, Antibodies, Neutralizing, Autoantibodies, COVID-19, Case-Control Studies, Humans, Infant, Infant, Newborn, Interferon-alpha, Young Adult, Alpha interferon, Immunoglobulins, IMMUNITY, Asymptomatic, PATIENT, 03 medical and health sciences, Internal medicine, medicine, Preschool, education, Antibodies, Neutralizing/blood, HOMENS, 030304 developmental biology, ANTINUCLEAR, business.industry, Autoantibody, Case-control study, Antibodies, Neutralizing/immunology, Autoantibodies/blood, Autoantibodies/immunology, COVID-19/mortality, Immunoglobulin G/blood, Immunoglobulin G/immunology, Interferon-alpha/immunology, Newborn, DISTINCT FUNCTIONS, ALPHA, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Immunoglobulines
Abstract: Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Awards (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Yale High Performance Computing Center (S10OD018521), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), ANR GENVIR (ANR-20-CE93-003) and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 824110 (EASI-Genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’Enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University of Paris. P.B. was supported by the FRM (EA20170638020). P.B., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt Schueller). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the NIAID and NIDCR, NIH (grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (reference ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (AJF202019), Dubai, UAE, and a COVID-19 research grant (CoV19-0307) from the University of Sharjah, UAE. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a UNSW Sydney COVID Rapid Response Initiative Grant. L.I. reported funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). L.I. and G. L. Marseglia reported funding from Regione Lombardia, Italy (project Risposta immune in pazienti con COVID-19 e co-morbidità). This research was partially supported by the Instituto de Salud Carlos III (COV20/0968). J.R.H. reported funding from Biomedical Advanced Research and Development Authority HHSO10201600031C. S.O. reports funding Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development, AMED (grant number JP20fk0108531). G.G. was supported by ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The Three-City (3C) Study was conducted under a partnership agreement among the INSERM, the Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques”. S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under contract no. 75N91019D00024, task order no. 75N91021F00001. J.W. is supported by an FWO Fundamental Clinical Mandate (1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF). C.R.-G. and colleagues of the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017 and OA20/024), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). C.M.B. is supported by a MSFHR Health Professional-Investigator Award. P.Q.H. and L.H. were funded by the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX (806-2018) and Colciencias contract 713-2016 (code 111574455633)]. A.K. was in part supported by grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies; by the KU Leuven C1 grant C16/18/007; by a VIB-GC PID grant; by the FWO frants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). M.Vi received funding from the São Paulo Research Foundation (FAPESP) (grant number 2020/09702-1) and JBS SA (grant number 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation
Published: 2021

5. Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus

Author: Cecilia Hellström, A. G. Frostegård, Peter Nilsson, Johan Frostegård, Sofia Ajeganova, Clinical sciences, and Rheumatology
Subjects: Carotid Artery Diseases, Male, 0301 basic medicine, alpha-Crystallin B Chain/immunology, Disease, Autoantigens, Carotid Intima-Media Thickness, Carotid Artery Diseases/blood, Basic Helix-Loop-Helix Transcription Factors, Lupus Erythematosus, Systemic, Medicine, Medicine(all), biology, Carotid Artery, Common/diagnostic imaging, Middle Aged, Prognosis, Plaque, Atherosclerotic, Phenotype, Protein microarray, Female, Antibody, Adult, Carotid Artery, Common, Protein Array Analysis, Lupus Erythematosus, Systemic/blood, 03 medical and health sciences, Rheumatology, Antigen, Autoantigens/immunology, Predictive Value of Tests, Humans, Carrier Proteins/immunology, Autoantibodies, business.industry, Autoantibody, alpha-Crystallin B Chain, 030104 developmental biology, Immunoglobulin G/blood, Basic Helix-Loop-Helix Transcription Factors/immunology, Case-Control Studies, Immunoglobulin G, Immunology, biology.protein, B-Cell Activation Factor Receptor/immunology, Autoantibodies/blood, Carrier Proteins, business, Biomarkers/blood, Biomarkers, B-Cell Activation Factor Receptor
Abstract: Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20–140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients ( n = 107) and age- and sex-matched population-based controls ( n = 107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.
Published: 2018

6. PERFORMANCE OF SMARTPHONE-BASED DIGITAL IMAGES FOR CERVICAL CANCER SCREENING IN A LOW-RESOURCE CONTEXT

Author: Pierre Vassilakos, Phuong Lien Tran, Josea Lea Herinianasolo, Caroline Benski, Christophe Combescure, Jeromine Jinoro, Manuela Viviano, and Patrick Petignat
Subjects: Adult, medicine.medical_specialty, Uterine Cervical Neoplasms, Antinuclear/blood, Context (language use), Cervical cancer screening, Sensitivity and Specificity, Antibodies, 03 medical and health sciences, Digital image, 0302 clinical medicine, 80 and over, Neutrophils/immunology/pathology, Madagascar, medicine, Humans, Medical physics, 030212 general & internal medicine, Pleural Effusion/diagnosis/etiology/immunology/pathology, Early Detection of Cancer, Aged, Cervical cancer, ddc:618, Systemic/complications/diagnosis/immunology/pathology, Lupus Erythematosus, business.industry, Health Policy, Papillomavirus Infections, Online database, Gold standard (test), Uterine Cervical Dysplasia, medicine.disease, Confidence interval, Visual inspection, Pulmonary Eosinophilia/diagnosis/etiology/immunology/pathology, 030220 oncology & carcinogenesis, Female, Smartphone, Neoplasm Grading, Autoantibodies/blood, business
Abstract: Objectives:Colposcopes are expensive, heavy, and need specialized technical service, which may outreach the capacity of low-resource settings. Our aim was to assess the performance of smartphone-based digital images for the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).Methods:Human papillomavirus (HPV)-positive women recruited through a cervical cancer screening campaign had VIA/VILI assessment (visual inspection after application of acetic acid/lugol's iodine). Cervical digital images were captured with a smartphone camera, randomly coded with no prior selection and distributed on an online database (Google Forms) for evaluation. Healthcare providers were invited to evaluate the images and identify CIN2+. The gold standard was the histopathological diagnosis. The sensitivity and specificity for the detection of CIN2+ was assessed for each reader and reported with the 95 percent confidence interval (Clopper-Pearson method).Results:One hundred twenty-five consecutive HPV-positive women were included, with 19 CIN2+ (15.2 percent). Forty-five gynecologists completed the assessment, one-third were considered as experts (>50 colposcopies) and two-thirds as novices (Conclusion:Smartphone-based digital images, with its high portability, have a great potential for the diagnosis of CIN2+ in low-resource context.
Published: 2018

7. Impact of CD14 Polymorphisms on Anti-Apolipoprotein A-1 IgG-Related Coronary Artery Disease Prediction in the General Population

Author: Nathalie Satta, Peter Vollenweider, Fabrizio Montecucco, Pedro Marques-Vidal, François Mach, Zoltán Kutalik, Sabrina Pagano, Nicolas Vuilleumier, Gérard Waeber, Oliver Hartley, Julien Virzi, and Panagiotis Antiochos
Subjects: Male, 0301 basic medicine, Apolipoprotein A-I/immunology, Time Factors, Apolipoprotein B, Lipopolysaccharide Receptors, Coronary Artery Disease, Kaplan-Meier Estimate, ddc:616.07, 030204 cardiovascular system & hematology, medicine.disease_cause, Autoimmunity, Coronary artery disease, chemistry.chemical_compound, Switzerland/epidemiology, 0302 clinical medicine, Gene Frequency, apolipoprotein A-1, autoantibodies, cholesterol, coronary artery disease, risk stratification, CD14 polymorphism, HDL cholesterol, autoimmunity, Risk Factors, Prospective Studies, ddc:616, education.field_of_study, biology, Incidence, Homozygote, Middle Aged, Phenotype, Cardiology, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, Switzerland, Adult, Heterozygote, medicine.medical_specialty, CD14, Population, Polymorphism, Single Nucleotide, Risk Assessment, Coronary Artery Disease/blood/epidemiology/genetics/immunology, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, ddc:576, Lipopolysaccharide Receptors/genetics/immunology, education, Genetic Association Studies, Autoantibodies, Proportional Hazards Models, Chi-Square Distribution, Apolipoprotein A-I, Cholesterol, business.industry, Autoantibody, medicine.disease, Surgery, Institutional repository, 030104 developmental biology, chemistry, Immunoglobulin G/blood, Immunoglobulin G, Multivariate Analysis, biology.protein, Autoantibodies/blood, business, Biomarkers/blood, Biomarkers
Abstract: Objective— We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism. Approach and Results— In a prospectively studied, population-based cohort of 5220 subjects (mean age 52.6±10.7 years, 47.4% males), followed over a median period of 5.6 years, subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate of 3.9% versus 2.8% ( P =0.077) and a nonfatal CAD rate of 3.6% versus 2.3% ( P =0.018), respectively. After multivariate adjustment for established cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94–1.97; P =0.105) and hazard ratio=1.53 (95% confidence interval, 1.03–2.26; P =0.034), respectively. In subjects with available genetic data for the C260T rs2569190 single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a significant interaction between anti-apoA-1 IgG and rs2569190 allele status with regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total and nonfatal CAD in non-TT carriers, whereas being associated with the lowest risk for total and nonfatal CAD in TT homozygotes ( P for interaction =0.011 and P for interaction =0.033, respectively). Conclusions— Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene–autoantibody interaction for the development of CAD.
Published: 2017

8. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth:A Systematic Review and Meta-analysis

Author: Korevaar, Tim I.M., Derakhshan, Arash, Taylor, Peter N, Meima, Marcel, Chen, Liangmiao, Bliddal, Sofie, Carty, David M, Meems, Margreet, Vaidya, Bijay, Shields, Beverley, Ghafoor, Farkhanda, Popova, Polina V, Mosso, Lorena, Oken, Emily, Suvanto, Eila, Hisada, Aya, Yoshinaga, Jun, Brown, Suzanne J, Bassols, Judit, Auvinen, Juha, Bramer, Wichor M, López-Bermejo, Abel, Dayan, Colin, Boucai, Laura, Vafeiadi, Marina, Grineva, Elena N, Tkachuck, Alexandra S, Pop, Victor J M, Vrijkotte, T G, Guxens, M, Chatzi, L, Sunyer, J, Jiménez-Zabala, A, Riaño, I, Murcia, M, Lu, X, Mukhtar, S, Delles, C, Feldt-Rasmussen, U, Nelson, S M, Alexander, E K, Chaker, L, Männistö, T, Walsh, J P, Pearce, E N, Steegers, E A P, Peeters, R P, Korevaar, Tim I.M., Derakhshan, Arash, Taylor, Peter N, Meima, Marcel, Chen, Liangmiao, Bliddal, Sofie, Carty, David M, Meems, Margreet, Vaidya, Bijay, Shields, Beverley, Ghafoor, Farkhanda, Popova, Polina V, Mosso, Lorena, Oken, Emily, Suvanto, Eila, Hisada, Aya, Yoshinaga, Jun, Brown, Suzanne J, Bassols, Judit, Auvinen, Juha, Bramer, Wichor M, López-Bermejo, Abel, Dayan, Colin, Boucai, Laura, Vafeiadi, Marina, Grineva, Elena N, Tkachuck, Alexandra S, Pop, Victor J M, Vrijkotte, T G, Guxens, M, Chatzi, L, Sunyer, J, Jiménez-Zabala, A, Riaño, I, Murcia, M, Lu, X, Mukhtar, S, Delles, C, Feldt-Rasmussen, U, Nelson, S M, Alexander, E K, Chaker, L, Männistö, T, Walsh, J P, Pearce, E N, Steegers, E A P, and Peeters, R P
Abstract: Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The
Published: 2019

9. Reference limits for GAD65 and IA-2 autoantibodies by chemiluminescence immunoassay in Northern European adults and children

Author: Cindy Soendersoe Knudsen, Agnes Ziobrowska-Bech, Britta Kremke, Anne Winther-Larsen, and Tina Parkner
Subjects: Male, Luminescence, endocrine system diseases, Chemiluminescence immunoassay, Clinical Biochemistry, Gene Expression, 01 natural sciences, 0302 clinical medicine, immune system diseases, Reference Values, Healthy volunteers, antibodies, 030212 general & internal medicine, Child, Immunoassay, biology, Glutamate Decarboxylase, General Medicine, Middle Aged, Healthy Volunteers, Europe, Child, Preschool, diabetes mellitus, Female, Antibody, Adult, Adolescent, Immunoassay/standards, European Continental Ancestry Group, White People, Glutamate Decarboxylase/antagonists & inhibitors, paediatrics, 03 medical and health sciences, Diabetes mellitus, medicine, Humans, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Aged, Autoantibodies, Type 1 diabetes, Receptor-Like Protein Tyrosine Phosphatases, Class 8/antagonists & inhibitors, ICA512 autoantibody, business.industry, 010401 analytical chemistry, Autoantibody, Infant, Newborn, nutritional and metabolic diseases, Infant, Diabetes Mellitus, Type 1/blood, medicine.disease, 0104 chemical sciences, Diabetes Mellitus, Type 1, Reference values, GAD65, Immunology, biology.protein, business, Autoantibodies/blood, Biomarkers/blood, Biomarkers
Abstract: The GAD65 and IA-2 antibodies (Abs) are biomarkers of the development of type 1 diabetes mellitus (T1DM) in both children and adults. The upper reference limit for the autoantibodies made by the manufacture was established on an adult Chinese population. Here, we established upper reference limits for Northern European adults and children in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Serum samples from healthy Danish children (0–18 years) and adults (18–70 years) were analysed for GAD65Ab and IA-2Ab using MAGLUMI 800 Chemiluminescence Immunoassay (CLIA). The Kruskal–Wallis test was used for evaluating differences between gender and age groups. No gender or age differences were found for neither GAD65Ab nor IA-2Ab, and a combined upper reference limit for both children and adults could be established. An upper reference limit of 5.1 IU/mL was defined for GAD65Ab and 11.5 U/mL for IA-2Ab. Our results showed a substantial discrepancy with the reference limits established by the manufacturer.
Published: 2019

10. Phenotypes determined by cluster analysis and their survival in the prospective European Scleroderma Trials and Research cohort of patients with systemic sclerosis

