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1. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials.

Author

Siempos, Ilias, Kalil, Andre, Belhadi, Drifa, Veiga, Viviane, Cavalcanti, Alexandre, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta, Kotanidou, Anastasia, Hermine, Olivier, Porcher, Raphaël, and Mariette, Xavier

Subjects
Acute hypoxemic respiratory failure, Acute respiratory distress syndrome, Cancer, Critically ill, Pneumonia
Abstract

BACKGROUND: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. METHODS: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). FINDINGS: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. INTERPRETATION: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. FUNDING: Hellenic Foundation for Research and Innovation.

Published
2024

3. Genome-wide association study identifies Sjögrens risk loci with functional implications in immune and glandular cells.

Author

Khatri, Bhuwan, Tessneer, Kandice, Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara, Baecklund, Eva, Brun, Johan, Bucher, Sara, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart, Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke, Johnsen, Svein, Jonsson, Malin, Kvarnström, Marika, Kelly, Jennifer, Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna, Taylor, Kimberly, Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel, Grundahl, Kiely, Hefner, Kimberly, Radfar, Lida, Lewis, David, Stone, Donald, Kaufman, C, Brennan, Michael, Guthridge, Joel, James, Judith, Scofield, R, Gaffney, Patrick, Criswell, Lindsey, Jonsson, Roland, Eriksson, Per, Bowman, Simon, Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A, Mariette, Xavier, Alarcon-Riquelme, Marta, Shiboski, Caroline, Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy, Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Sjogrens Syndrome
Abstract

Sjögrens disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögrens cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

Published
2022

4. Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance

Author

Ugarte-Gil, Manuel Francisco, Alarcón, Graciela S, Izadi, Zara, Duarte-García, Ali, Reátegui-Sokolova, Cristina, Clarke, Ann Elaine, Wise, Leanna, Pons-Estel, Guillermo J, Santos, Maria Jose, Bernatsky, Sasha, Ribeiro, Sandra Lúcia Euzébio, Al Emadi, Samar, Sparks, Jeffrey A, Hsu, Tiffany Y-T, Patel, Naomi J, Gilbert, Emily L, Valenzuela-Almada, Maria O, Jönsen, Andreas, Landolfi, Gianpiero, Fredi, Micaela, Goulenok, Tiphaine, Devaux, Mathilde, Mariette, Xavier, Queyrel, Viviane, Romão, Vasco C, Sequeira, Graca, Hasseli, Rebecca, Hoyer, Bimba, Voll, Reinhard E, Specker, Christof, Baez, Roberto, Castro-Coello, Vanessa, Ficco, Hernan Maldonado, Neto, Edgard Torres Reis, Ferreira, Gilda Aparecida Aparecida, Monticielo, Odirlei Andre André, Sirotich, Emily, Liew, Jean, Hausmann, Jonathan, Sufka, Paul, Grainger, Rebecca, Bhana, Suleman, Costello, Wendy, Wallace, Zachary S, Jacobsohn, Lindsay, Taylor, Tiffany, Ja, Clairissa, Strangfeld, Anja, Mateus, Elsa F, Hyrich, Kimme L, Carmona, Loreto, Lawson-Tovey, Saskia, Kearsley-Fleet, Lianne, Schäfer, Martin, Machado, Pedro M, Robinson, Philip C, Gianfrancesco, Milena, and Yazdany, Jinoos

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Infectious Diseases, Lupus, Emerging Infectious Diseases, Minority Health, Coronaviruses, Autoimmune Disease, Women's Health, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Inflammatory and immune system, Good Health and Well Being, COVID-19, Humans, Lupus Erythematosus, Systemic, Male, Prednisone, Rheumatology, Severity of Illness Index, lupus erythematosus, systemic, epidemiology, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

AimTo determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19.MethodsPeople with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity.ResultsA total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab.ConclusionsMore severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Published
2022

6. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

Author

Hermine, Olivier, Mariette, Xavier, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Porcher, Raphaël, Pourchet-Martinez, Valerie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Raked, Nabil, Mameri, Lakhdar, Montlahuc, Claire, Biard, Lucie, Alary, St.phanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Charreteur, Robin, Dupre, Céline, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stephan, Nocturne, Gaétane, Bitoun, Samuel, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stephane, Baudry, Elodie, Verny, Christiane, Lefevre, Edouard, Zaidan, Mohamad, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Grimaldi, Lamiae, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Soléne, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Le Tiec, Clotilde, Verstuyft, Céline, Roques, Anne-Marie, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angele, Parrot, Antoine, François, Helene, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadege, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefévre, Guillaume, Gottenberg, Jacques-Eric, Hansmann, Yves, Blanc, Frédéric, Ohlmann-Caillard, Sophie, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurelien, Heger, Bob, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Mertes, Paul-Michel, Noll, Eric, Oberlin, Mathieu, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Weill, François, Meyer, Nicolas, Andres, Emmanuel, Demonsant, Eric, Tayebi, Hakim, Nisand, Gabriel, Brin, Stéphane, Sublon, Cédric, Becker, Guillaume, Hutt, Anne, Martin, Tristan, Bayer, Sophie, Metzger, Catherine, Mekinian, Arsene, Abisror, Noémie, Adedjouma, Amir, Bollens, Diane, Bonneton, Marion, Bourcicaux, Nathalie, Bourrier, Anne, Thibault Chiarabiani, Maria Chauchard, Chopin, Doroth.e, Cohen, Jonathan, Devred, Ines, Donadille, Bruno, Fain, Olivier, Hariri, Geoffrey, Jachiet, Vincent, Ingliz, Patrick, Garnier, Marc, Gatfosse, Marc, Ghrenassia, Etienne, Gobert, Delphine, Krause le Garrec, Jessica, Landman, Cecilia, Lavillegrand, Jean Remy, Lefebvre, Benedicte, Mahevas, Thibault, Mazerand, Sandie, Meynard, Jean Luc, Morgand, Marjolaine, Ouaz.ne, Zineb, Pacanowski, Jerome, Riviere, S.bastien, Seksik, Philippe, Sokol, Harry, Soliman, Heithem, Valin, Nadia, Urbina, Thomas, McAvoy, Chloé, Miranda, Maria Pereira, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Nguyen, Anne Daguenel, Girault, Elise, Mayala-Kanda, Cl.mentine, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Pennet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Denis, Jesuthasan, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Val.rie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Rachline, Anne, Isernia, Valentina, Bao-chau, Phung, Vallois, Dorothée, Sautereau, Aurelie, Neukrich, Catherine, Dossier, Antoine, Borie, Raphaël, Crestani, Bruno, Ducrocq, Gregory, Steg, Philippe Gabriel, Dieude, Philippe, Papo, Thomas, Marcault, Estelle, Chaudhry, Marhaba, Da Silveira, Charléne, Metois, Annabelle, Mahenni, Ismahan, Meziani, Meriam, Nilusmas, Cyndie, Le Gac, Sylvie, Ndiaye, Awa, Louni, Fran.oise, Chansombat, Malikhone, Julia, Zelie, Chalal, Solaya, Chalal, Lynda, Kramer, Laura, Le Grand, Jeniffer, Ouifiya, Kafif, Piquard, Valentine, Tubiana, Sarah, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anais, Zarrouk, Virginie, de Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Claveirole, Agathe, Navid, Alexandre, Fouque, Tiffanie, Cohen, Yonathan, Lupo, Maya, Gilles, Constance, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, de Castro, Nathalie, Clément, Melissa, Darmon, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lenglin, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asma, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Lebras, Karine Celli, Chabert, Julien, Djaghout, Lamia, Fauvaux, Catherine, Jegu, Anne Lise, Kozakiewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madelaine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sène, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Mégarbanne, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vazquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Tran, Olivia, Jouis, Véronique, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sébastien, nainous, Ruben B., Bonnet, Nicolas, Comparon, Celine, Cohen, Yves, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Gille, Thomas, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Nunes, Hilario, Oziel, Johanna, Roulot, Dominique, Sese, Lucile, ClaireTantet, Uzunhan, Yurdagul, Bloch-Queyrat, Coralie, Levy, Vincent, Messani, Fadhila, Rahaoui, Mohammed, Petit, Myléne, Brahmi, Sabrina, Rathoin, Vanessa, Rigal, Marthe, Costedoat-Chalumeau, Nathalie, Luong, Liem Binh, Hamou, Zakaria Ait, Benghanem, Sarah, Blanche, Philippe, Carlier, Nicolas, Chaigne, Benjamin, Gauzit, Remy, Joumaa, Hassan, Jozwiak, Mathieu, Lachétre, Marie, Lafoeste, Hélène, Launay, Odie, Legendre, Paul, Marey, Jonathan, Morbieu, Caroline, Palmieri, Lola-Jade, Szwebel, Tali-Anne, Abdoul, Hendy, Bruneau, Alexandra, Beclin-Clabaux, Audrey, Larrieu, Charly, Montanari, Pierre, Dufour, Eric, Clarke, Ada, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Saleh-Mghir, Samira, Cisse, Mamadou Salif, Cheref, Kahina, Guerin, Corinne, Zerbit, Jérémie, Michel, Marc, Gallien, Sébastien, Crickx, Etienne, Le Vavasseur, Benjamin, Kempf, Emmanuelle, Jaffal, Karim, Vindrios, William, Oniszczuk, Julie, Guillaud, Constance, Lim, Pascal, Fois, Elena, Melica, Giovanna, Matignon, Marie, Jalabert, Maud, Lelièvre, Jean-Daniel, Schmitz, David, Bourhis, Marion, Belazouz, Sylia, Languille, Laetitia, Boucle, Caroline, Cita, Nelly, Didier, Agnés, Froura, Fahem, Ledudal, Katia, Sadaoui, Thiziri, Thiemele, Alaki, Le Febvre De Bailly, Delphine, Verlinde, Muriel Carvhalo, Mayaux, Julien, Cacoub, Patrice, Saadoun, David, Vautier, Mathieu, Bugaut, Héléne, Benveniste, Olivier, Allenbach, Yves, Leroux, Gaëlle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Chloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Goncalo, Ferfar, Yasmina, Corvol, Jean-Christophe, Louapre, C.line, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aicha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sebastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Fournier, Benjamin, Rouzaud, Claire, Vimpére, Damien, Elie, Caroline, Bakouboula, Prissile, Choupeaux, Laure, Granville, Sophie, Issorat, Elodie, Broissand, Christine, Alyanakian, Marie-Alexandra, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Héléne, Duclos-vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Kounis, Ilias, Tamazirt, Sonia, Rudant, Eric, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Christophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Netzer, Florence, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Héléne, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Chan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Marquis, Eric, Benoit, Philippe, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Helene, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, Ader, F., Yazdanpanah, Y., Mentre, F., Peiffer-Smadja, N., Lescure, F.X., Poissy, J., Bouadma, L., Timsit, J.F., Lina, B., Morfin-Sherpa, F., Bouscambert, M., Gaymard, A., Peytavin, G., Abel, L., Guedj, J., Andrejak, C., Burdet, C., Laouenan, C., Belhadi, D., Dupont, A., Alfaiate, T., Basli, B., Chair, A., Laribi, S., Level, J., Schneider, M., Tellier, M.C., Dechanet, A., Costagliola, D., Terrier, B., Ohana, M., Couffin-Cadiergues, S., Esperou, H., Delmas, C., Saillard, J., Fougerou, C., Moinot, L., Wittkop, L., Cagnot, C., Le