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24 results on '"Ignacio, Blanco"'

1. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

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Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. Rodero, Carlos Rodrigo, Luis Antonio Rodriguez, Carlos Rodriguez-Gallego, Agustí Rodriguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Damien Roux, Nikoletta Rovina, Flore Rozenberg, Yvon Ruch, Montse Ruiz, Maria Yolanda Ruiz del Prado, Juan Carlos Ruiz-Rodriguez, Joan Sabater-Riera, Kai Saks, Maria Salagianni, Oliver Sanchez, Adrián Sánchez-Montalvá, Silvia Sánchez-Ramón, Laire Schidlowski, Agatha Schluter, Julien Schmidt, Matthieu Schmidt, Catharina Schuetz, Cyril E. Schweitzer, Francesco Scolari, Luis Seijo, Analia Gisela Seminario, Piseth Seng, Sevtap Senoglu, Mikko Seppänen, Alex Serra Llovich, Virginie Siguret, Eleni Siouti, David M. Smadja, Nikaia Smith, Ali Sobh, Xavier Solanich, Jordi Solé-Violán, Catherine Soler, Betül Sözeri, Giulia Maria Stella, Yuriy Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Jean-Luc Taupin, Simon J. Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia

Subjects
HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Published
2024
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2. Antisense oligonucleotides targeting exon 11 are able to partially rescue the NF2-related schwannomatosis phenotype in vitro

Author

Núria Catasús, Inma Rosas, Sandra Bonache, Alex Negro, Miguel Torres-Martin, Adrià Plana-Pla, Hector Salvador, Eduard Serra, Ignacio Blanco, and Elisabeth Castellanos

Subjects
MT: oligonucleotides: therapies and applications, neurofibromatosis type 2, antisense therapy, antisense oligomers, genotype-phenotype correlations, Merlin, Therapeutics. Pharmacology, RM1-950
Abstract

NF2-related schwannomatosis (NF2-related SWN) is an autosomal dominant condition caused by loss of function variants in the NF2 gene, which codes for the protein Merlin and is characterized by the development of multiple tumors of the nervous system. The clinical presentation of the disease is variable and related to the type of the inherited germline variant. Here, we tested if phosphorodiamidate morpholino oligomers (PMOs) could be used to correct the splice signaling caused by variants at ±13 within the intron-exon boundary region and showed that the PMOs designed for these variants do not constitute a therapeutic approach. Furthermore, we evaluated the use of PMOs to decrease the severity of the effects of NF2 truncating variants with the aim of generating milder hypomorphic isoforms in vitro through the induction of the in-frame deletion of the exon-carrying variant. We were able to specifically induce the skipping of exons 4, 8, and 11 maintaining the NF2 gene reading frame at cDNA level. Only the skipping of exon 11 produced a hypomorphic Merlin (Merlin-e11), which is able to partially rescue the observed phenotype in primary fibroblast cultures from NF2-related SWN patients, being encouraging for the treatment of patients harboring truncating variants located in exon 11.

Published
2022
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3. Impact of hybrid immunity booster vaccination and Omicron breakthrough infection on SARS-CoV-2 VOCs cross-neutralization

Author

Edwards Pradenas, Silvia Marfil, Víctor Urrea, Macedonia Trigueros, Tetyana Pidkova, Anna Pons-Grífols, Raquel Ortiz, Carla Rovirosa, Ferran Tarrés-Freixas, Carmen Aguilar-Gurrieri, Ruth Toledo, Anna Chamorro, Marc Noguera-Julian, Lourdes Mateu, Ignacio Blanco, Eulàlia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Benjamin Trinité, and Julià Blanco

Subjects
Biochemistry, Immune response, Microbiology, Science
Abstract

Summary: The elicitation of cross-variant neutralizing antibodies against SARS-CoV-2 represents a major goal for current COVID-19 vaccine strategies. Additionally, natural infection may also contribute to broaden neutralizing responses. To assess the contribution of vaccines and natural infection, we cross-sectionally analyzed plasma neutralization titers of six groups of individuals, organized according to the number of vaccines they received and their SARS-CoV-2 infection history. Two doses of vaccine had a limited capacity to generate cross-neutralizing antibodies against Omicron variants of concern (VOCs) in uninfected individuals, but efficiently synergized with previous natural immunization in convalescent individuals. In contrast, booster dose had a critical impact on broadening the cross-neutralizing response in uninfected individuals, to level similar to hybrid immunity, while still improving cross-neutralizing responses in convalescent individuals. Omicron breakthrough infection improved cross-neutralization of Omicron subvariants in non-previously infected vaccinated individuals. Therefore, ancestral Spike-based immunization, via infection or vaccination, contributes to broaden SARS-CoV-2 humoral immunity.