Author: Sobanski, Vincent, Giovannelli, Jonathan, Allanore, Yannick, Riemekasten, Gabriela, Airo, Paolo, Vettori, Serena, Cozzi, Franco, Distler, Oliver, Matucci-Cerinic, Marco, Denton, Christopher, Launay, David, Hachulla, Eric, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Kyburz, Diego, Lapadula, Giovanni, Iannone, Florenzo, Maurer, Britta, Jordan, Suzana, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Siegert, Elise, Rednic, Simona, Nicoara, Ileana, Kahan, Andre, Vlachoyiannopoulos, Panayiotis, Montecucco, Carlo, Caporali, Roberto, Stork, Jiri, Inanc, Murat, Carreira, Patricia E, Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Kucharz, Eugene J, Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Wu, Chen, Marjanovic, Zora, Faivre, Helene, Hij, Darin, Dhamadi, Roza, Hesselstrand, Roger, Wollheim, Frank, Wuttge, Dirk M, Andreasson, Kristofer, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Trotta, Francesco, Lo Monaco, Andrea, Hunzelmann, Nicolas, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Morovic-Vergles, Jadranka, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthias, Hasler, Paul, Burkhardt, Harald, Himsel, Andrea, Bajocchi, Gianluigi, Nuova, Arcispedale Santa Maria, Salvador, Maria Joao, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Marasini, Bianca, Tikly, Mohammed, Ananieva, Lidia P, Denisov, Lev N, Mueller-Ladner, Ulf, Frerix, Marc, Tarner, Ingo, Scorza, Raffaella, Puppo, Francesco, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szucs, Gabriella, Szamosi, Szilvia, Zea Mendoza, Antonio, de la Puente, Carlos, Sifuentes Giraldo, Walter Alberto, Midtvedt, Oyvind, Reiseter, Silje, Garen, Torhild, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Soare, Alina, Gorga, Marilena, Bojinca, Mihai, Mihai, Carina, Milicescu, Mihaela, Sunderkoetter, Cord, Kuhn, Annegret, Sandorfi, Nora, Schett, Georg, Distler, Joerg HW, Beyer, Christian, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, von Muehlen, Carlos Alberto, Bohn, Jussara Marilu, Lonzetti, Lilian Scussel, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Houssiau, Frederic A, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Westhovens, Rene, de Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Jimenez, Sergio, Busquets, Joanna, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Popa, Sergei, Zenone, Thierry, Pileckyte, Margarita, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D, Yoshinari, Natalino H, Marangoni, Roberta G, Martin, Patricia, Fuocco, Luiza, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Mohamed, Walid Ahmed Abdel Atty, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Chirieac, Rodica, Ancuta, Codrina, Furst, Daniel E, Villiger, Peter, Adler, Sabine, van Laar, Jacob, Kayser, Cristiane, Eduardo, Andrade Luis C, Fathi, Nihal, Hassanien, Manal, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Emery, Paul, Buch, Maya, Del Galdo, Francesco, Venalis, Algirdas, Butrimiene, Irena, Venalis, Paulius, Rugiene, Rita, Karpec, Diana, Saketkoo, Lesley Ann, Lasky, Joseph A, Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Rosner, Itzhak, Rozenbaum, Michael, Slobodin, Gleb, Boulman, Nina, Rimar, Doron, Couto, Maura, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Kahl, Sarah, Hsu, Vivien M, Chen, Fei, McCloskey, Deborah, Malveaux, Halina, Pasquali, Jean Louis, Martin, Thierry, Gorse, Audrey, Guffroy, Aurelien, Poindron, Vincent, EUSTAR Collaborators, Guiducci, S., Walker, U., Kyburz, D., Lapadula, G., Iannone, F., Maurer, B., Jordan, S., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Siegert, E., Rednic, S., Nicoara, I., Kahan, A., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Stork, J., Inanc, M., Carreira, P.E., Novak, S., Czirják, L., Varju, C., Chizzolini, C., Kucharz, E.J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Wu, C., Marjanovic, Z., Faivre, H., Hij, D., Dhamadi, R., Airò, P., Hesselstrand, R., Wollheim, F., Wuttge, D.M., Andréasson, K., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Trotta, F., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Mauriziano, O., Maria Bambara, L., Caramaschi, P., Morovic-Vergles, J., Black, C., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Burkhardt, H., Himsel, A., Bajocchi, G., Maria Nuova, A.S., João Salvador, M., Pereira Da Silva, J.A., Stamenkovic, B., Stankovic, A., Francesco Selmi, C., De Santis, M., Marasini, B., Tikly, M., Ananieva, L.P., Denisov, L.N., Müller-Ladner, U., Frerix, M., Tarner, I., Scorza, R., Puppo, F., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szücs, G., Szamosi, S., Zea Mendoza, A., de la Puente, C., Sifuentes Giraldo, W.A., Midtvedt, Ø., Reiseter, S., Garen, T., Valesini, G., Riccieri, V., Maria Ionescu, R., Opris, D., Groseanu, L., Wigley, F.M., Sfrent Cornateanu, R., Ionitescu, R., Maria Gherghe, A., Soare, A., Gorga, M., Bojinca, M., Mihai, C., Milicescu, M., Sunderkötter, C., Kuhn, A., Sandorfi, N., Schett, G., Distler, J.H., Beyer, C., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Paolo Cantatore, F., Corrado, A., Ullman, S., Iversen, L., Alberto von Mühlen, C., Marilu Bohn, J., Scussel Lonzetti, L., Rosa Pozzi, M., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Houssiau, F.A., Jose Alegre-Sancho, J., Krummel-Lorenz, B., Saar, P., Aringer, M., Günther, C., Westhovens, R., de Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Üprus, M., Otsa, K., Yavuz, S., Granel, B., Cezar Radominski, S., de Souza Müller, C., Azevedo, V.F., Jimenez, S., Busquets, J., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Popa, S., Zenone, T., Pileckyte, M., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Sampaio-Barros, P.D., Yoshinari, N.H., Marangoni, R.G., Martin, P., Fuocco, L., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Abdel Atty Mohamed, W.A., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C.M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Chirieac, R., Ancuta, C., Furst, D.E., Villiger, P., Adler, S., van Laar, J., Kayser, C., Eduardo C, A.L., Fathi, N., Hassanien, M., de la Peña Lefebvre, P.G., Rodriguez Rubio, S., Valero Exposito, M., Sibilia, J., Chatelus, E., Gottenberg, J.E., Chifflot, H., Litinsky, I., Emery, P., Buch, M., Del Galdo, F., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Ann Saketkoo, L., Lasky, J.A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Luca Brucato, A., Lupi, E., Rosner, I., Rozenbaum, M., Slobodin, G., Boulman, N., Rimar, D., Couto, M., Spertini, F., Ribi, C., Buss, G., Kahl, S., Hsu, V.M., Chen, F., McCloskey, D., Malveaux, H., Louis Pasquali, J., Martin, T., Gorse, A., Guffroy, A., Poindron, V., and Chizzolini, Carlo
Subjects: 0301 basic medicine, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Databases, Factual, systemic sclerosis, SUBSETS, Disease, Severity of Illness Index, Scleroderma, DISEASE, 0302 clinical medicine, Medicine and Health Sciences, Immunology and Allergy, Cluster Analysis, CRITERIA, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, integumentary system, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Adult, Aged, Autoantibodies/blood, Europe/epidemiology, Female, Humans, Middle Aged, Phenotype, Prognosis, Scleroderma, Diffuse/blood, Scleroderma, Diffuse/epidemiology, Scleroderma, Diffuse/pathology, Scleroderma, Limited/blood, Scleroderma, Limited/epidemiology, Scleroderma, Limited/pathology, Scleroderma, Systemic/blood, Scleroderma, Systemic/epidemiology, Scleroderma, Systemic/pathology, Connective tissue disease, ddc, Europe, MANIFESTATIONS, Cohort, Life Sciences & Biomedicine, medicine.medical_specialty, Immunology, PROFILE, CLASSIFICATION, 03 medical and health sciences, Rheumatology, Scleroderma, Limited, Internal medicine, Severity of illness, medicine, Autoantibodies, 030203 arthritis & rheumatology, Science & Technology, Scleroderma, Systemic, business.industry, Autoantibody, Systemic sclerosis (SSc), medicine.disease, 030104 developmental biology, Scleroderma, Diffuse, business
Abstract: OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. METHODS: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. RESULTS: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. CONCLUSION: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis. ispartof: ARTHRITIS & RHEUMATOLOGY vol:71 issue:9 pages:1553-1570 ispartof: location:United States status: published
Published: 2019

11. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth A Systematic Review and Meta-analysis

Author: Wichor M. Bramer, Leda Chatzi, Polina V. Popova, Lorena Mosso, Margreet Meems, Layal Chaker, Arash Derakhshan, Jordi Sunyer, Eric A. P. Steegers, Colin M. Dayan, Peter N. Taylor, Tuija Männistö, Suzanne J. Brown, Elena N. Grineva, Isolina Riaño, Ulla Feldt-Rasmussen, Judit Bassols, Emily Oken, Victor J M Pop, Jun Yoshinaga, Mònica Guxens, Juha Auvinen, Alexandra S. Tkachuck, Scott M. Nelson, Bijay Vaidya, Tanja G. M. Vrijkotte, Shafqat Mukhtar, Xuemian Lu, Christian Delles, Mario Murcia, David M. Carty, Farkhanda Ghafoor, Liangmiao Chen, Tim I M Korevaar, Elizabeth N. Pearce, Sofie Bliddal, Abel López-Bermejo, Ana Jiménez-Zabala, Laura Boucai, John P. Walsh, Beverley M. Shields, Marcel E Meima, Robin P. Peeters, Aya Hisada, Erik K. Alexander, Eila Suvanto, Marina Vafeiadi, Internal Medicine, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, Obstetrics & Gynecology, Public and occupational health, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, Amsterdam Reproduction & Development (AR&D), APH - Methodology, Medical and Clinical Psychology, Epidemiology, and Applied Economics
Subjects: Thyrotropin/blood, Iodide Peroxidase/immunology, Premature Birth/etiology, Thyrotropin, Hypothyroidism/complications, Thyroid Function Tests, 01 natural sciences, Thyroxine/blood, 0302 clinical medicine, Maternal hypothyroidism, Thyroid Diseases/blood, Pregnancy, Euthyroid, 030212 general & internal medicine, 030219 obstetrics & reproductive medicine, biology, medicine.diagnostic_test, Obstetrics, Thyroid disease, Absolute risk reduction, Obstetrics and Gynecology, Gestational age, General Medicine, Premature birth, Premature Birth, Female, Thyroid function, medicine.drug, Adult, endocrine system, medicine.medical_specialty, Levothyroxine, Gestational Age, Iodide Peroxidase, Thyroid function tests, Autoimmune Diseases, 03 medical and health sciences, Hypothyroidism, Thyroid peroxidase, medicine, Very Preterm Birth, Humans, 0101 mathematics, Autoantibodies, business.industry, 010102 general mathematics, Infant, Newborn, Infant, Odds ratio, Newborn, medicine.disease, Thyroid Diseases, Pregnancy Complications/blood, Pregnancy Complications, Thyroxine, Autoimmune Diseases/blood, biology.protein, Autoantibodies/blood, business
Abstract: Preterm birth complicates 5% to 15% of births worldwide, and although it is the most important direct cause of morbidity and mortality in children younger than 5 years, no known risk factors can be identified in the majority of cases. However, overt hypothyroidism and hyperthyroidism during pregnancy are well-known risk factors for preterm birth, and as such, the purpose of this study was to assess whether thyroid function test abnormalities and thyroid peroxidase (TPO) antibody positivity were associated with preterm birth. The study conducted a systematic review on the association of thyroid function or autoimmunity with preterm birth published from database inception to March 18, 2018, without language restrictions, using the Ovid MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Possible studies for inclusion were independently assessed for suitability by 2 of the authors, and study quality and risk of bias were assessed using the Newcastle-Ottawa Scale. Then, authors were contacted to ascertain interest in participating in the individual patient meta-analysis. The primary outcome was preterm birth defined as a gestational age at birth of less than 37 weeks, as assessed using either ultrasound measurements or time after the last menstrual period. Secondary outcomes were very preterm birth (
Published: 2019

12. Diabetes mellitus induced by PD-1 and PD-L1 inhibitors: description of pancreatic endocrine and exocrine phenotype

Author: Charles Thivolet, Karim Chikh, Lucien Marchand, Nicole Fabien, Sophie Reffet, Julien Vouillarmet, Christine Cugnet-Anceau, Arnaud Thivolet, Stéphane Dalle, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Immune checkpoint inhibitors side-effects, Male, Durvalumab, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, Mixed meal test, Pembrolizumab, 030204 cardiovascular system & hematology, Anti-PD-L1, Gastroenterology, B7-H1 Antigen, B7-H1 Antigen/antagonists & inhibitors/*immunology, Autoimmune diabetes, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Monoclonal, 80 and over, Fulminant diabetes, Programmed death ligand 1, Aged, 80 and over, Antibodies, Monoclonal, General Medicine, Middle Aged, Programmed Cell Death 1 Receptor/antagonists & inhibitors/*immunology, Pancreas, Exocrine, Alpha-cell pancreatic function, Anti-PD-1, 3. Good health, Nivolumab, Editorial, medicine.anatomical_structure, Phenotype, Female, Immunotherapy, Pancreas, Monoclonal/adverse effects, medicine.medical_specialty, Exocrine/*drug effects/metabolism/pathology, 030209 endocrinology & metabolism, Beta-cell pancreatic function, Antibodies, Monoclonal, Humanized, Antibodies, Islets of Langerhans/*drug effects/metabolism/pathology, Islets of Langerhans, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, Endocrine system, Humans, Immunotherapy/*adverse effects, Autoantibodies, Aged, Type 1 diabetes, business.industry, Pancreas volume, Programmed cell death-1, medicine.disease, Nivolumab/adverse effects, Diabetes Mellitus/*chemically induced/pathology, Ketoacidosis, Exocrine pancreatic function, Humanized/adverse effects, business, Autoantibodies/blood
Abstract: AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FD patient was not found in other FD subjects, but glucagon response was blunted in another FD patient. Pancreas volume was decreased at diabetes onset in 2 FD patients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.
Published: 2019