Mestre, S., Lebrasseur-Longuet, D., Petrov-Sanchez, V., Diallo, A., Mercier, N., Icard, V., Leveau, B., Tubiana, S., Hamze, B., Gelley, A., Noret, M., D’Ortenzio, E., Puechal, O., Semaille, C., Welte, T., Paiva, J.A., Halanova, M., Kieny, M.P., Balssa, E., Birkle, C., Gibowski, S., Landry, E., Le Goff, A., Moachon, L., Moins, C., Wadouachi, L., Paul, C., Levier, A., Bougon, D., Djossou, F., Epelboin, L., Dellamonica, J., Marquette, C.H., Robert, C., Gibot, S., Senneville, E., Jean-Michel, V., Zerbib, Y., Chirouze, C., Boyer, A., Cazanave, C., Gruson, D., Malvy, D., Andreu, P., Quenot, J.P., Terzi, N., Faure, K., Chabartier, C., Le Moing, V., Klouche, K., Ferry, T., F, Valour, Gaborit, B., Canet, E., Le Turnier, P., Boutoille, D., Bani-Sadr, F., Benezit, F., Revest, M., Cameli, C., Caro, A., Um Tegue, MJ Ngo, Le Tulzo, Y., Laviolle, B., Laine, F., Thiery, G., Meziani, F., Hansmann, Y., Oulehri, W., Tacquard, C., Vardon-Bounes, F., Riu-Poulenc, B., Murris-Espin, M., Bernard, L., Garot, D., Hinschberger, O., Martinot, M., Bruel, C., Pilmis, B., Bouchaud, O., Loubet, P., Roger, C., Monnet, X., Figueiredo, S., Godard, V., Mira, J.P., Lachatre, M., Kerneis, S., Aboab, J., Sayre, N., Crockett, F., Lebeaux, D., Buffet, A., Diehl, J.L., Fayol, A., Hulot, J.S., Livrozet, M., Dessap, A Mekontso, Ficko, C., Stefan, F., Le Pavec, J., Mayaux, J., Ait-Oufella, H., Molina, J.M., Pialoux, G., Fartoukh, M., Textoris, J., Brossard, M., Essat, A., Netzer, E., Riault, Y., Ghislain, M., Beniguel, L., Genin, M., Gouichiche, L., Betard, C., Belkhir, L., Altdorfer, A., Centro, V Fraipont, Braz, S., Ribeiro, JM Ferreira, Alburqueque, R Roncon, Berna, M., Alexandre, M., Lamprecht, B., Egle, A., Greil, R., Joannidis, M., Patterson, Thomas F., Ponce, Philip O., Taylor, Barbara S., Patterson, Jan E., Bowling, Jason E., Javeri, Heta, Kalil, Andre C., Larson, LuAnn, Hewlett, Angela, Mehta, Aneesh K., Rouphael, Nadine G., Saklawi, Youssef, Scanlon, Nicholas, Traenkner, Jessica J., Trible, Ronald P., Jr., Walter, Emmanuel B., Ivey, Noel, Holland, Thomas L., Ruiz-Palacios, Guillermo M., Ponce de León, Alfredo, Rajme, Sandra, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Lee, Helen S., Kline, Susan, Billings, Joanne, Noren, Brooke, Kim, Hyun, Bold, Tyler D., Tapson, Victor, Grein, Jonathan, Sutterwala, Fayyaz, Iovine, Nicole, Beattie, Lars K., Wakeman, Rebecca Murray, Shaw, Matthew, Jain, Mamta K., Mocherla, Satish, Meisner, Jessica, Luque, Amneris, Sweeney, Daniel A., Benson, Constance A., Ali, Farhana, Atmar, Robert L., El Sahly, Hana M., Whitaker, Jennifer, Falsey, Ann R., Branche, Angela R., Rozario, Cheryl, Pineda, Justino Regalado, Martinez-Orozco, José Arturo, Lye, David Chien, Ong, Sean WX., Chia, Po Ying, Young, Barnaby E., Sandkovsky, Uriel, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Cantos, Valeria D., Kelley, Colleen F., Rebolledo Esteinou, Paulina A., Kandiah, Sheetal, Doernberg, Sarah B., Crouch, Pierre-Cedric B., Jang, Hannah, Luetkemeyer, Anne F., Dwyer, Jay, Cohen, Stuart H., Thompson, George R., 3rd, Nguyen, Hien H., Finberg, Robert W., Wang, Jennifer P., Perez-Velazquez, Juan, Wessolossky, Mireya, Jackson, Patrick E.H., Bell, Taison D., West, Miranda J., Taiwo, Babafemi, Krueger, Karen, Perez, Johnny, Pearson, Triniece, Paules, Catharine I., Julian, Kathleen G., Ahmad, Danish, Hajduczok, Alexander G., Arguinchona, Henry, Arguinchona, Christa, Erdmann, Nathaniel, Goepfert, Paul, Ahuja, Neera, Frank, Maria G., Wyles, David, Young, Heather, Oh, Myoung-don, Park, Wan Beom, Kang, Chang Kyung, Marconi, Vincent, Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Kim, Eu Suk, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Tan, Seow Yen, Shafi, Humaira, Chien, Jaime, Fong, Raymond KC., Murray, Daniel D., Lundgren, Jens, Nielsen, Henrik, Jensen, Tomas, Zingman, Barry S., Grossberg, Robert, Riska, Paul F., Yang, Otto O., Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R., Hauser, Naomi, Campbell, James D., Short, William R., Tebas, Pablo, Baron, Jillian T., McLellan, Susan L.F., Blanton, Lucas S., Seashore, Justin B., Creech, C. Buddy, Rice, Todd W., Walker, Shannon, Thomsen, Isaac P., Lopez de Castilla, Diego, Van Winkle, Jason W., Riedo, Francis X., Pada, Surinder Kaur, Wang, Alvin DY., Lin, Li, Harkins, Michelle, Mertz, Gregory, Sosa, Nestor, Ann Chai, Louis Yi, Tambyah, Paul Anantharajah, Tham, Sai Meng, Archuleta, Sophia, Yan, Gabriel, Lindholm, David A., Markelz, Ana Elizabeth, Mende, Katrin, Mularski, Richard, Hohmann, Elizabeth, Torres-Soto, Mariam, Jilg, Nikolaus, Maves, Ryan C., Utz, Gregory C., George, Sarah L., Hoft, Daniel F., Brien, James D., Paredes, Roger, Mateu, Lourdes, Loste, Cora, Kumar, Princy, Thornton, Sarah, Mohanraj, Sharmila, Hynes, Noreen A., Sauer, Lauren M., Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Chambers, Susan E., Novak, Richard M., Wendrow, Andrea, Gupta, Samir K., Lee, Tida, Lalani, Tahaniyat, Holodniy, Mark, Chary, Aarthi, Huprikar, Nikhil, Ganesan, Anuradha, Ohmagari, Norio, Mikami, Ayako, Price, D. Ashley, Duncan, Christopher J.A., Dierberg, Kerry, Neumann, Henry J., Taylor, Stephanie N., Lacour, Alisha, Masri, Najy, Swiatlo, Edwin, Widmer, Kyle, Neaton, James D., Bessesen, Mary, Stephens, David S., Burgess, Timothy H., Uyeki, Timothy M., Walker, Robert, Marks, G. Lynn, Osinusi, Anu, Cao, Huyen, Cardoso, Anabela, de Bono, Stephanie, Schlichting, Douglas E., Chung, Kevin K., Ferreira, Jennifer L., Green, Michelle, Makowski, Mat, Wierzbicki, Michael R., Conrad, Tom M., El-Khorazaty, Jill Ann, Hill, Heather, Bonnett, Tyler, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Beigel, John H., Tomashek, Kay M., Ghazaryan, Varduhi, Beresnev, Tatiana, Nayak, Seema, Dodd, Lori E., Dempsey, Walla, Nomicos, Effie, Lee, Marina, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Voell, Jocelyn D., Davey, Richard, Serrano, Ruth C., Wiley, Zanthia, Phadke, Varun K., Goepfert, Paul A., Gomez, Carlos A., Sofarelli, Theresa A., Certain, Laura, Imlay, Hannah N., Wolfe, Cameron R., Ko, Emily R., Engemann, John J., Felix, Nora Bautista, Wan, Claire R., Elmor, Sammy T., Bristow, Laurel R., Harkins, Michelle S., Iovine, Nicole M., Elie-Turenne, Marie-Carmelle, Tapson, Victor F., Choe, Pyoeng Gyun, Mularski, Richard A., Rhie, Kevin S., Hussein, Rezhan H., Ince, Dilek, Winokur, Patricia L., Takasaki, Jin, Saito, Sho, McConnell, Kimberly, Wyles, David L., Sarcone, Ellen, Grimes, Kevin A., Perez, Katherine, Janak, Charles, Whitaker, Jennifer A., Rebolledo, Paulina A., Gharbin, John, Lambert, Allison A., Zea, Diego F., Bainbridge, Emma, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Ling, Evelyn, Go, Minjoung, Hubbard, Fleesie A., Chakrabarty, Melony, Laguio-Vila, Maryrose, Walsh, Edward E., Guirgis, Faheem, Marconi, Vincent C., Madar, Christian, Borgetti, Scott A., Levine, Corri, Nock, Joy, Candiotti, Keith, Rozman, Julia, Dangond, Fernando, Hyvert, Yann, Seitzinger, Andrea, Cross, Kaitlyn, Pettibone, Stephanie, Nayak, Seema U., Deye, Gregory A., Siempos, Ilias I., Belhadi, Drifa, Veiga, Viviane Cordeiro, Cavalcanti, Alexandre Biasi, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta A., and Kotanidou, Anastasia