Published
2023
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4. Deep genomic analysis of malignant peripheral nerve sheath tumor cell lines challenges current malignant peripheral nerve sheath tumor diagnosis

Author

Miriam Magallón-Lorenz, Ernest Terribas, Sara Ortega-Bertran, Edgar Creus-Bachiller, Marco Fernández, Gerard Requena, Inma Rosas, Helena Mazuelas, Itziar Uriarte-Arrazola, Alex Negro, Tereza Lausová, Elisabeth Castellanos, Ignacio Blanco, George DeVries, Hiroyuki Kawashima, Eric Legius, Hilde Brems, Viktor Mautner, Lan Kluwe, Nancy Ratner, Margaret Wallace, Juana Fernández-Rodriguez, Conxi Lázaro, Jonathan A. Fletcher, David Reuss, Meritxell Carrió, Bernat Gel, and Eduard Serra

Subjects
Biological sciences, Neuroscience, Cancer, Omics, Science
Abstract

Summary: Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas of the peripheral nervous system that develop either sporadically or in the context of neurofibromatosis type 1 (NF1). MPNST diagnosis can be challenging and treatment outcomes are poor. We present here a resource consisting of the genomic characterization of 9 widely used human MPNST cell lines for their use in translational research. NF1-related cell lines recapitulated primary MPNST copy number profiles, exhibited NF1, CDKN2A, and SUZ12/EED tumor suppressor gene (TSG) inactivation, and presented no gain-of-function mutations. In contrast, sporadic cell lines collectively displayed different TSG inactivation patterns and presented kinase-activating mutations, fusion genes, altered mutational frequencies and COSMIC signatures, and different methylome-based classifications. Cell lines re-classified as melanomas and other sarcomas exhibited a different drug-treatment response. Deep genomic analysis, methylome-based classification, and cell-identity marker expression, challenged the identity of common MPNST cell lines, opening an opportunity to revise MPNST differential diagnosis.

Published
2023
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5. ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1Research in context

Author

Charlotte Carton, D. Gareth Evans, Ignacio Blanco, Reinhard E. Friedrich, Rosalie E. Ferner, Said Farschtschi, Hector Salvador, Amedeo A. Azizi, Victor Mautner, Claas Röhl, Sirkku Peltonen, Stavros Stivaros, Eric Legius, Rianne Oostenbrink, Joan Brunet, Frank Van Calenbergh, Catherine Cassiman, Thomas Czech, María José Gavarrete de León, Henk Giele, Susie Henley, Conxi Lazaro, Vera Lipkovskaya, Eamonn R. Maher, Vanessa Martin, Irene Mathijssen, Enrico Opocher, Ana Elisabete Pires, Thomas Pletschko, Eirene Poupaki, Vita Ridola, Andre Rietman, Thorsten Rosenbaum, Alastair Santhouse, Astrid Sehested, Ian Simmons, Walter Taal, and Anja Wagner

Subjects
Guideline, Neurofibromatosis type 1, Tumour predisposing syndrome, Management, Medicine (General), R5-920
Abstract

Summary: Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder, predisposing development of benign and malignant tumours. Given the oncogenic potential, long-term surveillance is important in patients with NF1. Proposals for NF1 care and its specific manifestations have been developed, but lack integration within routine care. This guideline aims to assimilate available information on NF1 associated tumours (based on evidence and/or expert opinion) to assist healthcare professionals in undertaking tumour surveillance of NF1 individuals. Methods: By comprehensive literature review, performed March 18th 2020, guidelines were developed by a NF1 expert group and patient representatives, conversant with clinical care of the wide NF1 disease spectrum. We used a modified Delphi procedure to overcome issues of variability in recommendations for specific (national) health care settings, and to deal with recommendations based on indirect (scarce) evidence. Findings: We defined proposals for personalised and targeted tumour management in NF1, ensuring appropriate care for those in need, whilst reducing unnecessary intervention. We also incorporated the tumour-related psychosocial and quality of life impact of NF1. Interpretation: The guideline reflects the current care for NF1 in Europe. They are not meant to be prescriptive and may be adjusted to local available resources at the treating centre, both within and outside EU countries. Funding: This guideline has been supported by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). ERN GENTURIS is funded by the European Union. DGE is supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007).