13. Biological and Clinical Response to Omalizumab in a Patient with Bullous Pemphigoid

Author: Lionel Fontao, Guerkan Kaya, Emmanuel Laffitte, Sébastien Menzinger, and Enno Schmidt
Subjects: 0301 basic medicine, medicine.medical_specialty, Skin/drug effects/immunology/pathology, Dystonin, Biopsy, Omalizumab/therapeutic use, Immunoglobulin E/blood, Fluorescent Antibody Technique, Omalizumab, Dermatology, Autoantigens, Severity of Illness Index, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Autoantigens/immunology, Pemphigoid, Bullous, medicine, lcsh:Dermatology, Immunologic Factors, Humans, Autoantibodies, Skin, Aged, ddc:616, business.industry, Remission Induction, General Medicine, Immunoglobulin E, Non-Fibrillar Collagens, lcsh:RL1-803, medicine.disease, Immunologic Factors/therapeutic use, Dystonin/immunology, Treatment Outcome, 030104 developmental biology, Bullous/blood/diagnosis/drug therapy/immunology, Female, Bullous pemphigoid, Autoantibodies/blood, business, Pemphigoid, Biomarkers, Biomarkers/blood, Non-Fibrillar Collagens/immunology, medicine.drug
Published: 2017

14. Association between anti-apolipoprotein A-1 antibodies and cardiovascular disease in the general population

Author: Nathalie Satta, Peter Vollenweider, Julien Virzi, Nicolas Vuilleumier, Oliver Hartley, François Bastardot, Fabrizio Montecucco, Panagiotis Antiochos, François Mach, Gérard Waeber, Sabrina Pagano, and Pedro Marques-Vidal
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Apolipoprotein B, Cross-sectional study, Anti-apolipoprotein A-1 antibodies, Population, Apolipoprotein A-I/immunology, Autoantibodies/blood, Cardiovascular Diseases/blood, Cardiovascular Diseases/immunology, Cross-Sectional Studies, Female, Humans, Immunoglobulin G/blood, Middle Aged, biomarker, cardiovascular disease, high-density lipoprotein cholesterol, population-based, ddc:616.07, 030204 cardiovascular system & hematology, Gastroenterology, Angina, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Myocardial infarction, education, Stroke, Autoantibodies, education.field_of_study, Apolipoprotein A-I, biology, business.industry, Hematology, Odds ratio, medicine.disease, 3. Good health, 030104 developmental biology, Cardiovascular Diseases, Immunoglobulin G, Immunology, biology.protein, lipids (amino acids, peptides, and proteins), business
Abstract: SummaryWe aimed to determine the association between autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) and prevalent cardiovascular (CV) disease (CVD) as well as markers of CV risk in the general population. Cross-sectional data were obtained from 6649 subjects (age 52.6 ± 10.7 years, 47.4 % male) of the population-based CoLaus study. CVD was defined as myocardial infarction, angina pectoris, percutaneous revascularisation or bypass grafting for ischaemic heart disease stroke or transient ischaemic attack, and was assessed according to standardised medical records. Anti-apoA-1 IgG and biological markers were measured by ELISA and conventional automated techniques, respectively. Prevalence of high anti-apoA-1 IgG levels in the general population was 19.9 %. Presence of anti-apoA-1 IgG was significantly associated with CVD [odds ratio 1.34, 95 % confidence interval (1.05–1.70), p=0.018], independently of established CV risk factors (CVRFs) including age, sex, hypertension, smoking, diabetes, low and high-density lipoprotein cholesterol levels. The n=455 (6.8 %) study participants with a history of CVD (secondary prevention subgroup) presented higher median anti-ApoA-1 IgG values compared with subjects without CVD (p=0.029). Among patients in the secondary prevention subgroup, those with positive anti-apoA-1 IgG levels had lower HDL (p=0.002) and magnesium (p=0.001) levels, but increased uric acid and high-sensitivity C-reactive protein levels (p=0.022, and p
Published: 2016

15. Effects of rituximab and dexamethasone on regulatory and proinflammatory B-cell subsets in patients with primary immune thrombocytopenia

Author: Gudbrandsdottir, Sif, Brimnes, Marie, Køllgaard, Tania, Hasselbalch, Hans C, Nielsen, Claus H, Gudbrandsdottir, Sif, Brimnes, Marie, Køllgaard, Tania, Hasselbalch, Hans C, and Nielsen, Claus H
Abstract: OBJECTIVE: To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM).METHODS: Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell-surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL-6 and IL-10 were measured by flow cytometry.RESULTS: PBMCs from ITP patients at baseline contained a lower proportion of IL-10+ B cells (P < .01) and IL-6+ B cells (P < .01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5+ B cells increased (P < .01) and CD27+ memory B cells decreased (P < .05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27+ B cells (R = -0.71; P < .05).CONCLUSION: Both treatment regimens normalized the frequencies of cytokine-producing B cells. The additional increase in CD5+ B cells after RTX+DXM is compatible with induction of Bregs.
Published: 2018

16. Clinical utility of anti-MOG antibody testing in a Danish cohort

Author: Papp, Viktoria, Langkilde, Annika R, Blinkenberg, Morten, Schreiber, Karen, Jensen, Poul Erik Hyldgaard, Sellebjerg, Finn, Papp, Viktoria, Langkilde, Annika R, Blinkenberg, Morten, Schreiber, Karen, Jensen, Poul Erik Hyldgaard, and Sellebjerg, Finn
Abstract: BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be found in different immune-mediated inflammatory CNS disorders. The full range of clinical manifestations may not have been fully discovered yet.METHODS: In a cross-sectional study 184 adults (age ≥ 16) were tested for anti-MOG antibody (Ab) with a cell-based assay. To define the relevant target population for anti-MOG antibody testing in a neurology clinic, we divided the entire study population based on the presenting symptoms and classified cases followed for multiple sclerosis (MS) according to the clinical features and response to disease-modifying therapy.RESULTS: We identified eight (4.4%) MOG-Ab positive cases in the whole cohort. All eight cases had first manifestations suggestive of neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease courses and responses to therapy. This included a patient with chronic relapsing inflammatory optic neuropathy (CRION) responding only to therapy with infliximab. Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab showed atypical features and had poor response to therapy.CONCLUSION: A broad range of clinical and radiological features of anti-MOG associated disorder was observed in a single centre. MOG-Ab testing should be considered in patients with an NMOSD phenotype and in MS patients presenting atypical features. The potential use of infliximab therapy for MOG-Ab disease should be further investigated.
Published: 2018

17. Onset of connective tissue disease following anti-PD1/PD-L1 cancer immunotherapy

Author: Pascale Chrétien, Xavier Mariette, Jean-Marie Michot, Sébastien Le Burel, Laurence Albiges, Anne-Laure Voisin, Stéphane Champiat, Emilie Routier, Sandrine Aspeslagh, Olivier Lambotte, Tali-Anne Szwebel, Medical Oncology, and Laboratory for Medical and Molecular Oncology
Subjects: Antineoplastic Agents, Immunological/adverse effects, Male, medicine.medical_specialty, Immunology, Autoimmunity, General Biochemistry, Genetics and Molecular Biology, Connective Tissue Diseases/chemically induced, Autoimmune Diseases, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Rheumatology, Neoplasms, medicine, Humans, Immunology and Allergy, Sjøgren's Syndrome, Prospective Studies, Registries, Connective Tissue Diseases, Adverse effect, Prospective cohort study, Cryoglobulinemic vasculitis, Myositis, Aged, Autoantibodies, 030203 arthritis & rheumatology, Biochemistry, Genetics and Molecular Biology(all), business.industry, Autoantibody, Cancer, Middle Aged, medicine.disease, Connective tissue disease, Dermatology, Neoplasms/drug therapy, Treatment, 030220 oncology & carcinogenesis, Female, Autoantibodies/blood, business, Complication
Abstract: Although treatment with immune checkpoint inhibitors (ICIs) is associated with better survival in many cancer settings, these therapeutics can induce immune-related adverse events (IrAEs).1 ,2 REISAMICi is a French, prospective, multicentre, academic registry sponsored by the Gustave Roussy Institute cancer centre. The objective is to better detect, document and manage IrAEs. Connective tissue diseases (CTD) have not previously been reported in patients treated with anti-PD1/PDL-1 agents. The REISAMIC registry was screened for reports of CTD. Of the 447 patients supervised in the REISAMIC registry, three have developed CTD: two cases of Sjogren's syndrome and one case of cryoglobulinemic vasculitis as a complication of suspected Sjogren's syndrome (table 1). A case of ANA+ myositis registered in REISAMIC by another investigating centre …
Published: 2017

18. Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus

Author: Carlo Chizzolini, Denise Dubler, Lucia Schirmbeck, Justa Friebus-Kardash, Uyen Huynh-Do, Camillo Ribi, Josephine Nehring, and Marten Trendelenburg
Subjects: 0301 basic medicine, Male, Medizin, Adolescent, Adult, Aged, Aged, 80 and over, Autoantibodies/blood, Autoantibodies/immunology, Cohort Studies, Female, Humans, Immunoglobulin G/blood, Immunoglobulin G/immunology, Lupus Erythematosus, Systemic/blood, Lupus Erythematosus, Systemic/immunology, Middle Aged, Serum Albumin, Human/immunology, Serum Albumin, Human/metabolism, antibodies, human serum albumin, multicenter study, patients, systemic lupus erythematosus, 0302 clinical medicine, Immunology and Allergy, Medicine, Lupus Erythematosus, Systemic, Bovine serum albumin, skin and connective tissue diseases, Original Research, ddc:616, biology, Human serum albumin, 3. Good health, 030220 oncology & carcinogenesis, embryonic structures, Antibody, medicine.drug, lcsh:Immunologic diseases. Allergy, Immunology, Serum albumin, 610 Medicine & health, Serum Albumin, Human, 03 medical and health sciences, Immune system, Autoantibodies, business.industry, Albumin, Autoantibody, Fast protein liquid chromatography, body regions, 030104 developmental biology, Immunoglobulin G, biology.protein, business, lcsh:RC581-607
Abstract: Objectives: Autoantibodies and aberrant immune complexes are pathological hallmarks of systemic lupus erythematosus (SLE). This study aimed to determine the occurrence of IgG autoantibodies against human serum albumin (anti-HSA IgG) and their potential association with antibodies against bovine serum albumin (anti-BSA IgG) in patients with SLE. Methods: Sera of 180 SLE patients included to the Swiss SLE Cohort Study and 188 age- and sex-matched healthy controls were evaluated. Levels of anti-HSA IgG and anti-BSA IgG were quantified by ELISA. Selected samples were further characterized using serum fractions obtained by fast liquid chromatography (FPLC). Results: SLE patients had increased levels of anti-HSA IgG (p = 0.002) but similar levels of anti-BSA IgG compared to matched healthy controls. Anti-HSA IgG levels correlated with the SLE Disease Activity Index (SLEDAI), which was more pronounced in patients with an physician's global assessment (PGA) of ≥ 1 (r = 0.309, p = 0.0066). Anti-HSA IgG was partially complexed with serum albumin but also occurred as monomeric autoantibodies in highly positive SLE patients. A positive correlation between anti-HSA IgG and anti-BSA IgG was found that was stronger in SLE patients than in healthy controls (r = 0.3172, p < 0.001 vs. r = 0.2122, p < 0.0035). Binding of anti-BSA IgG was inhibited partially in the presence of HSA in samples with double positivity for anti-HSA and anti-BSA (median inhibition 47.9%, range 0.9–100%) and vice versa. Conclusion: In SLE patients there is an increased prevalence of anti-HSA IgG antibodies that are associated with SLE disease activity. CA extern
Published: 2018

19. Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies

Author: Roger Walz, Fabricio Souza Neves, Peter Wolf, Katia Lin, Mário Steindel, Christian Pereira Gregory, Adaucto W. Nóbrega-Jr, and Rachel Schlindwein-Zanini
Subjects: 0301 basic medicine, Male, Adult, Pathology, medicine.medical_specialty, Adolescent, autoantibodies, Nerve Tissue Proteins, Receptors, Ionotropic Glutamate, Hippocampus, Sclerosis/blood, 03 medical and health sciences, Epilepsy, Receptors, Ionotropic Glutamate/immunology, Young Adult, 0302 clinical medicine, Glioma, Hippocampus/pathology, Membrane Proteins/immunology, Medicine, Humans, Autoantibodies, Aged, Autoimmune encephalitis, Hippocampal sclerosis, Sclerosis, business.industry, Glutamate Decarboxylase, Limbic encephalitis, Autoantibody, Membrane Proteins, temporal lobe epilepsy, Middle Aged, medicine.disease, 030104 developmental biology, Nerve Tissue Proteins/immunology, Neurology, Epilepsy, Temporal Lobe, hippocampal sclerosis, Case-Control Studies, Glutamate Decarboxylase/immunology, Etiology, Epilepsy, Temporal Lobe/blood, Female, Neurology (clinical), business, Autoantibodies/blood, 030217 neurology & neurosurgery, Encephalitis
Abstract: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is characterized by its well-defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult-onset MTLE-HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE-HS. A case-control study was carried out with 100 patients with MTLE-HS and 50 healthy controls. Sera samples from subjects were tested by indirect immunofluorescence assay for detection of anti-N-methyl-d-aspartate receptor (NMDA-R), anti-contactin-associated protein-like 2 (CASPR2), anti-leucine-rich glioma inactivated 1 (LGI1), anti-gamma aminobutyric acid B receptor (GABA-B-R), anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2 receptors (AMPA-1-R and AMPA-2-R), and enzyme-linked immunosorbent assay for detection of anti-glutamic acid decarboxylase 65 (GAD65). Mean age of patients and controls was 41.2 vs 42 years, and 55% vs 56% were female. Mean duration of epilepsy was 27.2 years. No neuronal autoantibodies were found in either group, except for anti-GAD65 in 3 patients and 2 controls. This study adds to the mounting evidence that, in Brazilian patients, MTLE-HS without signs and symptoms of autoimmune encephalitis may be infrequently associated with these autoantibodies. Differences regarding accuracy of used methodologies for autoantibody detection and genetic and environmental characteristics are discussed. Further works with different methodologies tested simultaneously in different populations may help clarify the incongruent study results about autoantibodies in MTLE-HS.
Published: 2018

20. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

Author: Jarius, S, Paul, F, Aktas, O, Asgari, N, Dale, RC, De Seze, J, Franciotta, D, Fujihara, K, Jacob, A, Kim, HJ, Kleiter, I, Kümpfel, T, Levy, M, Palace, J, Ruprecht, K, Saiz, A, Trebst, C, Weinshenker, BG, Wildemann, B, and Universitat de Barcelona
Subjects: Optic Neuritis, Internationality, Esclerosi múltiple, Review, Optic neuritis (ON), Myelitis, lcsh:RC346-429, Multiple sclerosis, Immunoenzyme Techniques, 610 Medical sciences Medicine, Diagnòstic, immune system diseases, Myelin oligodendrocyte glycoprotein (MOG) antibodies, Diagnosis, Mielitis, Animals, Humans, Consensus recommendations, Encephalomyelitis, Expert Testimony, Neuromyelitis optica spectrum disorders (NMOSD), lcsh:Neurology. Diseases of the nervous system, Autoantibodies, Aquaporin 4, Myelin-Oligodendrocyte Glycoprotein/blood, Malalties del sistema nerviós central, Neuromyelitis Optica, Immunoenzyme Techniques/methods, Antibody testing, Myelitis, Multiple sclerosis (MS), nervous system diseases, nervous system, Immunoglobulin G/blood, Immunoglobulin G, Myelin-Oligodendrocyte Glycoprotein, Function and Dysfunction of the Nervous System, Autoantibodies/blood, Encephalomyelitis/blood, Biomarkers/blood, Central nervous system diseases, Biomarkers
Abstract: Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.
Published: 2018

21. Predictive score for the development or progression of Graves’ orbitopathy in patients with newly diagnosed Graves’ hyperthyroidism

Author: Eugogo, Georg von Arx, Simone Donati, Mario Salvi, Laszlo Hegedüs, Petros Perros, Daniel J. Morris, Chantal Daumerie, Wilmar M. Wiersinga, Maria-Christina Burlacu, Onyebuchi E. Okosieme, Danila Covelli, Fusun Balos Toruner, Jürg Lareida, Nicola Currò, Thomas Heiberg Brix, Jasmina Ciric, Nicole Fichter, Göksun Ayvaz, George J. Kahaly, Onur Konuk, Luigi Bartalena, Miloš Žarković, Biljana Beleslin, Susanne Pitz, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, and Academic Medical Center
Subjects: Male, Time Factors, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Thyrotropin, Logistic regression, Graves Disease/diagnosis, 0302 clinical medicine, Endocrinology, Thyrotropin/immunology, Positive predicative value, Odds Ratio, Prospective Studies, Prospective cohort study, Smoking, General Medicine, Middle Aged, Prognosis, Graves Disease, 3. Good health, Europe, Diabetes and Metabolism, Female, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, endocrine system, Graves hyperthyroidism, 030209 endocrinology & metabolism, Newly diagnosed, Europe/epidemiology, 03 medical and health sciences, Antithyroid Agents, Internal medicine, medicine, Humans, In patient, Autoantibodies, business.industry, Odds ratio, Antithyroid Agents/therapeutic use, eye diseases, Graves Ophthalmopathy, Graves Ophthalmopathy/diagnosis, Logistic Models, 030221 ophthalmology & optometry, Observational study, Autoantibodies/blood, business
Abstract: Objective To construct a predictive score for the development or progression of Graves’ orbitopathy (GO) in Graves’ hyperthyroidism (GH). Design Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. Methods 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. Results GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6–12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2–10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1–4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20–0.37) and 0.91 (95% CI 0.87–0.94) respectively. Conclusions In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.
Published: 2018

22. Juvenile autoimmune hepatitis: A comprehensive review

Author: Christiane Sokollik, Giorgina Mieli-Vergani, Diego Vergani, Valérie A. McLin, and Benedetta Terziroli Beretta-Piccoli
Subjects: Liver Failure/diagnosis/immunology/pathology/therapy, Cholangitis, medicine.medical_treatment, Azathioprine, Autoimmune hepatitis, Liver transplantation, Immunoglobulin G, Hepatitis, Liver disease, 0302 clinical medicine, Recurrence, Transaminases/blood, Immunology and Allergy, Autoimmune/diagnosis/immunology/pathology/therapy, Child, 610 Medicine & health, Sclerosing/diagnosis/immunology/pathology/therapy, Pediatric, ddc:618, biology, Disease Management, Hepatitis, Autoimmune, Steroids, 030211 gastroenterology & hepatology, medicine.symptom, Immunosuppressive Agents, medicine.drug, Adult, Adolescent, Cholangitis, Sclerosing, Immunology, Asymptomatic, Steroids/therapeutic use, 03 medical and health sciences, Anti-smooth muscle antibody, 030225 pediatrics, medicine, Humans, Juvenile autoimmune hepatitis, Anti-liver kidney microsomal type 1 antibody, Interface hepatitis, Transaminases, Autoantibodies, business.industry, Autoantibody, medicine.disease, Liver Transplantation, Immunoglobulin G/blood, biology.protein, Immunosuppressive Agents/therapeutic use, business, Autoantibodies/blood, Azathioprine/therapeutic use, Liver Failure, Acute liver failure
Abstract: Autoimmune hepatitis (AIH) is a rare, chronic disease that affects both adults and children, including infants. The disease is probably triggered by environmental factors in genetically predisposed individuals. The clinical presentation ranges from asymptomatic patients or patients with non-specific symptoms, such as fatigue, to fulminant liver failure, many children presenting with symptoms indistinguishable from those of acute hepatitis. Raised transaminase and immunoglobulin G (IgG) levels, in association with circulating autoantibodies, guide towards the diagnosis. The histological hallmark is interface hepatitis, which however is non-specific and may be absent. There are no bile duct changes on cholangiography. Presence of anti-nuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA) is characteristic for type 1 AIH, whereas presence of anti-liver kidney microsomal type 1 (LKM1) antibody and/or anti-liver cytosol type 1 (LC1) antibody defines type 2 AIH. The latter accounts for about one third of the juvenile AIH cases, presents more acutely than type 1 AIH and is very rare in adults. Immunosuppressive therapy, based on steroids and azathioprine, is required, and in the vast majority of patients leads to clinical and biochemical remission, defined as absence of symptoms, normal transaminase and IgG levels, and negative or low-titer autoantibodies. In patients intolerant or non-responder to standard therapy, a number of second line drugs have been employed with variable results. For the rare cases who progress to end-stage liver disease, liver transplantation is life-saving, but recurrence of the disease is possible. A better understanding of the underlying pathogenic mechanisms will help to develop new, more effective and less toxic therapies, and to tailor treatment regimens to the individual patient.
Published: 2018
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23. Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies:a national cohort study

Author: Celicanin, M, Blaabjerg, M, Maersk-Moller, C, Beniczky, S, Marner, L, Thomsen, C, Bach, F W, Kondziella, D, Andersen, H, Somnier, F, Illes, Z, Pinborg, L H, Celicanin, M, Blaabjerg, M, Maersk-Moller, C, Beniczky, S, Marner, L, Thomsen, C, Bach, F W, Kondziella, D, Andersen, H, Somnier, F, Illes, Z, and Pinborg, L H
Abstract: BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016.METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field.RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year.CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awarene
Published: 2017

24. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN):a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Author: Howard, James F, Utsugisawa, Kimiaki, Benatar, Michael, Murai, Hiroyuki, Barohn, Richard J, Illa, Isabel, Jacob, Saiju, Vissing, John, Burns, Ted M, Kissel, John T, Muppidi, Srikanth, Nowak, Richard J, O'Brien, Fanny, Wang, Jing-Jing, Mantegazza, Renato, Howard, James F, Utsugisawa, Kimiaki, Benatar, Michael, Murai, Hiroyuki, Barohn, Richard J, Illa, Isabel, Jacob, Saiju, Vissing, John, Burns, Ted M, Kissel, John T, Muppidi, Srikanth, Nowak, Richard J, O'Brien, Fanny, Wang, Jing-Jing, and Mantegazza, Renato
Abstract: BACKGROUND: Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial.METHODS: We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discret
Published: 2017

25. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice

Author: Sven Seiwerth, Annette M. Müller, Manfred Ratschek, Bożena Cukrowska, Gemma Castillejo, Vanesa Morente, Jorge Amil Dias, Sara Morgenstern, Marco Gasparetto, Nailah Brown, Alexandra Papadopoulou, Gabriele Amann, Kalle Kurppa, Vincenzo Villanacci, Almuthe C. Hauer, Francesc Martínez, Miguel Bolonio, Anikó Nagy, Tine Plato Hansen, Yvan Vandenplas, Sonja Thanner-Lechner, Kaija Laurila, Rita Kőbányai, Søren Thue Lillevang, Zrinjka Mišak, Riccardo Troncone, Pavel Frűhauf, Adina Ene, Jernej Dolinsek, Konstantina Dimakou, Fabio Massimo Magliocca, Annieta Goossens, Vered Nachmias Friedler, Maryam Monajemzadeh, Amir Taher Eftekhar Sadat, Mandana Rafeey, Jan Wyhowski, Rafaella Nenna, Françoise Smets, Hélène Garnier-Lengliné, Marianna Salemme, Martine Vornane, Stine Dydensborg Sander, Hany Banoub, Anne Mourin, Mariantonia Maglio, Stephanie Van Biervliet, Birgit Filipiak, M. L. Mearin, Mehri Najafi, Gauri Batra, Judit Gyimesi, Hubert Kogler, Gabriele Heilig, Raanan Shamir, Laura Petrarca, Katayoun Khatami, Myriam Van Winckel, Susana Corujeira, Hania Szajewska, Ilma Rita Korponay-Szabó, Alina Popp, Stefan Buderus, Sonny K. F. Chong, Elke Janssens, Francesca Penagini, Vincent T.H.B.M. Smit, Judit B. Kovács, Rajko Kavalar, Thomas Kirchner, Carmen Ribes-Koninckx, Renata Auricchio, Ruth Achten, Ester Donat, Catherine Wanty, Nicolas Kalach, Danielle Canioni, Philippe Alliet, Ilona Lellei, Sibylle Koletzko, Yulia Dmitrieva, Fátima Carneiro, Liz Hook, David Fernández Ramos, Roberta Kosova, Dmitry Abramov, Markku Mäki, Helena Skalova, Adrian G. Thomas, Steffen Husby, Steve Sampson, Katharina Julia Werkstetter, Piotr Socha, Andreas Vécsei, Amalia Patereli, Peter Szitanyi, Saskia Vande Velde, Maaike W. Schaart, Pierre Gosset, Growth and Development, Clinical sciences, Werkstetter, K. J, Korponay Szabó, I. R, Popp, A, Villanacci, V, Salemme, M, Heilig, G, Lillevang, S. T, Mearin, M. L, Ribes Koninckx, C, Thomas, A, Troncone, Riccardo, Filipiak, B, Mäki, M, Gyimesi, J, Najafi, M, Dolinšek, J, Dydensborg Sander, S, Auricchio, Renata, Papadopoulou, A, Vécsei, A, Szitanyi, P, Donat, E, Nenna, R, Alliet, Ph, Penagini, F, Garnier Lengliné, H, Castillejo, G, Kurppa, K, Shamir, R, Hauer, A. C, Smets, F, Corujeira, S, van Winckel, M, Buderus, S, Chong, S, Husby, S, Koletzko, S, Socha, Piotr, Bozena Cukrowska, Null, Szajewska, Hania, Wyhowski, Jan, Brown, Nailah, Batra, Gauri, Misak, Zrinjka, Seiwerth, Sven, Dmitrieva, Yulia, Abramov, Dmitry, Vandenplas, Yvan, Goossens, Annieta, Schaart, Maaike W, Smit, V. T. H. B. M, Kalach, Nicola, Gosset, Pierre, Kovács, Judit B, Nagy, Anikó, Lellei, Ilona, Kőbányai, Rita, Khatami, Katayoun, Monajemzadeh, Maryam, Dimakou, Konstantina, Patereli, Amalia, Plato Hansen, Tine, Kavalar, Rajko, Bolonio, Miguel, Kogler, Hubert, Amann, Gabriele, Kosova, Roberta, Maglio, Mariantonia, Janssens, Elke, Achten, Ruth, Frűhauf, Pavel, Skálová, Helena, Kirchner, Thoma, Petrarca, Laura, Magliocca, Fabio Massimo, Martínez, Francesc, Morente, Vanesa, Thanner Lechner, Sonja, Ratschek, Manfred, Gasparetto, Marco, Hook, Liz, Canioni, Danielle, Wanty, Catherine, Mourin, Anne, Laurila, Kaija, Vornane, Martine, Nachmias Friedler, Vered, Morgenstern, Sara L, Amil Dias, Jorge, Carneiro, Fátima, Van Biervliet, Stephanie, Vande Velde, Saskia, Banoub, Hany, Sampson, Steve, Müller, Annette M, Ene, Adina, Rafeey, Mandana, and Eftekhar Sadat, Iran Amir Taher
Subjects: Male, Autoimmunity, ESPGHAN, nonbiopsy approach, ProCeDE study, adolescent, autoantibodies, biomarkers, biopsy, celiac disease, child, child preschool, Europe, female, GTP-binding proteins, HLA-DQ antigens, humans, immunoglobulin A, infant, intestine small, male, Middle East, molecular diagnostic techniques, predictive value of tests, prognosis, prospective studies, reproducibility of results, serologic tests, transglutaminases, Biopsy, gastroenterology, non-biopsy approach, HLA-DQ Antigens/genetics, 0302 clinical medicine, Immunoglobulin A/blood, Intestine, Small, Nonbiopsy Approach, Prospective Studies, Prospective cohort study, Child, education.field_of_study, medicine.diagnostic_test, Orvostudományok, Prognosis, Multicenter Study, medicine.anatomical_structure, Molecular Diagnostic Techniques, Transglutaminases/immunology, Predictive value of tests, Child, Preschool, 030211 gastroenterology & hepatology, Female, Intestine, Small/immunology, medicine.medical_specialty, Child, preschool, Adolescent, Anemia, Population, Celiac Disease/blood, Klinikai orvostudományok, 03 medical and health sciences, autoimmunity, proCeDE study, GTP-Binding Proteins, Predictive Value of Tests, 030225 pediatrics, Internal medicine, HLA-DQ Antigens, medicine, Journal Article, Humans, Protein Glutamine gamma Glutamyltransferase 2, Serologic Tests, Validation Studies, education, Pediatric gastroenterology, GTP-Binding Proteins/immunology, ProCeDE Study, Transglutaminases, business.industry, Infant, Reproducibility of Results, Hepatology, Endomysium, medicine.disease, Surgery, Immunoglobulin A, Celiac Disease, hepatology, business, Autoantibodies/blood, Biomarkers/blood
Abstract: Background & Aims The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. Methods We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. Results Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61–99.99); the PPV was 100.00 (95% CI, 98.68–100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67–99.96) to 100.00 (95% CI, 99.23–100.00). Conclusions Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.
Published: 2017