Published
2024
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7. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2023
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9. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus

Author

Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey‐Goldman, Rosalind, Smolen, Josef S, Wofsy, David, Boumpas, Dimitrios T, Kamen, Diane L, Jayne, David, Cervera, Ricard, Costedoat‐Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D, Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz‐Irastorza, Guillermo, Sanchez‐Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F, Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K, Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K, Czirják, László, Doria, Andrea, Graninger, Winfried, Halda‐Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M, Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego‐Reigosa, José M, Romero‐Diaz, Juanita, Fernández, Íñigo Rúa‐Figueroa, Seror, Raphaèle, Stummvoll, Georg H, Tanaka, Yoshiya, Tektonidou, Maria G, Vasconcelos, Carlos, Vital, Edward M, Wallace, Daniel J, Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J, Naden, Ray, Dörner, Thomas, and Johnson, Sindhu R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lupus, Autoimmune Disease, Inflammatory and immune system, Adult, Antibodies, Antinuclear, Antibodies, Antiphospholipid, Autoantibodies, Cohort Studies, Complement System Proteins, Decision Support Techniques, Delphi Technique, Europe, Female, Humans, International Cooperation, Lupus Erythematosus, Systemic, Male, Middle Aged, Rheumatology, Sensitivity and Specificity, Societies, Medical, United States, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveTo develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).MethodsThis international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.ResultsThe 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.ConclusionThese new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.

Published
2019

10. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

Author

Hermine, Olivier, Mariette, Xavier, Porcher, Raphael, Djossou, Felix, Nguyen, Yann, Arlet, Jean-Benoît, Savale, Laurent, Diehl, Jean Luc, Georgin-Lavialle, Sophie, Cadranel, Jacques, Pialoux, Gilles, Lacombe, Karine, Mekinian, Arsène, Gros, Hélène, Lescure, Xavier, Ghosn, Jade, Coupez, Elisabeth, Grapin, Kevin, Rapp, Christophe, Michel, Marc, Lecapitaine, Anne Lise, Michot, Jean Marie, Costedoat-Chalumeau, Nathalie, Nguyen, Liem Binh Luong, Semerano, Luca, Raffi, François, Aguillar, Claire, Rouzaud, Claire, Gottenberg, Jacques Eric, Hansmann, Yves, Bienvenu, Boris, London, Jonathan, Fantchou, Franklin Samou, Ackermann, Felix, Gros, Antoine, Morel, Alexandre, Gambier, Nicolas, Sène, Damien, Mégarbane, Bruno, Azoulay, Elie, Bureau, Serge, Dougados, Maxime, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Mahevas, Mathieu, Pène, Frédéric, Schlemmer, Frédéric, Pourcher-Martinez, Valérie, Tibi, Annick, Baron, Gabriel, Perrodeau, Elodie, Baron, Stéphanie, Steg, Gabriel, Yazdapanah, Yazdan, Simon, Tabassome, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, and Ravaud, Philippe

Published
2022
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12. Addressing the clinical unmet needs in primary Sjögren’s Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

Author

Vasileios C. Pezoulas, Andreas Goules, Fanis Kalatzis, Luke Chatzis, Konstantina D. Kourou, Aliki Venetsanopoulou, Themis P. Exarchos, Saviana Gandolfo, Konstantinos Votis, Evi Zampeli, Jan Burmeister, Thorsten May, Manuel Marcelino Pérez, Iryna Lishchuk, Thymios Chondrogiannis, Vassiliki Andronikou, Theodora Varvarigou, Nenad Filipovic, Manolis Tsiknakis, Chiara Baldini, Michele Bombardieri, Hendrika Bootsma, Simon J. Bowman, Muhammad Shahnawaz Soyfoo, Dorian Parisis, Christine Delporte, Valérie Devauchelle-Pensec, Jacques-Olivier Pers, Thomas Dörner, Elena Bartoloni, Roberto Gerli, Roberto Giacomelli, Roland Jonsson, Wan-Fai Ng, Roberta Priori, Manuel Ramos-Casals, Kathy Sivils, Fotini Skopouli, Witte Torsten, Joel A. G. van Roon, Mariette Xavier, Salvatore De Vita, Athanasios G. Tzioufas, and Dimitrios I. Fotiadis

Subjects
Data sharing, Data curation, Data harmonization, Federated AI, Lymphoma classification, Biomarkers, Biotechnology, TP248.13-248.65
Abstract

For many decades, the clinical unmet needs of primary Sjögren’s Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs.

Published
2022
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13. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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14. 2016 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Primary Sjögren's Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts.

Author

Shiboski, Caroline H, Shiboski, Stephen C, Seror, Raphaèle, Criswell, Lindsey A, Labetoulle, Marc, Lietman, Thomas M, Rasmussen, Astrid, Scofield, Hal, Vitali, Claudio, Bowman, Simon J, Mariette, Xavier, and International Sjögren's Syndrome Criteria Working Group

Subjects
International Sjögren's Syndrome Criteria Working Group, Humans, Sjogren's Syndrome, Internationality, United States, Practice Guidelines as Topic, Datasets as Topic, Clinical Research, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

ObjectiveTo develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.MethodsWe assigned preliminary importance weights to a consensus list of candidate criteria items, using multi-criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non-SS controls, with case/non-case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients.ResultsThe final classification criteria are based on the weighted sum of 5 items: anti-SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2 , each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician-expert-derived case/non-case status in the final validation cohort were high, i.e., 96% (95% confidence interval [95% CI] 92-98%) and 95% (95% CI 92-97%), respectively.ConclusionUsing methodology consistent with other recent ACR/EULAR-approved classification criteria, we developed a single set of data-driven consensus classification criteria for primary SS, which performed well in validation analyses and are well-suited as criteria for enrollment in clinical trials.

Published
2017

15. Consensus gene modules strategy identifies candidate blood-based biomarkers for primary Sjögren's disease

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, Becht, Etienne, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, MS Reumatologie/Immunologie/Infectie, Boudjeniba, Cheïma, Soret, Perrine, Trutschel, Diana, Hamon, Antoine, Baloche, Valentin, Chassagnol, Bastien, Desvaux, Emiko, Bichat, Antoine, Aussy, Audrey, Moingeon, Philippe, Lefebvre, Céline, Hubert, Sandra, Alarcon-Riquelmé, Marta, Ng, Wan Fai, Gottenberg, Jacques Eric, Schwikowski, Benno, Bombardieri, Michele, van Roon, Joel A.G., Mariette, Xavier, Guedj, Mickaël, Birmele, Etienne, Laigle, Laurence, and Becht, Etienne

Published
2024

16. The Sjögren's Working Group:The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., Seror, Raphaele, Gordon, Rachael A., Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A., Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan Fai, Mendonça, Jose Alexandre, Wallace, Daniel J., Shea, Beverley, Bruyn, George AW, Goodman, Susan M., Fisher, Benjamin A., Baldini, Chiara, Torralba, Karina D., Bootsma, Hendrika, Akpek, Esen K., Karakus, Sezen, Baer, Alan N., Chakravarty, Soumya D., Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, DiRenzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M., Hammitt, Katherine M., Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Luis, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H., Benyoussef, Anas, Masli, Sharmila, Lee, Adrian Y.S., Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, McCoy, Sara S., and Seror, Raphaele