26. Rheumatoid arthritis phenotype at presentation differs depending on the number of autoantibodies present

Author: D. van der Woude, Ingiäld Hafström, Veerle F. A. M. Derksen, B. Svensson, Twj Huizinga, Sofia Ajeganova, René E. M. Toes, A.H.M. van der Helm-van Mil, Leendert A. Trouw, Clinical sciences, and Rheumatology
Subjects: Adult, Male, 0301 basic medicine, Arthritis, Rheumatoid/blood, Immunology, Blood Sedimentation, Disease, medicine.disease_cause, Peptides, Cyclic, General Biochemistry, Genetics and Molecular Biology, Autoimmunity, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Rheumatoid Factor, medicine, Humans, Immunology and Allergy, Rheumatoid factor, Alleles, Aged, Autoantibodies, Medicine(all), 030203 arthritis & rheumatology, medicine.diagnostic_test, biology, business.industry, Smoking, Age Factors, Autoantibody, Middle Aged, medicine.disease, Immunity, Humoral, Phenotype, 030104 developmental biology, Rheumatoid arthritis, Erythrocyte sedimentation rate, Peptides, Cyclic/immunology, Cohort, biology.protein, Female, Antibody, Autoantibodies/blood, Rheumatoid Factor/immunology, business
Abstract: ObjectivesIn rheumatoid arthritis (RA), seropositive and seronegative disease may be two entities with different underlying pathophysiological mechanisms, long-term outcomes and disease presentations. However, the effect of the conjoint presence of multiple autoantibodies, as proxy for a more pronounced humoral autoimmune response, on clinical phenotype remains unclear. Therefore, this study investigates the association between the number of autoantibodies and initial clinical presentation in two independent cohorts of patients with early RA.MethodsAutoantibody status (rheumatoid factor, anticitrullinated protein antibodies and anticarbamylated protein antibodies) was determined at baseline in the Leiden Early Arthritis Cohort (n=828) and the Swedish BARFOT (Better Anti-Rheumatic Farmaco-Therapy, n=802) study. The association between the number of autoantibodies and baseline clinical characteristics was investigated using univariable and multivariable ordinal regression.ResultsIn both cohorts, the following independent associations were found in multivariable analysis: patients with a higher number of RA-associated antibodies were younger, more often smokers, had a longer symptom duration and a higher erythrocyte sedimentation rate at presentation compared with patients with few autoantibodies.ConclusionsThe number of autoantibodies, reflecting the breadth of the humoral autoimmune response, is associated with the clinical presentation of RA. Predisease pathophysiology is thus reflected by the initial clinical phenotype.
Published: 2017

27. The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis

Author: Céline Lamacchia, Deshire Alpizar-Rodriguez, Pascal Zufferey, Michael John Nissen, Ines von Mühlenen, Ruediger B Mueller, Ulrich A. Walker, Delphine S. Courvoisier, Michael Mahler, Laure Brulhart, Adrian Ciurea, Burkhard Möller, Diego Kyburz, Axel Finckh, Sylvette Bas, Kim Lauper, Jean Dudler, Danielle Gascon, Cem Gabay, Pascale Roux-Lombard, University of Zurich, and Alpizar-Rodriguez, Deshire
Subjects: 0301 basic medicine, musculoskeletal diseases, Adult, Male, medicine.medical_specialty, 2745 Rheumatology, Population, 610 Medicine & health, Disease, Peptides, Cyclic, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Rheumatoid Factor, Interquartile range, immune system diseases, Risk Factors, Internal medicine, Epidemiology, medicine, Rheumatoid factor, Humans, education, skin and connective tissue diseases, Autoantibodies, Aged, 030203 arthritis & rheumatology, ddc:616, education.field_of_study, business.industry, Age Factors, 10051 Rheumatology Clinic and Institute of Physical Medicine, General Medicine, Middle Aged, medicine.disease, Arthritis, Rheumatoid/blood/immunology, 3. Good health, Rheumatoid Factor/blood, 030104 developmental biology, Rheumatoid arthritis, Immunology, Cohort, Peptides, Cyclic/immunology, Female, business, Autoantibodies/blood
Abstract: Transition from genetic risk to the development of systemic autoimmunity associated with rheumatoid arthritis (RA) is considered a key step for the development of RA and often referred to as the immune onset of the disease. The aim of this study is to identify predictors for the presence of anticitrullinated protein antibodies (ACPA) as a marker of systemic autoimmunity associated with RA in a high-risk population, an ongoing cohort of first-degree relatives of patients with RA. We assessed the presence of ACPA in individuals without clinical evidence of RA. We examined characteristics associated with ACPA positivity using general estimation equations to account for multiple observations per individual. A total of 1159 serum samples from 1025 subjects were analyzed, 69 samples (6%) were ACPA-positive, and 227 (20%) positive for rheumatoid factor. Participants had a median age of 45 years (interquartile range (IQR): 33-55) at baseline and 76% were women. Overall, ACPA positivity increased with age (p
Published: 2017

28. The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor

Author: A.H.M. van der Helm-van Mil, B. Svensson, Marije K. Verheul, Sofia Ajeganova, Ingiäld Hafström, Leendert A. Trouw, Twj Huizinga, K. Forslind, René E. M. Toes, H.W. van Steenbergen, Clinical sciences, and Rheumatology
Subjects: 0301 basic medicine, Male, Carbamates/immunology, Radiography, Gastroenterology, Arthritis, Rheumatoid, 0302 clinical medicine, Immunology and Allergy, Medicine, Longitudinal Studies, skin and connective tissue diseases, Medicine(all), education.field_of_study, biology, Middle Aged, Connective tissue disease, Rheumatoid Factor/blood, Rheumatoid arthritis, Peptides, Cyclic/immunology, Disease Progression, Female, Antibody, musculoskeletal diseases, Adult, medicine.medical_specialty, Arthritis, Rheumatoid/blood, Immunology, Population, Peptides, Cyclic, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Rheumatoid Factor, Internal medicine, Rheumatoid factor, Humans, Carp, education, Aged, Autoantibodies, 030203 arthritis & rheumatology, business.industry, Autoantibody, biology.organism_classification, medicine.disease, 030104 developmental biology, biology.protein, sense organs, Carbamates, Autoantibodies/blood, business
Abstract: ObjectiveAnti-carbamylated protein (anti-CarP) antibodies are reported to associate with more radiographic progression within the total rheumatoid arthritis (RA) population and anti-citrullinated peptide antibody (ACPA)-negative subgroup. We explored the association of anti-CarP with radiographic progression in RA and aimed to replicate the association and evaluate the added value of anti-CarP antibodies in relation to ACPA and rheumatoid factor (RF).Methods576 Swedish and 628 Dutch patients with RA (2394 and 3247 sets of radiographs, respectively) were longitudinally studied. Replication was restricted to the Swedish patients. In both cohorts, the association of anti-CarP with radiographic progression was determined in strata of patients with similar ACPA and RF status; results of both cohorts were combined in fixed-effect meta-analyses. The net percentage of patients for whom the radiographic progression in 5 years was additionally correctly classified when adding anti-CarP to a model including ACPA and RF was evaluated.ResultsAnti-CarP associated with radiographic progression in the total Swedish RA population (beta=1.11 per year, p=8.75×10−13) and in the ACPA-negative subgroup (beta=1.14 per year, p=0.034). Anti-CarP associated with more radiographic progression in the strata of ACPA-positive/RF-negative, ACPA-negative/RF-positive and ACPA-positive/RF-positive patients with RA (respective p values 0.014, 0.019 and 0.0056). A model including ACPA and RF correctly classified 54% and 57% of the patients; adding anti-CarP to this model did not increase these percentages (54% and 56% were correctly classified).ConclusionsAnti-CarP antibodies associated with more severe radiographic progression in the total and ACPA-negative RA population. Anti-CarP-positivity had a statistically significant additive value to ACPA and RF, but did not improve correct classification of patients.
Published: 2017

29. Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals: Results from the Danish Blood Donor Study

Author: Daniel Guldager Kring Rasmussen, Christian Erikstrup, Andreas S. Rigas, Morten Bagge Hansen, Lise Wegner Thørner, Ole Birger Pedersen, Klaus Rostgaard, Jakob Hjorth von Stemann, and Henrik Ullum
Subjects: Male, 0301 basic medicine, Physiology, Smoking/immunology, Denmark, medicine.medical_treatment, Test Statistics, lcsh:Medicine, Blood Donors, medicine.disease_cause, Body Mass Index, Autoimmunity, Habits, Mathematical and Statistical Techniques, 0302 clinical medicine, Reference Values, Seroepidemiologic Studies, Immune Physiology, Blood plasma, Medicine and Health Sciences, Smoking Habits, Medicine, lcsh:Science, Innate Immune System, education.field_of_study, Multidisciplinary, Obesity/immunology, biology, Smoking, Age Factors, Middle Aged, Body Fluids, Blood, C-Reactive Protein, Cytokine, Physiological Parameters, Physical Sciences, Regression Analysis, Cytokines, Female, Anatomy, Statistics (Mathematics), Research Article, Adult, Immunology, Population, Research and Analysis Methods, Blood Plasma, 03 medical and health sciences, Cytokines/immunology, Journal Article, Humans, Obesity, Statistical Methods, education, Autoantibodies, Behavior, business.industry, C-Reactive Protein/metabolism, Body Weight, C-reactive protein, lcsh:R, Autoantibody, Biology and Life Sciences, Molecular Development, Health Care, 030104 developmental biology, Immunoglobulin G/blood, Immune System, Immunoglobulin G, Etiology, biology.protein, lcsh:Q, Autoantibodies/blood, business, Body mass index, Mathematics, Developmental Biology, 030215 immunology
Abstract: Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c-aAb in question. A negative correlation between high levels of IL-6-specific c-aAb and plasma levels of C-reactive protein was observed, indicating cytokine-neutralizing levels of c-aAb in healthy blood donors. There was no substantial correlation between high levels of the five individual c-aAb investigated in this study. These data suggest that autoimmunity against endogenous cytokines is a relatively common phenomenon in healthy individuals, and that predictive factors for high, potentially neutralizing c-aAb levels vary depending on the cytokine in question, and may differ from predictors of general c-aAb presence.
Published: 2017

30. Serum levels of anti-apolipoprotein A-1 auto-antibodies and myeloperoxidase as predictors of major adverse cardiovascular events after carotid endarterectomy

Author: Domenico Palombo, Christophe Combescure, Aldo Pende, Nicolas Vuilleumier, Pascale Roux-Lombard, Sabrina Pagano, Fabrizio Montecucco, Franco Dallegri, Katia Galan, Giovanni Spinella, François Mach, Maria Bertolotto, and Bianca Pane
Subjects: Male, 0301 basic medicine, Apolipoprotein A-I/immunology, Time Factors, medicine.medical_treatment, Kaplan-Meier Estimate, Carotid endarterectomy, 030204 cardiovascular system & hematology, Severity of Illness Index, Likelihood ratios in diagnostic testing, Gastroenterology, Stroke/blood/etiology/immunology/mortality, 0302 clinical medicine, Risk Factors, Odds Ratio, Carotid Stenosis, Prospective Studies, Biological Markers/blood, Endarterectomy, ddc:616, Aged, 80 and over, Endarterectomy, Carotid, Likelihood Functions, Myeloperoxidase, Framingham Risk Score, Area under the curve, Hematology, Middle Aged, Stroke, Carotid Stenosis/blood/diagnosis/immunology/mortality/surgery, C-Reactive Protein, Treatment Outcome, Area Under Curve, Female, Endarterectomy, Carotid/adverse effects/mortality, carotid endarterectomy, Switzerland, carotid endarterectomy, anti-apolipoprotein A-1, Myeloperoxidase, Adverse cardiovascular events, Acute Coronary Syndrome/blood/etiology/immunology/mortality, medicine.medical_specialty, Adverse cardiovascular events, Peroxidase/blood, C-Reactive Protein/analysis, 03 medical and health sciences, Internal medicine, anti-apolipoprotein A-1, medicine, Humans, Acute Coronary Syndrome, ddc:576, Autoantibodies, Peroxidase, ddc:613, Aged, Apolipoprotein A-I, Receiver operating characteristic, business.industry, Odds ratio, Surgery, Logistic Models, 030104 developmental biology, ROC Curve, Autoantibodies/blood, business, Biomarkers, Mace
Abstract: SummaryWe aimed at challenging the prognostic accuracies of myeloperoxidase (MPO) and antibodies anti-apolipoprotein A-1 (anti-apoA-1 IgG), alone or in combination, for major adverse cardiovascular events (MACE) prediction, one year after carotid endarterectomy (CEA). In this prospective single centre study, 178 patients undergoing elective CEA were included. Serum anti-apoA-1 IgG and MPO were assessed by enzyme-linked immunosorbent assay prior to the surgery. Post-hoc determination of the MPO cut-off was performed by receiver operating characteristics (ROC) analyses. MACE was defined by the occurrence of fatal or non-fatal acute coronary syndromes or stroke during one year follow-up. Prognostic accuracy of anti-apoA-1 IgG was assessed by ROC curve analyses, survival analyses and reclassification statistics. During follow-up, 5% (9/178) of patients presented a MACE, and 29% (52/178) were positive for anti-apoA-1 IgG. Patients with MACE had higher median MPO and anti-apoA-1 IgG levels at admission (p=0.01), but no difference for the 10-year global Framingham risk score (FRS) was observed (p=0.22). ROC analyses indicated that both MPO and anti-apoA-1 IgG were significant predictors of subsequent MACE (area under the curve [AUC]: 0.75, 95% confidence interval [95%CI]: 0.61–0.89, p=0.01; and 0.74, 95%CI: 0.59–90; p=0.01), but combining anti-apoA-1 IgG positivity and MPO>857 ng/ml displayed the best predictive accuracy (AUC: 0.78, 95%CI: 0.65–0.91; p=0.007). It was associated with a poorer MACE-free survival (98.2% vs. 57.1%; p
Published: 2013
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31. DFS70 Autoantibodies are Rare in Healthy Danish Individuals but may Still Serve as a Diagnostic Aid

Author: Anne Voss, Søren Thue Lillevang, and Anna Christine Nilsson
Subjects: Male, business.industry, Denmark, Immunology, Adaptor Proteins, Signal Transducing/immunology, Autoantibody, General Medicine, Diagnostic aid, language.human_language, Autoimmune Diseases, Rheumatic Diseases/blood, Danish, Autoimmune Diseases/blood, Rheumatic Diseases, language, Medicine, Humans, Female, Transcription Factors/immunology, business, Autoantibodies/blood, Adaptor Proteins, Signal Transducing, Autoantibodies, Transcription Factors
Published: 2015

32. Anti-Apolipoprotein A-1 auto-antibodies are active mediators of atherosclerotic plaque vulnerability

Author: Fabrizio Montecucco, Nicolas Vuilleumier, Pascale Roux-Lombard, Vincent Braunersreuther, Franco Dallegri, Graziano Pelli, Giovanni Spinella, Bianca Pane, François Mach, Eniko Veronika Kovari, Sébastien Lenglet, Domenico Palombo, Maria Bertolotto, Aldo Pende, and Sabrina Pagano
Subjects: Male, Apolipoprotein A-I/immunology, ddc:616.07, 030204 cardiovascular system & hematology, Immunoglobulin G, anti-atherosclerotic treatment, Cohort Studies, ddc:616.89, Mice, 0302 clinical medicine, polycyclic compounds, Macrophage, Carotid Stenosis, Biological Markers/blood, ddc:616, 0303 health sciences, biology, Cytokines/metabolism, Plaque, Atherosclerotic, 3. Good health, Matrix Metalloproteinase 9, Plaque, Atherosclerotic/immunology, Cytokines, Female, lipids (amino acids, peptides, and proteins), Collagen, Matrix Metalloproteinase 9/metabolism, medicine.symptom, Cardiology and Cardiovascular Medicine, Carotid Artery, Internal, Carotid Stenosis/immunology, Enzyme-Linked Immunosorbent Assay, Inflammation, CCL2, 03 medical and health sciences, cannabinoid receptor, anti-Apolipoprotein A-1, atherosclerosis, In vivo, Collagen/metabolism, medicine, Animals, Humans, Interleukin 8, Autoantibodies, Aged, 030304 developmental biology, Apolipoprotein A-I, business.industry, nutritional and metabolic diseases, medicine.disease, Mice, Inbred C57BL, Atheroma, Immunoglobulin G/blood, Polyclonal antibodies, Immunology, biology.protein, Autoantibodies/blood, business, Biomarkers
Abstract: Aims Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability. Methods and results Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo , we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis ( n = 102) and in ApoE−/− mice infused with polyclonal anti-ApoA-1 IgG. In vitro , anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro , anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-α or CXCL8. Conclusion These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mice.
Published: 2011

33. Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children

Author: Patrice H. Lalive, B. C. Kieseier, H.-P. Hartung, Heinz Wiendl, M Schroeter, Y. Mikaeloff, Til Menge, Martin Häusler, H. Maurey, and Marc Tardieu
Subjects: Male, Epstein-Barr Virus Infections, Demyelinating Diseases/diagnosis/immunology, ddc:616.07, Myelin, 0302 clinical medicine, immune system diseases, Germany, Encephalitis, Viral, Biological Markers/blood, Child, Encephalomyelitis, Acute Disseminated/diagnosis/immunology, 0303 health sciences, biology, Encephalomyelitis, Acute Disseminated, Flow Cytometry, 3. Good health, Myelin-Associated Glycoprotein, Nerve Tissue Proteins/immunology, medicine.anatomical_structure, Neurology, Child, Preschool, Acute disseminated encephalomyelitis, Female, Transcription Factors/immunology, France, Myelin Proteins, Adolescent, Enzyme-Linked Immunosorbent Assay, Nerve Tissue Proteins, Encephalitis, Viral/diagnosis/immunology, Myelin oligodendrocyte glycoprotein, Diagnosis, Differential, 03 medical and health sciences, Predictive Value of Tests, medicine, Humans, Demyelinating Disorder, Autoantibodies, Retrospective Studies, 030304 developmental biology, Chi-Square Distribution, business.industry, Multiple sclerosis, Viral encephalitis, Myelin Basic Protein, medicine.disease, Virology, Oligodendrocyte, nervous system diseases, Immunity, Humoral, Myelin basic protein, Epstein-Barr Virus Infections/diagnosis/immunology, nervous system, Myelin-Associated Glycoprotein/immunology, Immunology, biology.protein, Myelin-Oligodendrocyte Glycoprotein, Neurology (clinical), Autoantibodies/blood, business, Biomarkers, 030217 neurology & neurosurgery, Demyelinating Diseases, Transcription Factors
Abstract: Background: Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibody frequencies have been variable across a number of studies and can also be detected in controls. Objective: To measure antibodies against MOG in paediatric patients with demyelinating disorders of the central nervous system and in controls. Methods: Serum antibodies against MOG and myelin basic protein were measured by ELISA, flow cytometry (FACS) and in the liquid phase in 11 children with acute disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with acute viral encephalitis and 13 healthy controls. The serostatus of Epstein–Barr virus (EBV) infections were assessed. Results: Anti-MOG antibodies, measured either by ELISA or FACS were exclusively detected in children with demyelination. In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable equally in all groups. The presence of either autoantibodies did not associate with EBV serostatus, age, gender or disease course. Conclusions: This study independently corroborates recently published results of seroprevalence and specificity of the assay. Due to their low sensitivity anti-MOG antibodies will not serve as disease-specific biomarkers, but could help to support the diagnosis of ADEM in difficult cases.
Published: 2011
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34. Simultaneous Measurement of Plasma Concentrations of Proinsulin and C-Peptide and Their Ratio with a Trefoil-Type Time-Resolved Fluorescence Immunoassay

Author: Evilien Vekens, Ilse Vermeulen, I. Truyen, Pieter De Pauw, Daniel Pipeleers, Farah T. van Genderen, Ogonnaya C. Ubani, Frans Gorus, Joeri W. De Grijse, Chris Van Schravendijk, Pathology/molecular and cellular medicine, Medical Biochemistry, Faculty of Medicine and Pharmacy, and Pathologic Biochemistry and Physiology
Subjects: Heterophile, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Prohormone, Fluorescent Antibody Technique, Peptide, Peptide hormone, digestive system, chemistry.chemical_compound, medicine, Humans, Multiplex, Autoantibodies, Proinsulin, chemistry.chemical_classification, Chromatography, C-Peptide, medicine.diagnostic_test, C-peptide, Biochemistry (medical), Antibodies, Monoclonal, Proinsulin/blood, Diabetes Mellitus, Type 1, chemistry, Biochemistry, Immunoassay, C-Peptide/blood, Diabetes Mellitus, Type 1/diagnosis, Autoantibodies/blood, medicine.drug
Abstract: Background: When the concentrations of 2 or more substances are measured separately, their molar ratios are subject to the additive imprecisions of the different assays. We hypothesized that the cumulative error for concentration ratios of peptides containing a common sequence might be minimized by measuring the peptides simultaneously with a “trefoil-type” immunoassay. Methods: As a model of this approach, we developed a dual-label time-resolved fluorescence immunoassay (TRFIA) to simultaneously measure proinsulin, C-peptide, and the proinsulin–C-peptide ratio (PI/C). A monoclonal antibody captures all C-peptide–containing molecules, and 2 differently labeled antibodies distinguish between proinsulin-like molecules and true C-peptide. Results: The trefoil-type TRFIA was capable of measuring plasma C-peptide and proinsulin simultaneously without mutual interference at limits of quantification of 48 and 8125 pmol/L, and 2.1 and 197 pmol/L, respectively. Within-laboratory imprecision values for the trefoil-type TRFIA ranged between 8.4% and 12% for the hormone concentrations. Unlike the hormone results obtained with separate assays, imprecision did not increase when PI/C was calculated from trefoil assay results (P < 0.05). Peptide concentrations were highly correlated with results obtained in individual comparison assays (r2 ≥ 0.965; P < 0.0001). The total error for PI/C obtained with the trefoil-type TRFIA remained ≤25% over a broader C-peptide range than with separate hormone assays (79–7200 pmol/L vs 590–4300 pmol/L C-peptide). Preliminary data indicate little or no interference by heterophile antibodies. Conclusions: The developed trefoil-type TRFIA is a reliable method for simultaneous measurement of proinsulin, C-peptide, and PI/C and provides proof of principle for the development of other trefoil-type multiple-label immunoassays.
Published: 2008

35. HLA-DR Expressing Peripheral T Regulatory Cells in Newly Diagnosed Patients with Different Forms of Autoimmune Thyroid Disease

Author: Agathocles Tsatsoulis, G. Philippou, George Vartholomatos, Stathis Frillingos, Nikolaos Kolaitis, and Stelios Fountoulakis
Subjects: Adult, Male, Thyroid Hormones, Endocrinology, Diabetes and Metabolism, Interleukin-2 Receptor alpha Subunit/metabolism, Population, Hashimoto Disease, Newly diagnosed, T-Lymphocytes, Regulatory, Thyroiditis, Flow cytometry, Pathogenesis, Young Adult, HLA-DR Antigens/*metabolism, Hashimoto Disease/blood/*immunology, Endocrinology, T-Lymphocyte Subsets, medicine, HLA-DR, Humans, IL-2 receptor, education, T-Lymphocytes, Regulatory/*immunology, Autoantibodies, education.field_of_study, medicine.diagnostic_test, business.industry, Interleukin-2 Receptor alpha Subunit, HLA-DR Antigens, Middle Aged, Flow Cytometry, medicine.disease, T-Lymphocyte Subsets/immunology, Thyroid Hormones/blood, Graves Disease, Peripheral, Graves Disease/blood/*immunology, Case-Control Studies, Immunology, Female, Autoantibodies/blood, business
Abstract: BACKGROUND: Several reports have claimed a role for T regulatory cells (Tregs) in the pathogenesis of various autoimmune diseases, including autoimmune thyroid disease (AITD). The aim of the present study was to examine whether changes in the number of peripheral CD4 + CD25highHLA-DR + lymphocytes, a subpopulation of Tregs, occur in patients with AITD. METHODS: Three-color flow cytometry was used to detect the proportion of CD4 cells expressing CD25, CD25high, and HLA-DR in 70 newly diagnosed and untreated AITD patients and 20 controls. The intensity of CD25 expression on these cells was also examined. RESULTS: The proportion of CD4 + CD25 + cells as well as the proportion of CD4 + CD25high cells among the population of CD4 lymphocytes was not different in AITD patients relative to controls. However, a significant increase in the proportion of CD4 + CD25highHLA-DR + cells among the population of CD4 lymphocytes was found in patients with Hashimoto's thyroiditis (HT) compared to controls. CONCLUSIONS: In HT patients there is a quantitative increase of CD4 + CD25highHLA-DR + cells that may indicate a compensatory expansion of this subpopulation of Tregs in an attempt to suppress the immune response. Thyroid
Published: 2008

36. Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis

Author: Gottenberg, J E, Courvoisier, D S, Hernandez, M V, Iannone, F, Lie, E, Canhão, H, Pavelka, K, Hetland, M L, Turesson, C, Mariette, X, and Finckh, Axel
Subjects: musculoskeletal diseases, ddc:616, Male, Cyclic/immunology, Arthritis, Antirheumatic Agents/therapeutic use, Middle Aged, Peptides, Cyclic, Abatacept, Arthritis, Rheumatoid, Europe, Abatacept/therapeutic use, Rheumatoid Factor/blood, Treatment Outcome, Predictive Value of Tests, Rheumatoid Factor, Antirheumatic Agents, Humans, Female, Rheumatoid/blood/drug therapy, Registries, skin and connective tissue diseases, Autoantibodies/blood, Peptides, Autoantibodies
Abstract: To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA).We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated.We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P0.001 and HR 0.78 [95% CI 0.68-0.90], P0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P0.001).Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.
Published: 2015

37. Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid factors, and erosive joint disease in patients with early, untreated rheumatoid arthritis

Author: N. H. H. Heegaard, Ulrik Tarp, Kim Hørslev-Petersen, Hanne Merete Lindegaard, I. Hansen, Peter Junker, Peter Garred, Jan Pødenphant, Anders Jørgen Svendsen, Torkell Ellingsen, Merete Lund Hetland, Mikkel Østergaard, Kristian Stengaard-Pedersen, L.S. Andersen, Tine Lottenburger, J. K. Pedersen, Ho Madsen, A Krol, Søren Jacobsen, and Anne Friesgaard Christensen
Subjects: Male, Arthritis, Epitopes/immunology, Disease, Gastroenterology, Epitope, Arthritis, Rheumatoid, Epitopes, Risk Factors, Seroepidemiologic Studies, Immunoglobulin A/blood, Prevalence, Immunology and Allergy, skin and connective tissue diseases, biology, Smoking, General Medicine, Smoking/epidemiology, Middle Aged, Rheumatoid Factor/blood, Rheumatoid arthritis, Peptides, Cyclic/immunology, Female, Antibody, musculoskeletal diseases, Adult, medicine.medical_specialty, Joints/immunology, Arthritis, Rheumatoid/blood, Immunology, Peptides, Cyclic, Young Adult, Rheumatology, Rheumatoid Factor, Internal medicine, medicine, Rheumatoid factor, Humans, Autoantibodies, Aged, business.industry, Odds ratio, medicine.disease, Immunoglobulin M/blood, Immunoglobulin A, Immunoglobulin M, biology.protein, Joints, business, Autoantibodies/blood
Abstract: OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset.METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity.RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes.CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.
Published: 2015