Abstract

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity, Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

Published
2024

17. Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept:Results from the international TOCERRA and PANABA observational collaborative studies

Author

Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, Gabay, Cem, Lauper, Kim, Mongin, Denis, Bergstra, Sytske Anne, Choquette, Denis, Codreanu, Catalin, Gottenberg, Jacques Eric, Kubo, Satoshi, Hetland, Merete Lund, Iannone, Florenzo, Kristianslund, Eirik K., Kvien, Tore K., Lukina, Galina, Mariette, Xavier, Nordström, Dan C., Pavelka, Karel, Pombo-Suarez, Manuel, Rotar, Ziga, Santos, Maria J., Tanaka, Yoshiya, Turesson, Carl, Courvoisier, Delphine S., Finckh, Axel, and Gabay, Cem

Abstract

Objective To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved., Objective: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

Published
2024

18. The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation

Author

Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060), Gordon, Rachael A, Nguyen, Yann, Foulquier, Nathan, Beydon, Maxime, Gheita, Tamer A, Hajji, Raouf, Sahbudin, Ilfita, Hoi, Alberta, Ng, Wan-Fai, Mendonça, Jose Alexandre, Wallace, Daniel J, Shea, Beverley, Bruyn, George Aw, Goodman, Susan M, Fisher, Benjamin A, Baldini, Chiara, Torralba, Karina D, Bootsma, Hendrika, Akpek, Esen K, Karakus, Sezen, Baer, Alan N, Chakravarty, Soumya D, Terslev, Lene, D'Agostino, Maria Antonietta, Mariette, Xavier, Direnzo, Dana, Rasmussen, Astrid, Papas, Athena, Montoya, Cristina, Arends, Suzanne, Yusof, Md Yuzaiful Md, Pintilie, Ionut, Warner, Blake M, Hammitt, Katherine M, Strand, Vibeke, Bouillot, Coralie, Tugwell, Peter, Inanc, Nevsun, Andreu, José Lui, Wahren-Herlenius, Marie, Devauchelle-Pensec, Valerie, Shiboski, Caroline H, Benyoussef, Ana, Masli, Sharmila, Lee, Adrian Y S, Cornec, Divi, Bowman, Simon, Rischmueller, Maureen, Mccoy, Sara S, Seror, Raphaele, and D'Agostino, Maria-Antonietta (ORCID:0000-0002-5347-0060)

Abstract

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.

Published
2024

22. Characterisation of airway disease associated with Sjögren disease

Author

Meudec, Loïc, primary, Debray, Marie-Pierre, additional, Beurnier, Antoine, additional, Marques, Cindy, additional, Juge, Pierre-Antoine, additional, Dhote, Robin, additional, Larroche, Claire, additional, Fauchais, Anne Laure, additional, Dernis, Emanuelle, additional, Vittecoq, Olivier, additional, Saraux, Alain, additional, Gottenberg, Jacques-Eric, additional, Hachulla, Eric, additional, Le Guern, Véronique, additional, Dieudé, Philippe, additional, Seror, Raphaele, additional, Mariette, Xavier, additional, and Nocturne, Gaétane, additional

Published
2024
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23. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Author

Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Scofield, R Hal, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Sivils, Kathy L Moser, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, and Kaufman, Kenneth M

Subjects
Biological Sciences, Genetics, Autoimmune Disease, Biotechnology, Lupus, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Autoimmune Diseases, Bayes Theorem, Case-Control Studies, Cohort Studies, DNA-Binding Proteins, Haplotypes, Humans, Interferon Regulatory Factors, Lupus Erythematosus, Systemic, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, beta Karyopherins, UK Primary Sjögren's Syndrome Registry, Medical and Health Sciences, Genetics & Heredity
Abstract

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

Published
2015

26. Genetics of rheumatoid arthritis contributes to biology and drug discovery.

Author

Okada, Yukinori, Wu, Di, Trynka, Gosia, Raj, Towfique, Terao, Chikashi, Ikari, Katsunori, Kochi, Yuta, Ohmura, Koichiro, Suzuki, Akari, Yoshida, Shinji, Graham, Robert, Manoharan, Arun, Ortmann, Ward, Bhangale, Tushar, Denny, Joshua, Carroll, Robert, Eyler, Anne, Greenberg, Jeffrey, Kremer, Joel, Pappas, Dimitrios, Jiang, Lei, Yin, Jian, Ye, Lingying, Su, Ding-Feng, Yang, Jian, Xie, Gang, Keystone, Ed, Westra, Harm-Jan, Esko, Tõnu, Metspalu, Andres, Zhou, Xuezhong, Gupta, Namrata, Mirel, Daniel, Stahl, Eli, Diogo, Dorothée, Cui, Jing, Liao, Katherine, Guo, Michael, Myouzen, Keiko, Kawaguchi, Takahisa, Coenen, Marieke, van Riel, Piet, van de Laar, Mart, Guchelaar, Henk-Jan, Huizinga, Tom, Dieudé, Philippe, Mariette, Xavier, Bridges, S, Zhernakova, Alexandra, Toes, Rene, Tak, Paul, Miceli-Richard, Corinne, Bang, So-Young, Lee, Hye-Soon, Martin, Javier, Gonzalez-Gay, Miguel, Rodriguez-Rodriguez, Luis, Rantapää-Dahlqvist, Solbritt, Arlestig, Lisbeth, Choi, Hyon, Kamatani, Yoichiro, Galan, Pilar, Lathrop, Mark, Eyre, Steve, Bowes, John, Barton, Anne, de Vries, Niek, Moreland, Larry, Karlson, Elizabeth, Taniguchi, Atsuo, Yamada, Ryo, Kubo, Michiaki, Liu, Jun, Bae, Sang-Cheol, Worthington, Jane, Padyukov, Leonid, Klareskog, Lars, Gregersen, Peter, Raychaudhuri, Soumya, Stranger, Barbara, De Jager, Philip, Franke, Lude, Visscher, Peter, Brown, Matthew, Yamanaka, Hisashi, Mimori, Tsuneyo, Takahashi, Atsushi, Xu, Huji, Behrens, Timothy, Siminovitch, Katherine, Momohara, Shigeki, Matsuda, Fumihiko, Yamamoto, Kazuhiko, Plenge, Robert, and Criswell, Lindsey

Subjects
Alleles, Animals, Arthritis, Rheumatoid, Asian People, Case-Control Studies, Computational Biology, Drug Discovery, Drug Repositioning, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hematologic Neoplasms, Humans, Male, Mice, Mice, Knockout, Molecular Targeted Therapy, Polymorphism, Single Nucleotide, White People
Abstract

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

Published
2014

27. Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature.