38. Rheumatoid arthritis

Author: Ajeganova, Sofia, Huizinga, Tom W J, and Rheumatology
Subjects: Medicine(all), Treatment Outcome, Arthritis, Rheumatoid/drug therapy, Combined Modality Therapy/methods, Seroepidemiologic Studies, Canada/epidemiology, Cohort studies, Humans, Antirheumatic Agents/therapeutic use, Prospective Studies, Autoantibodies/blood, Prognosis, Rheumatoid Factor/immunology
Published: 2015

39. The effects of rheumatoid factor and anticitrullinated peptide antibodies on bone erosions in rheumatoid arthritis

Author: H.W. van Steenbergen, A.H.M. van der Helm-van Mil, Kristina Forslind, Sofia Ajeganova, B Svensson, Clinical sciences, and Rheumatology
Subjects: musculoskeletal diseases, Male, Pathology, medicine.medical_specialty, Arthritis, Rheumatoid/immunology, Immunology, Peptide, Vimentin, Peptides, Cyclic, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, Rheumatology, Rheumatoid Factor, immune system diseases, Bone cell, medicine, Immunology and Allergy, Rheumatoid factor, Humans, In patient, skin and connective tissue diseases, Autoantibodies, chemistry.chemical_classification, Medicine(all), biology, business.industry, Autoantibody, medicine.disease, chemistry, Rheumatoid arthritis, Peptides, Cyclic/immunology, biology.protein, Female, Antibody, business, Autoantibodies/blood, Rheumatoid Factor/immunology
Abstract: With interest we read the article by Hecht et al 1 who studied the associations of anticitrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) with bone erosions in rheumatoid arthritis (RA). The background of this study was that ACPAs directed against citrullinated vimentin induce differentiation of osteoclasts, indicating that ACPA has a direct effect on bone resorption.2 No biological data are available on whether RF also affects bone cells and, given the overlap between ACPA-positivity and RF-positivity, the authors wanted to distinguish the association between RF and bone erosions from the association between ACPA and bone erosions. In a cross-sectional study, high-resolution peripheral quantitative CT (HR-pQCT) images of metacarpophalangeal (MCP) 2–4 joints of 238 patients with RA were made and groups of patients with different combinations of autoantibodies were compared. The authors observed mainly differences in erosive burden in patients with both antibodies compared with those without antibodies. In a subgroup analysis, they also reported a higher erosive burden in ACPA+/RF+ patients compared with ACPA+/RF− patients. Based on their findings the authors suggested that RF may act as an enhancer of bone loss in ACPA-positive patients. HR-pQCT is an interesting tool that admits …
Published: 2015

40. Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis

Author: Roger Hesselstrand, Niels Hh Heegaard, Gabriel N. Teku, Samantha O. Steen, Anting Liu Carlsen, Marie Wildt, Dirk M. Wuttge, and Mauno Vihinen
Subjects: Male, Adult, Pathology, medicine.medical_specialty, systemic sclerosis, RNA Polymerase III/immunology, systemic sclerosis scleroderma micro-RNA autoantibody plasma GLOMERULAR-FILTRATION-RATE LUPUS-ERYTHEMATOSUS EXPRESSION CLASSIFICATION SCLERODERMA, Disease, Systemic scleroderma, Scleroderma, Rheumatology, RNA, Small Nuclear, Scleroderma, Systemic/blood, microRNA, medicine, Humans, scleroderma, Pharmacology (medical), skin and connective tissue diseases, plasma, Autoantibodies, Aged, Rheumatology and Autoimmunity, DNA Topoisomerases, Type I/immunology, Sweden, Scleroderma, Systemic, RNA, Small Nuclear/immunology, integumentary system, business.industry, micro-RNA, Autoantibody, RNA Polymerase III, MicroRNAs/blood, Middle Aged, medicine.disease, Phenotype, MicroRNAs, Cross-Sectional Studies, DNA Topoisomerases, Type I, Immunology, Regression Analysis, Female, Autoantibodies/blood, business, autoantibody
Abstract: Objective. To evaluate the expression profiles of cell-free plasma miRNAs in SSc and to characterize their correlation with disease subgroups (lcSSc and dcSSc) and with autoantibody profiles.Methods. Using quantitative RT-PCR, the abundance of 45 mature miRNAs in plasma was determined in 95 patients (lcSSc = 63; dcSSc = 32), representing the following autoantibody subgroups: ACA, anti-DNA topoisomerase I, anti-RNA polymerase III and anti-U1-ribonucleoprotein. MiRNA data were correlated with clinical and paraclinical data. Multiple regression was used to model membership of the lcSSc, dcSSc and autoantibody subgroups, based on miRNA expression profiles.Results. Thirty-six miRNAs were measurable in all samples. Four (miRNA-223, -181b, -342-3p and -184) were differently expressed in lcSSc and dcSSc (false discovery rate < 0.05). Ten miRNAs exhibited statistically significantly different levels in one or more autoantibody groups, and five (miRNA-409, -184, -92a, -29a and -101) remained significant after correction for multiple comparisons. Multiple regression models accurately predicted ACA and anti-DNA topoisomerase I antibody-positive patients (area under the curve (AUC) = 0.97 and 0.93, respectively) as well as membership of the dcSSc and lcSSc groups (AUC = 0.88).Conclusion. Circulating miRNA profiles differ between lcSSc and dcSSc patients and between patients with different autoantibodies. This is the first time autoantibody profiles, disease phenotypes and plasma miRNA profiles have been shown to correlate in an autoimmune disease. The data support a pathobiological role of miRNAs because specific miRNAs associate with autoantibody profiles of known diagnostic and prognostic value.
Published: 2015

41. Proinsulin levels and the proinsulin:c-peptide ratio complement autoantibody measurement for predicting type 1 diabetes

Author: E. Vandemeulebroucke, P. De Pauw, F. K. Gorus, Ogonnaya C. Ubani, Rui Mao, I. Truyen, C. Van Schravendijk, K. Decochez, I Weets, Daniel Pipeleers, P. N. Jørgensen, Pathologic Biochemistry and Physiology, Electrical Engineering and Power Electronics, Department of Bio-engineering Sciences, Ultrastructure, Structural Biology Brussels, and Experimental Pharmacology
Subjects: Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Prohormone, medicine.disease_cause, HLA-DQ Antigens/genetics, Autoimmunity, chemistry.chemical_compound, Child, Proinsulin, C-Peptide, biology, C-peptide, Middle Aged, Pedigree, C-Peptide/blood, Female, Antibody, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, endocrine system, medicine.medical_specialty, Child, preschool, digestive system, Prediabetic State, Islets of Langerhans, Predictive Value of Tests, HLA-DQ Antigens, Internal medicine, HLA-DQ, Internal Medicine, medicine, Humans, Islets of Langerhans/immunology, Autoantibodies, Type 1 diabetes, Prediabetic State/diagnosis, Infant, Newborn, Autoantibody, Infant, nutritional and metabolic diseases, Diabetes Mellitus, Type 1/blood, medicine.disease, Hormones, Hormones/blood, Proinsulin/blood, Diabetes Mellitus, Type 1, Endocrinology, chemistry, Immunology, biology.protein, Autoantibodies/blood
Abstract: AIMS/HYPOTHESIS: We investigated whether random proinsulin levels and proinsulin:C-peptide ratio (PI:C) complement immune and genetic markers for identifying relatives at high risk of type 1 diabetes. MATERIALS AND METHODS: During an initial sampling, random glycaemia, proinsulin, PI:C and HLA DQ genotype were determined in 561 non-diabetic first-degree relatives who had been positive for islet autoantibodies on one or more occasions and in 561 age- and sex-matched persistently antibody-negative relatives. RESULTS: During follow-up (median 62 months), 46 relatives with antibodies at entry developed type 1 diabetes. At baseline, antibody-positive relatives (n=338) had higher PI:C values (p
Published: 2005

42. Anti‐protein S antibodies following a varicella infection: detection, characterization and influence on thrombin generation

Author: Thomas Lecompte, P. G. De Groot, Hulya Ozsahin, P. De Moerloose, Véronique Regnault, Françoise Boehlen, and Denis Wahl
Subjects: Male, Protein S Deficiency, Time Factors, IgA Vasculitis, Enzyme-Linked Immunosorbent Assay, Purpura, Schoenlein-Henoch/etiology/virology, Protein S, Epitope, Chickenpox/blood/complications, Tissue factor, Chickenpox, Protein S/immunology, Thrombin, Protein S Deficiency/etiology/virology, medicine, Thrombophilia, Humans, Protein S deficiency, Autoantibodies, ddc:616, ddc:618, biology, business.industry, Hematology, Surface Plasmon Resonance, medicine.disease, Virology, Molecular biology, Thrombin/biosynthesis, Child, Preschool, biology.protein, Antibody, Autoantibodies/blood, business, Thrombophilia/etiology/virology, Epitope Mapping, Protein C, medicine.drug, Purpura fulminans
Abstract: Postinfectious purpura fulminans is a rare disease. Varicella is one of the precipitating conditions and we recently observed such a case. The 4-year-old child was found to have a severe transient protein S deficiency. By enzyme-linked immunosorbent assay and surface plasmon resonance we first demonstrated that anti-protein S antibodies were present and also transient. Next we characterized the epitopes against which these antibodies were directed and found that they predominantly recognized the N-terminal part of protein S. Finally we showed by thrombography a transient dramatic hypercoagulable state as a result of thrombin being unregulated by the dynamic protein C inhibitory system: in vitro thrombin generation, in response to a low concentration of tissue factor, was almost insensitive to activated protein C up to 25 nmol L(-1) on day 4 while it was normally sensitive on day 42. For the first time, we demonstrated a temporal relationship between protein S deficiency, antibodies to protein S and hypercoagulability, thus supporting the pathogenic role of these antibodies.
Published: 2005

43. Serum matrix metalloproteinase‐9 is elevated in men with a history of myocardial infarction

Author: Anne Kalela, Matti Höyhtyä, Jaana Renko, O. Jaakkola, H. Alho, Seppo T. Nikkari, and Seppo Laine
Subjects: Male, Clinical Biochemistry, Myocardial Infarction, 030204 cardiovascular system & hematology, Lipoproteins, LDL/immunology, Logistic regression, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Myocardial infarction, Complement C3/analysis, Finland, 2. Zero hunger, Cholesterol, HDL/blood, Statistics, Smoking, Complement C3, General Medicine, Middle Aged, Lipoproteins, LDL, Triglycerides/blood, C-Reactive Protein, Cholesterol, Matrix Metalloproteinase 9, HDL/blood, LDL/immunology, lipids (amino acids, peptides, and proteins), Matrix Metalloproteinase 9/blood, medicine.medical_specialty, Lipoproteins, Cholesterol/blood, Statistics, Nonparametric, C-Reactive Protein/analysis, 03 medical and health sciences, Internal medicine, medicine, Humans, Nonparametric, Triglycerides, Autoantibodies, Aged, Triglyceride, business.industry, Cholesterol, HDL, Autoantibody, medicine.disease, Coronary heart disease, Cross-Sectional Studies, Logistic Models, Endocrinology, chemistry, Autoantibodies/blood, Myocardial Infarction/blood, business, Body mass index, 030217 neurology & neurosurgery, Lipoprotein
Abstract: Elevated serum inflammatory markers have been reported in coronary heart disease. Levels of serum matrix metalloproteinase‐9 (MMP‐9), C‐reactive protein (CRP), C3‐complement (C3) and autoantibodies against oxidized low‐density lipoprotein (oxLDL) in 120 male subjects with a history of myocardial infarction (MI) were compared with those in 250 age‐matched controls, both groups from a large cross‐sectional population survey, the FINRISK study. The concentrations of serum MMP‐9 and autoantibodies against oxLDL were measured by enzyme‐linked immunosorbent assay, CRP and C3 by immunonephelometry. MMP‐9, CRP and C3 concentrations were higher in the subjects with a history of MI than in the controls (p=0.037, p=0.004, and p=0.006, respectively). There was no difference between the groups in serum levels of autoantibodies against oxLDL. In other background characteristics, men in the MI group had higher body mass index (BMI) and serum triglyceride values and lower serum HDL cholesterol values compared to controls (p=0.009, p=0.001, and p
Published: 2004

44. Thyroid disorders in patients with newly diagnosed rheumatoid arthritis is associated with poor initial treatment response evaluated by disease activity score in 28 joints-C-reactive protein (DAS28-CRP)

Author: Jørgen Hangaard, Inger Marie Jensen Hansen, and Amir Emamifar
Subjects: rheumatoid arthritis, Male, 0301 basic medicine, Pathology, Anti-nuclear antibody, Denmark, Antirheumatic Agents/therapeutic use, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Thyroid Diseases/blood, IgM RF, Prevalence, Joints/pathology, Registries, biology, Thyroid, DAS28-CRP, General Medicine, Middle Aged, ANA, anti-CCP, thyroid disorders, Rheumatoid Factor/blood, Treatment Outcome, medicine.anatomical_structure, Rheumatoid arthritis, Peptides, Cyclic/immunology, Female, Cohort study, medicine.medical_specialty, Arthritis, Rheumatoid/blood, C-Reactive Protein/analysis, 03 medical and health sciences, Internal medicine, medicine, Humans, Rheumatoid factor, Aged, 030203 arthritis & rheumatology, Antibodies, Antinuclear/blood, business.industry, C-reactive protein, Immunoglobulin M/blood, medicine.disease, Rheumatology, 030104 developmental biology, biology.protein, Autoantibodies/blood, business, Rheumatism
Abstract: To determine the prevalence of thyroid disorders among newly diagnosed rheumatoid arthritis (RA) patients and evaluate the association between clinical characteristics of RA and thyroid disorders, and also initial treatment response in the RA patients with thyroid disorders. Newly diagnosed, adult RA patients who were diagnosed according to the new 2010 American College of Rheumatology/European League Against Rheumatism criteria since January 1, 2010, were included. Patients’ demographic data, serology results including immunoglobulin M rheumatoid factor (IgM RF), anticyclic citrullinated peptide antibody (anti-CCP), and antinuclear antibody (ANA), and also disease activity score in 28 joints-C-reactive protein at the time of diagnosis and after 4 months (±1–2 months) of treatment initiation were extracted from Danish Danbio Registry. Patients’ electronic hospital records for the past 10 years were reviewed to reveal if they had been diagnosed with thyroid disorders or they had abnormal thyroid test. In all, 439 patients were included, female 60.1%, mean age 64.6 ± 15.0 years and disease duration 2.6 ± 1.7 years. Prevalence of thyroid disorders was 69/439 (15.7%) and hypothyroidism was the most frequent disorder (30.4%). The presence of thyroid disorders among RA patients was significantly associated with female sex (P
Published: 2017

45. Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis

Author: Kim Hørslev-Petersen, Malene Hvid, Bent Deleuran, Peter Junker, Kristian Stengaard-Pedersen, Mikkel Østergaard, Julie Kristine Laustsen, Tue Kruse Rasmussen, and Merete Lund Hetland
Subjects: Male, Leukocytes, Mononuclear/metabolism, Time Factors, T-Lymphocytes, Arthritis, Antirheumatic Agents/therapeutic use, Monocytes, Synovial Fluid/metabolism, Arthritis, Rheumatoid, Monocytes/metabolism, Synovial Fluid, Immunology and Allergy, B-Lymphocytes, biology, Middle Aged, Flow Cytometry, T-Lymphocytes/metabolism, Receptors, OX40/blood, Treatment Outcome, Antibodies, Monoclonal, Humanized/therapeutic use, Antirheumatic Agents, Rheumatoid arthritis, Peptides, Cyclic/immunology, Female, Antibody, Research Article, medicine.drug, Adult, medicine.medical_specialty, OX40 Ligand/blood, Methotrexate/therapeutic use, Arthritis, Rheumatoid/blood, Immunology, OX40 Ligand, Enzyme-Linked Immunosorbent Assay, Antibodies, Monoclonal, Humanized, Peptides, Cyclic, Rheumatology, Internal medicine, medicine, Adalimumab, Humans, Synovial fluid, B-Lymphocytes/metabolism, Autoantibodies, Aged, business.industry, Autoantibody, Receptors, OX40, medicine.disease, Methotrexate, Endocrinology, Solubility, Leukocytes, Mononuclear, biology.protein, Autoantibodies/blood, business
Abstract: Introduction OX40 and its ligand OX40L are key components in the generation of adaptive memory response and provide necessary co-stimulatory signals for activated effector T cells. Here we investigate the dual roles of the membrane and soluble (s) forms of OX40 and OX40L in plasma and synovial fluid and their association with autoantibodies and disease activity in rheumatoid arthritis (RA). Methods Soluble OX40 and sOX40L plasma levels were measured in treatment-naïve early RA patients (eRA) at baseline and after 3, 6, and 12 months of treatment with methotrexate and adalimumab (n = 39) and with methotrexate alone (n = 37). Adalimumab was discontinued after the first year, and patients were followed for additional 12 months. For comparison, sOX40 and sOX40L were measured in patients with chronic RA (cRA, n = 15) and healthy volunteers (HV, n = 34). Membrane-bound OX40 and OX40L expression on T cells, B cells and monocytes were quantified. Results Soluble OX40 plasma levels of eRA patients were not different at the time of treatment initiation, but were significantly higher after 12 months of treatment, compared with HV or cRA patients. Soluble OX40L was significantly elevated throughout the first 12 months of treatment compared with HVs and patients with cRA. Adalimumab treatment did not influence sOX40 or sOX40L plasma levels. At baseline, sOX40L levels were strongly associated with the presence of anti-citrullinated protein antibodies (ACPA) (P
Published: 2014

46. Multifocal motor neuropathy with high titers of anti-MAG antibodies

Author: Bridel, Claire, Horvath, Judit, Kurian, Mary, Truffert, André, Steck, Andreas, and Lalive d'Epinay, Patrice
Subjects: Polyneuropathies/blood/complications/immunology, Myelin Sheath/metabolism/pathology, Intermediate Filaments/metabolism, Intermediate Filaments, Neural Conduction, Paraproteinemias, Middle Aged, Paraproteinemias/blood/complications/immunology, ddc:616.8, Myelin-Associated Glycoprotein, Polyneuropathies, Immunoglobulin M, Myelin-Associated Glycoprotein/immunology, Humans, Female, Immunoglobulin M/metabolism, Autoantibodies/blood, Myelin Sheath, Autoantibodies
Abstract: Multifocal motor neuropathy (MMN) and anti-myelin-associated glycoprotein (anti-MAG)-associated neuropathy are clinically and electrophysiologically distinct entities. We describe a patient with characteristic features of both neuropathies, raising the possibility of an overlap syndrome. A 49-year-old patient reported a history of slowly progressive predominantly distal tetraparesis, with mild sensory deficits. Nerve conduction studies demonstrated persistent motor conduction blocks outside compression sites, typical of MMN. Laboratory findings revealed persistently high titers of anti-MAG immunoglobulin Mλ (IgMλ) paraprotein in the context of a monoclonal gammapathy of unknown significance. Skin biopsy of distal lower limb revealed IgM positive terminal nerve perineurium deposits. This case suggests that the distinction between subtypes of chronic inflammatory neuropathies may not be as clear as initially thought, and that the pattern of pathogenicity of anti-MAG antibodies may vary.
Published: 2014

47. Quantification of EGFR autoantibodies in the amplification phenomenon of HER2 in breast cancer

Author: Dorte Aa. Olsen, Ivan Brandslund, and Erik Jakobsen
Subjects: Adult, Receptor, ErbB-2, EGFR, Clinical Biochemistry, Blotting, Western, Breast Neoplasms, Enzyme-Linked Immunosorbent Assay, Biology, ErbB2 gene amplification, Breast cancer, ErbB Receptors/immunology, Gene duplication, Breast Neoplasms/blood, ERBB2 Gene Amplification, medicine, Humans, Receptor, skin and connective tissue diseases, Autoantibodies, Aged, Aged, 80 and over, medicine.diagnostic_test, Biochemistry (medical), Autoantibody, Cancer, General Medicine, Middle Aged, medicine.disease, Molecular biology, Receptor, ErbB-2/genetics, ErbB Receptors, Immunohistochemistry, ELISA, Female, Autoantibodies/blood, Fluorescence in situ hybridization
Abstract: Background Gene amplification of HER2 (human epidermal growth factor receptor 2) is a well-known phenomenon in various cancers. However, little is known about the mechanism of the gene amplification phenomenon itself. Autoantibodies to cellular receptors have been described in several cancer types. We hypothesised that autoantibodies against HER2 might have a stimulatory capacity and could be the cause of the HER2 gene amplification phenomenon. To investigate this, we developed a test for the detection of autoantibodies against HER2 in serum (S-HER2Ab). Methods Blood and tissue samples were collected from 311 women consecutively admitted for surgical treatment of primary breast cancer. Paraffin embedded tissue sections were analysed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 protein concentrations in tissue were determined in 115 patients. Circulating extracellular domain of HER2 (S-HER2) was measured using the Advia Centaur (Siemens AG, Munich, Germany). Analysis for autoantibodies was developed on an ImmunoCAP 100 (Phadia AB, Uppsala, Sweden) with an automated Fluorescent Enzyme Immuno Assay. Results Of 311 women, 55 (17.7%) had HER2Ab and 51 (16.4%) showed amplification of the HER2 gene determined by IHC/FISH. Eleven women had detectable S-HER2Ab as well as HER2 gene amplification, but no statistically significant correlation was found between the two phenomena. A significantly higher level of S-HER2Ab was found both in HER2 gene-amplified and non-amplified breast cancer patients compared to an age-matched healthy control group. No statistically significant difference in presence or concentration of S-HER2Ab was found in HER2 gene-amplified vs. non-amplified breast cancer. Conclusions S-HER2Ab can be measured accurately with the ImmunoCAP 100. There is an increased prevalence and concentration of S-HER2Ab in breast cancer patients but no correlation with HER2 gene amplification. We conclude that autoantibodies against HER2 do not seem to be the cause of HER2 gene amplification.
Published: 2013

48. Orodigital Pemphigus Vulgaris

Author: Emmanuel Laffitte, Renato G. Panizzon, Luca Borradori, and University of Groningen
Subjects: Paronychia/immunology, Desmoglein 1/immunology, NAIL INVOLVEMENT, medicine.disease_cause, PHENOTYPE, Autoimmunity, PALMOPLANTAR KERATODERMA, Immunopathology, FOLIACEUS, Anti-desmoglein-1 and-3 antibodies, Biological Markers/blood, Paronychia, education.field_of_study, Mouth Mucosa/pathology, integumentary system, Desmoglein 3, Desmoglein 1, Middle Aged, Pemphigus/immunology/pathology, Female, medicine.medical_specialty, Mouth Diseases/immunology/pathology, Enzyme-Linked Immunosorbent Assay, Dermatology, Desmoglein, Pemphigus antibodies, Fingers, medicine, Humans, education, Aged, Autoantibodies, LESIONS, business.industry, Pemphigus vulgaris, Mouth Mucosa, Toes, medicine.disease, Desmoglein 3/immunology, GENE, ddc:616.8, Pemphigus, Immunology, business, Autoantibodies/blood, Mouth Diseases, Biomarkers
Abstract: Paronychia is a rare complication of pemphigus vulgaris (PV), and the immunological profile of patients with digital disease has not been assessed so far. We report 2 cases of PV with oral mucosa and periungual involvement, who had high titers of anti-desmoglein (Dsg)-3 circulating antibodies. These observations raise the possibility that expression of Dsg-1 and Dsg-3 in distinct areas of periungual skin is disease specific and that anti-Dsg-3 antibodies alone may have an as yet unrecognized importance for the development of paronychia in PV. Copyright (c) 2008 S. Karger AG, Basel
Published: 2008

49. HLA-DRB1 and HLA-DQB1 allele associations in an Albanian patient population with rheumatoid arthritis: correlations with the specific autoantibody markers and inter-population DRB1 allele frequency variability

Author: Margarita Prifti-Kurti, Zamira Ylli, Erkena Shyti, Jose Manuel Nunes, G. Sulcebe, and Alicia Sanchez-Mazas
Subjects: Male, Arthritis, Rheumatoid, ddc:590, Gene Frequency, immune system diseases, Risk Factors, Prevalence, Immunology and Allergy, Medicine, HLA-DQ beta-Chains, European Continental Ancestry Group/genetics, HLA-DRB1 Chains/genetics, skin and connective tissue diseases, HLA-DRB1, education.field_of_study, HLA-DQB1, Rheumatoid/blood/diagnosis/ethnology/genetics/immunology, Middle Aged, Rheumatoid Factor/blood, Phenotype, Albania, Female, musculoskeletal diseases, Adult, Cyclic/immunology, Immunology, Population, Context (language use), Human leukocyte antigen, Peptides, Cyclic, White People, Rheumatology, Rheumatoid Factor, Rheumatoid factor, Humans, Genetic Predisposition to Disease, Allele, education, Allele frequency, Autoantibodies, Albania/epidemiology, business.industry, Arthritis, Protective Factors, HLA-DQ beta-Chains/genetics, Case-Control Studies, Autoantibodies/blood, Peptides, business, Biomarkers/blood, Biomarkers, HLA-DRB1 Chains
Abstract: The prevalence of rheumatoid arthritis and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with rheumatoid arthritis (RA), and taking into account their rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA) serologic subgroups, we compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. No differences were found between the controls and the RA patient group as a whole, but three statistically significant differences were found: an increase in DRB1*04 among ACPA+, RF+ and ACPA+/RF+ patients, a significant decrease in DRB1*11 among ACPA+/RF+ and also a decrease in DRB1*13 among RF+ patient subgroups. Comparing allele frequencies of putatively associated RA alleles in different European populations revealed a significant negative correlation between the RA predisposing DRB1*04 and protective DRB1*11 allele frequencies. A statistically significant correlation was also found between RA prevalence rates and DRB1*04 as well as DRB1*11 frequencies. The relatively low frequencies of DRB1*04 and high DRB1*11 in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. These specific association patterns suggest that this first study of RA in an Albanian population should be followed up to include second level or higher definition of HLA alleles and to compare RA patterns among European populations.
Published: 2013

50. Evidence on the pathogenic role of auto-antibodies in acute cardiovascular diseases

Author: N. Vuilleumier, François Mach, Fabrizio Montecucco, Alessio Nencioni, and Federico Carbone
Subjects: Myocardial Infarction, Inflammation, Autoimmunity, 030204 cardiovascular system & hematology, medicine.disease_cause, Autoantigens, Epitope, 03 medical and health sciences, 0302 clinical medicine, Immune system, Autoantigens/immunology, Risk Factors, Stroke/blood/immunology, medicine, Animals, Humans, Myocardial infarction, ddc:576, Biological Markers/blood, Receptor, Stroke, Autoantibodies, 030203 arthritis & rheumatology, ddc:616, business.industry, Autoantibody, Hematology, Cardiovascular Diseases/blood/immunology, medicine.disease, Atherosclerosis, Prognosis, Myocardial Infarction/blood/immunology, 3. Good health, Atherosclerosis/blood/immunology, Inflammation/blood/immunology, Cardiovascular Diseases, Immunology, Acute Disease, medicine.symptom, business, Autoantibodies/blood, Biomarkers
Abstract: SummaryAtherothrombosis is the major determinant of acute ischaemic cardiovascular events, such as myocardial infarction and stroke. Inflammatory processes have been linked to all phases of atherogenesis In particular, the identification of autoimmunity mediators in the complex microenvironment of chronic inflammation has become the focus of attention in both early and advanced atherogenic processes. Autoantibodies against self-molecules or new epitopes generated by oxidative processes infiltrate atherosclerotic plaques and were shown to modulate the activity of immune cells by binding various types of receptors. However, despite mounting evidence for a pathophysiological role of autoantibodies in atherothrombosis, the clinical relevance for circulating autoantibodies in cardiovascular outcomes is still debated. This review aims at illustrating the mechanisms by which different types of autoantibodies might either promote or repress atherothrombosis and to discuss the clinical studies assessing the role of auto-antibodies as prognostic biomarkers of plaque vulnerability.
Published: 2012

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