Author

Kachaner, Alexandra, Seror, Raphaèle, Aubart, Fleur Cohen, Henry, Julien, Lazure, Thierry, Emile, Jean François, Mariette, Xavier, and Bitoun, Samuel

Subjects
LANGERHANS-cell histiocytosis, LITERATURE reviews, BONE cells, POSITRON emission tomography computed tomography, THERAPEUTICS
Abstract

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Liposomal AntagomiR‐155‐5p Restores Anti‐Inflammatory Macrophages and Improves Arthritis in Preclinical Models of Rheumatoid Arthritis

Author

Paoletti, Audrey, primary, Ly, Bineta, additional, Cailleau, Catherine, additional, Gao, Fan, additional, de Ponfilly‐Sotier, Marie Péan, additional, Pascaud, Juliette, additional, Rivière, Elodie, additional, Yang, Luxin, additional, Nwosu, Lilian, additional, Elmesmari, Aziza, additional, Reynaud, Franceline, additional, Hita, Magali, additional, Paterson, David, additional, Reboud, Julien, additional, Fay, Francois, additional, Nocturne, Gaetane, additional, Tsapis, Nicolas, additional, McInnes, Iain B., additional, Kurowska‐Stolarska, Mariola, additional, Fattal, Elias, additional, and Mariette, Xavier, additional

Published
2023
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29. More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients

Author

Joly, Candie, primary, Desjardins, Delphine, additional, Porcher, Raphael, additional, Péré, Hélène, additional, Bruneau, Thomas, additional, Zhang, Qian, additional, Bastard, Paul, additional, Cobat, Aurélie, additional, Resmini, Léa, additional, Lenoir, Olivia, additional, Savale, Laurent, additional, Lécuroux, Camille, additional, Verstuyft, Céline, additional, Roque-Afonso, Anne-Marie, additional, Veyer, David, additional, Baron, Gabriel, additional, Resche-Rigon, Matthieu, additional, Ravaud, Philippe, additional, Casanova, Jean-Laurent, additional, Le Grand, Roger, additional, Hermine, Olivier, additional, Tharaux, Pierre-Louis, additional, and Mariette, Xavier, additional

Published
2023
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30. The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection

Author

Lécuyer, Déborah, primary, Nardacci, Roberta, additional, Tannous, Désirée, additional, Gutierrez-Mateyron, Emie, additional, Deva Nathan, Aurélia, additional, Subra, Frédéric, additional, Di Primio, Cristina, additional, Quaranta, Paola, additional, Petit, Vanessa, additional, Richetta, Clémence, additional, Mostefa-Kara, Ali, additional, Del Nonno, Franca, additional, Falasca, Laura, additional, Marlin, Romain, additional, Maisonnasse, Pauline, additional, Delahousse, Julia, additional, Pascaud, Juliette, additional, Deprez, Eric, additional, Naigeon, Marie, additional, Chaput, Nathalie, additional, Paci, Angelo, additional, Saada, Véronique, additional, Ghez, David, additional, Mariette, Xavier, additional, Costa, Mario, additional, Pistello, Mauro, additional, Allouch, Awatef, additional, Delelis, Olivier, additional, Piacentini, Mauro, additional, Le Grand, Roger, additional, and Perfettini, Jean-Luc, additional

Published
2023
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32. Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial

Author

Lacombe, Karine, primary, Hueso, Thomas, additional, Porcher, Raphael, additional, Mekinian, Arsene, additional, Chiarabini, Thibault, additional, Georgin-Lavialle, Sophie, additional, Ader, Florence, additional, Saison, Julien, additional, Martin-Blondel, Guillaume, additional, De Castro, Nathalie, additional, Bonnet, Fabrice, additional, Cazanave, Charles, additional, Francois, Anne, additional, Morel, Pascal, additional, Hermine, Olivier, additional, Pourcher, Valerie, additional, Michel, Marc, additional, Lescure, Xavier, additional, Soussi, Nora, additional, Brun, Phillipe, additional, Pommeret, Fanny, additional, Sellier, Pierre, additional, Rousset, Stella, additional, Piroth, Lionel, additional, Michot, Jean-Marie, additional, Baron, Gabriel, additional, de Lamballerie, Xavier, additional, Mariette, Xavier, additional, Tharaux, Pierre-Louis, additional, Resche-Rigon, Matthieu, additional, Ravaud, Philippe, additional, Simon, Tabassome, additional, and Tiberghien, Pierre, additional

Published
2023
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33. Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis

Author

Mirkov, Maša Umiċeviċ, Cui, Jing, Vermeulen, Sita H, Stahl, Eli A, Toonen, Erik JM, Makkinje, Remco R, Lee, Annette T, Huizinga, Tom WJ, Allaart, Renee, Barton, Anne, Mariette, Xavier, Miceli, Corinne Richard, Criswell, Lindsey A, Tak, Paul P, de Vries, Niek, Saevarsdottir, Saedis, Padyukov, Leonid, Bridges, S Louis, van Schaardenburg, Dirk-Jan, Jansen, Tim L, Dutmer, Ellen AJ, van de Laar, Mart AFJ, Barrera, Pilar, Radstake, Timothy RDJ, van Riel, Piet LCM, Scheffer, Hans, Franke, Barbara, Brunner, Han G, Plenge, Robert M, Gregersen, Peter K, Guchelaar, Henk-Jan, and Coenen, Marieke JH

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Arthritis, Rheumatoid Arthritis, Genetics, Autoimmune Disease, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adalimumab, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antirheumatic Agents, Arthritis, Rheumatoid, DNA Mutational Analysis, Drug Resistance, Etanercept, Female, Gene Expression Regulation, Genetic Markers, Genome-Wide Association Study, Humans, Immunoglobulin G, Infliximab, Male, Polymorphism, Single Nucleotide, Receptors, Tumor Necrosis Factor, Registries, Tumor Necrosis Factor-alpha, Anti-TNF, Gene Polymorphism, Pharmacogenetics, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

BackgroundTreatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach.MethodsWe conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p

Published
2013

34. NCR3/NKp30 Contributes to Pathogenesis in Primary Sjögren’s Syndrome

Author

Rusakiewicz, Sylvie, Nocturne, Gaetane, Lazure, Thierry, Semeraro, Michaela, Flament, Caroline, Caillat-Zucman, Sophie, Sène, Damien, Delahaye, Nicolas, Vivier, Eric, Chaba, Kariman, Poirier-Colame, Vichnou, Nordmark, Gunnel, Eloranta, Maija-Leena, Eriksson, Per, Theander, Elke, Forsblad-d’Elia, Helena, Omdal, Roald, Wahren-Herlenius, Marie, Jonsson, Roland, Rönnblom, Lars, Nititham, Joanne, Taylor, Kimberly E, Lessard, Christopher J, Sivils, Kathy L Moser, Gottenberg, Jacques-Eric, Criswell, Lindsey A, Miceli-Richard, Corinne, Zitvogel, Laurence, and Mariette, Xavier

Subjects
Autoimmune Disease, Rare Diseases, Genetics, Clinical Research, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adult, Aged, Cell Line, Cells, Cultured, Female, Genotype, Humans, Interferon-gamma, Male, Middle Aged, Natural Cytotoxicity Triggering Receptor 3, Polymorphism, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Sjogren's Syndrome, Biological Sciences, Medical and Health Sciences
Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.

Published
2013

35. Can efficacy and safety data from clinical trials of rituximab in RA be extrapolated? Insights from 1984 patients from the AIR-PR Registry

Author

Nguyen, Yann, primary, Mariette, Xavier, additional, Gottenberg, Jacques E, additional, Iudici, Michele, additional, Morel, Jacques, additional, Vittecoq, Olivier, additional, Constantin, Arnaud, additional, Flipo, Rene-Marc, additional, Schaeverbeke, Thierry, additional, Sibilia, Jean, additional, Ravaud, Philippe, additional, Porcher, Raphaël, additional, and Seror, Raphaèle, additional

Published
2023
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36. Efficacy of daratumumab in refractory primary Sjögren disease

Author

Nocturne, Gaetane, primary, Marmontel, Oriane, additional, di Filippo, Mathilde, additional, Chretien, Pascale, additional, Krzysiek, Roman, additional, Lifermann, Francois, additional, Rahal, Nawal, additional, Belkhir, Rakiba, additional, Moulin, Philippe, additional, and Mariette, Xavier, additional

Published
2023
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40. Bruton's tyrosine kinase (BTK) gene overexpression is associated with risk of lymphoma in primary Sjögren's syndrome

Author

Duret, Pierre‐Marie, primary, Schleiss, Cedric, additional, Kawka, Lou, additional, Meyer, Nicolas, additional, Ye, Tao, additional, Saraux, Alain, additional, Devauchelle‐Pensec, Valérie, additional, Seror, Raphaele, additional, Larroche, Claire, additional, Perdriger, Aleth, additional, Sibilia, Jean, additional, Vallat, Laurent, additional, Fornecker, Luc‐Matthieu, additional, Nocturne, Gaetane, additional, Mariette, Xavier, additional, and Gottenberg, Jacques‐Eric, additional

Published
2023
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41. P111 Exploratory Analysis of Filgotinib Safety Data in Patients With Moderately to Severely Active Rheumatoid arthritis and an Increased Risk of Cardiovascular Events: Data From Phase 2 and 3 Clinical Trials

Author

Buch, Maya H, primary, Burmester, Gerd R, additional, Mariette, Xavier, additional, Charles-Schoeman, Christina, additional, Rajendran, Vijay, additional, Stiers, Pieter-Jan, additional, Cerani, Agustin, additional, Van Hoek, Paul, additional, Van Beneden, Katrien, additional, Tanaka, Yoshiya, additional, Schulze-Koops, Hendrik, additional, Westhovens, René, additional, and Favalli, Ennio, additional

Published
2023
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42. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Author

MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, Smolen, Josef S., MS Reumatologie/Immunologie/Infectie, Infection & Immunity, Aletaha, Daniel, Kerschbaumer, Andreas, Kastrati, Kastriot, Dejaco, Christian, Dougados, Maxime, McInnes, Iain B., Sattar, Naveed, Stamm, Tanja A., Takeuchi, Tsutomu, Trauner, Michael, Van Der Heijde, Désirée, Voshaar, Marieke, Winthrop, Kevin L., Ravelli, Angelo, Betteridge, Neil, Burmester, Gerd Rüdiger R., Bijlsma, Johannes W.J., Bykerk, Vivian, Caporali, Roberto, Choy, Ernest H., Codreanu, Catalin, Combe, Bernard, Crow, Mary K., De Wit, Maarten, Emery, Paul, Fleischmann, Roy M., Gabay, Cem, Hetland, Merete Lund, Hyrich, Kimme L., Iagnocco, Annamaria, Isaacs, John D., Kremer, Joel M., Mariette, Xavier, Merkel, Peter A., Mysler, Eduardo F., Nash, Peter, Nurmohamed, Michael T., Pavelka, Karel, Poor, Gyula, Rubbert-Roth, Andrea, Schulze-Koops, Hendrik, Strangfeld, Anja, Tanaka, Yoshiya, and Smolen, Josef S.

Published
2023

43. Machine learning identifies a profile of inadequate responder to methotrexate in rheumatoid arthritis

Author

Duquesne, Julien, Bouget, Vincent, Cournède, Paul Henry, Fautrel, Bruno, Guillemin, Francis, De Jong, Pascal H.P., Heutz, Judith W., Verstappen, Marloes, Van Der Helm-Van Mil, Annette H.M., Mariette, Xavier, Bitoun, Samuel, Duquesne, Julien, Bouget, Vincent, Cournède, Paul Henry, Fautrel, Bruno, Guillemin, Francis, De Jong, Pascal H.P., Heutz, Judith W., Verstappen, Marloes, Van Der Helm-Van Mil, Annette H.M., Mariette, Xavier, and Bitoun, Samuel

Abstract

Objectives: Around 30% of patients with RA have an inadequate response to MTX. We aimed to use routine clinical and biological data to build machine learning models predicting EULAR inadequate response to MTX and to identify simple predictive biomarkers. Methods: Models were trained on RA patients fulfilling the 2010 ACR/EULAR criteria from the ESPOIR and Leiden EAC cohorts to predict the EULAR response at 9 months (± 6 months). Several models were compared on the training set using the AUROC. The best model was evaluated on an external validation cohort (tREACH). The model's predictions were explained using Shapley values to extract a biomarker of inadequate response. Results: We included 493 therapeutic sequences from ESPOIR, 239 from EAC and 138 from tREACH. The model selected DAS28, Lymphocytes, Creatininemia, Leucocytes, AST, ALT, swollen joint count and corticosteroid co-treatment as predictors. The model reached an AUROC of 0.72 [95% CI (0.63, 0.80)] on the external validation set, where 70% of patients were responders to MTX. Patients predicted as inadequate responders had only 38% [95% CI (20%, 58%)] chance to respond and using the algorithm to decide to initiate MTX would decrease inadequate-response rate from 30% to 23% [95% CI: (17%, 29%)]. A biomarker was identified in patients with moderate or high activity (DAS28 > 3.2): patients with a lymphocyte count superior to 2000 cells/mm3 are significantly less likely to respond. Conclusion: Our study highlights the usefulness of machine learning in unveiling subgroups of inadequate responders to MTX to guide new therapeutic strategies. Further work is needed to validate this approach.

Published
2023

44. Hyperosmolar Environment and Salivary Gland Epithelial Cells Increase Extra-cellular Matrix Remodeling and Lymphocytic Infiltration in Sjögren’s Syndrome

Author

European Advanced Course and Conference on Immunology (Rouen), Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, Nocturne, Gaetane, European Advanced Course and Conference on Immunology (Rouen), Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, and Nocturne, Gaetane

Abstract

info:eu-repo/semantics/nonPublished

Published
2023

45. Fabrication and desired properties of conductive hydrogel dressings for wound healing

Author

Nie, Lei, Wei, Qianqian, Li, Jingyu, Deng, Yaling, He, Xiaorui, Gao, Xinyue, Mariette, Xavier, Liu, Shuang, Sun, Yanfang, Jiang, Guohua, Okoro, Oseweuba Valentine, Shavandi, Amin, Jing, Shengli, Nie, Lei, Wei, Qianqian, Li, Jingyu, Deng, Yaling, He, Xiaorui, Gao, Xinyue, Mariette, Xavier, Liu, Shuang, Sun, Yanfang, Jiang, Guohua, Okoro, Oseweuba Valentine, Shavandi, Amin, and Jing, Shengli

Abstract

Conductive hydrogels are recognized as promising materials for wound healing. Valuable properties of conductive hydrogels suggest the possibility of their use as an alternative wound dressing to traditional dressings such as bandages., info:eu-repo/semantics/published

Published
2023

46. Hyperosmolar environment and salivary gland epithelial cells increase extra-cellular matrix remodeling and lymphocytic infiltration in Sjögren’s syndrome.

Author

Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, Nocturne, Gaetane, Rivière, Elodie, Chivasso, Clara, Pascaud, Juliette, Bechara, Rami, Ly, Bineta, Delporte, Christine, Mariette, Xavier, and Nocturne, Gaetane

Abstract

Salivary gland epithelial cells (SGECs) play an active role in primary Sjogren's syndrome (pSS) pathogenesis. Quantitative and qualitative abnormalities of saliva might expose SGECs to chronic hyperosmolarity. We aimed to decipher the links between hyperosmolar stimulation of SGECs and lymphocytic infiltration of the salivary glands (SG) observed in pSS. RNAseq was performed on NS-SV-AC cells stimulated with hyperosmolar media containing NaCl (100 mM) or sucrose (200 mM), or with iso-osmolar (Iso) medium. RNAseq was performed on primary cultured SGECs from pSS and controls, in the presence or not of B cells. Hyperosmolar stimulation of NS-SV-AC-cells identified an upregulation of interferon-induced (MX1, IFIT2) and MMPs genes. Enrichment analysis revealed an over-representation of fibrosis pathway. In parallel, RNAseq of SGECs comparing pSS to controls identified an over-representation of a pathway involving MMPs. Given the unexpected upregulation of collagen (COL3A1, COL1A2) and ADAMTS genes in pSS SGECs, we hypothesized that SGECs might undergo epithelial-mesenchymal transition. ZEB2 was upregulated and SLUG was down regulated in SGECs from pSS versus controls. MMP24 and ZEB2 were higher in SGECs from pSS with a focus score ≥1 versus <1. Lastly, SGECs cocultured with B cells expressed higher levels of COL1A2. These results suggest the existence of a vicious circle. Alteration of SGECs in pSS participates in the establishment of a hyperosmolar microenvironment, which in turn promotes SGECs transcriptomic modifications. These modifications include extracellular matrix remodeling and promote SG lymphocytic infiltration., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

48. Identification of new candidate drugs for primary Sjögren's syndrome using a drug repurposing transcriptomic approach.

Author

Felten, Renaud, Ye, Tao, Schleiss, Cedric, Schwikowski, Benno, Sibilia, Jean, Monneaux, Fanny, Dumortier, Hélène, Jonsson, Roland, Lessard, Christopher, Ng, Fai, Takeuchi, Tsutomu, Mariette, Xavier, and Gottenberg, Jacques-Eric

Subjects
PHOSPHOTRANSFERASES, INTERFERONS, GENE expression profiling, INFORMATION resources, RESEARCH funding, SJOGREN'S syndrome, HISTONE deacetylase, LONGITUDINAL method
Abstract

Objectives To date, no immunomodulatory drug has demonstrated its efficacy in primary SS (pSS). We sought to analyse potential commonalities between pSS transcriptomic signatures and signatures of various drugs or specific knock-in or knock-down genes. Methods Gene expression from peripheral blood samples of patients with pSS was compared with that of healthy controls in two cohorts and three public databases. In each of the five datasets, we analysed the 150 most up- and downregulated genes between pSS patients and controls with regard to the differentially expressed genes resulting from the biological action on nine cell lines of 2837 drugs, 2160 knock-in and 3799 knock-down genes in the Connectivity Map database. Results We analysed 1008 peripheral blood transcriptomes from five independent studies (868 patients with pSS and 140 healthy controls). Eleven drugs could represent potential candidate drugs, with histone deacetylases and PI3K inhibitors among the most significantly associated. Twelve knock-in genes were associated with a pSS-like profile and 23 knock-down genes were associated with a pSS-revert profile. Most of those genes (28/35, 80%) were interferon-regulated. Conclusion This first drug repositioning transcriptomic approach in SS confirms the interest of targeting interferons and identifies histone deacetylases and PI3K inhibitors as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Association Between Bruton's Tyrosine Kinase Gene Overexpression and Risk of Lymphoma in Primary Sjögren's Syndrome.

Author

Duret, Pierre‐Marie, Schleiss, Cedric, Kawka, Lou, Meyer, Nicolas, Ye, Tao, Saraux, Alain, Devauchelle‐Pensec, Valérie, Seror, Raphaele, Larroche, Claire, Perdriger, Aleth, Sibilia, Jean, Vallat, Laurent, Fornecker, Luc‐Matthieu, Nocturne, Gaetane, Mariette, Xavier, and Gottenberg, Jacques‐Eric

Subjects
BLOOD testing, B cells, MULTIVARIATE analysis, GENE expression, PROTEIN-tyrosine kinases, GENE expression profiling, SJOGREN'S syndrome, CLUSTER analysis (Statistics), PREDICTION models, NON-Hodgkin's lymphoma
Abstract

Objective: We undertook this study to analyze whole blood gene expression and to investigate the role of B cell genes in primary Sjögren's syndrome–related non‐Hodgkin lymphoma (primary SS‐NHL). Methods: Peripheral whole blood samples were collected from 345 well‐phenotyped patients with primary SS enrolled in the prospective Assessment of Systemic Signs and Evolution in Sjögren's Syndrome (ASSESS) cohort. Transcriptomic analysis was performed using human Clariom S Arrays (Affymetrix). In our primary analysis, we considered patients with incident lymphoma (i‐primary SS‐NHL) as the case group and all patients without lymphoma as the comparison group. In our sensitivity analyses, we considered all patients with primary SS‐NHL, including those with a history of lymphoma (h‐primary SS‐NHL), as the case group and primary SS patients without lymphoma, stratified on their risk factors of lymphoma, as the comparison group. Results: Twenty‐one patients with primary SS‐NHL (including 8 with i‐primary SS‐NHL and 13 h‐primary SS‐NHL) were eligible for transcriptomic analysis; we compared these patients to 324 primary SS controls without lymphoma, including 110 with moderate to severe disease activity and 61 with no risk factor of lymphoma. Functional clustering analyses revealed an enrichment of genes related to innate and adaptive immunity, including B cell–related genes. Bruton's tyrosine kinase (BTK) and a proliferation‐inducing ligand (APRIL) genes were overexpressed before the occurrence of lymphoma in patients with incident lymphoma compared with patients without lymphoma. In sensitivity analyses, BTK was consistently up‐regulated across all comparisons performed. BTK expression was associated with risk of lymphoma on multivariate analyses, which considered 9 validated predictors of lymphoma in primary SS. Conclusion: BTK and APRIL were overexpressed in the peripheral blood of primary SS patients prior to lymphoma. The association between BTK, APRIL, and primary SS‐NHL requires confirmation in other prospective cohorts. [ABSTRACT FROM AUTHOR]

Published
2023
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