Published
2023
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6. ERN GENTURIS tumour surveillance guidelines for individuals with neurofibromatosis type 1

Author

Charlotte Carton, D. Gareth Evans, Ignacio Blanco, Reinhard E. Friedrich, Rosalie E. Ferner, Said Farschtschi, Hector Salvador, Amedeo A. Azizi, Victor Mautner, Claas Röhl, Sirkku Peltonen, Stavros Stivaros, Eric Legius, Rianne Oostenbrink, Joan Brunet, Frank Van Calenbergh, Catherine Cassiman, Thomas Czech, María José Gavarrete de León, Henk Giele, Susie Henley, Conxi Lazaro, Vera Lipkovskaya, Eamonn R. Maher, Vanessa Martin, Irene Mathijssen, Enrico Opocher, Ana Elisabete Pires, Thomas Pletschko, Eirene Poupaki, Vita Ridola, Andre Rietman, Thorsten Rosenbaum, Alastair Santhouse, Astrid Sehested, Ian Simmons, Walter Taal, and Anja Wagner

Subjects
Tumour predisposing syndrome, General Medicine, Guideline, Management, Neurofibromatosis type 1
Abstract

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder, predisposing development of benign and malignant tumours. Given the oncogenic potential, long-term surveillance is important in patients with NF1. Proposals for NF1 care and its specific manifestations have been developed, but lack integration within routine care. This guideline aims to assimilate available information on NF1 associated tumours (based on evidence and/or expert opinion) to assist healthcare professionals in undertaking tumour surveillance of NF1 individuals. METHODS: By comprehensive literature review, performed March 18th 2020, guidelines were developed by a NF1 expert group and patient representatives, conversant with clinical care of the wide NF1 disease spectrum. We used a modified Delphi procedure to overcome issues of variability in recommendations for specific (national) health care settings, and to deal with recommendations based on indirect (scarce) evidence. FINDINGS: We defined proposals for personalised and targeted tumour management in NF1, ensuring appropriate care for those in need, whilst reducing unnecessary intervention. We also incorporated the tumour-related psychosocial and quality of life impact of NF1. INTERPRETATION: The guideline reflects the current care for NF1 in Europe. They are not meant to be prescriptive and may be adjusted to local available resources at the treating centre, both within and outside EU countries. FUNDING: This guideline has been supported by the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). ERN GENTURIS is funded by the European Union. DGE is supported by the Manchester NIHRBiomedical Research Centre (IS-BRC-1215-20007). ispartof: ECLINICALMEDICINE vol:56 ispartof: location:England status: published

Published
2023

7. Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison

Author

Bonaventura Clotet, Bàrbara Baro, Antoni E. Bordoy, Marc Corbacho-Monné, Oriol Estrada, Michael Marks, Nuria Prat, Andrea Alemany, Dan Ouchi, Camila G-Beiras, Pau Rodo, Oriol Mitjà, Maria Ubals, Sergi V. Salsench, Emilio N. Saya Amaro, Pere Millat-Martinez, Jordi Ara, Sònia Molinos, Martí Vall-Mayans, Quique Bassat, Marc Vilar, and Ignacio Blanco

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Silver, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Population, Antigen-detecting rapid diagnostic test, Roche Diagnostics, Gastroenterology, Asymptomatic, Sensitivity and Specificity, Article, 03 medical and health sciences, 0302 clinical medicine, Antigen, Internal medicine, medicine, Humans, 030212 general & internal medicine, education, Antigens, Viral, Asymptomatic Infections, Mass screening, Rapid diagnostic test, education.field_of_study, business.industry, SARS-CoV-2, Diagnostic Tests, Routine, COVID-19, Benchmarking, Infectious Diseases, Head-to-head comparison, medicine.symptom, business
Abstract

Background: Mass testing for early identification and isolation of infectious COVID-19 individuals is efficacious for reducing disease spread. Antigen-detecting rapid diagnostic tests (Ag-RDT) may be suitable for testing strategies; however, benchmark comparisons are scarce. Methods: We used 286 nasopharyngeal specimens from unexposed asymptomatic individuals collected between December 2020 and January 2021 to assess five Ag-RDTs marketed by Abbott, Siemens, Roche Diagnostics, Lepu Medical, and Surescreen. Results: For the overall sample, the performance parameters of Ag-RDTs were as follows: Abbott assay, sensitivity 38.6% (95%CI 29.1-48.8) and specificity 99.5% (97-100%); Siemens, sensitivity 51.5% (41.3-61.6) and specificity 98.4% (95.3-99.6); Roche, sensitivity 43.6% (33.7-53.8) and specificity 96.2% (92.4-98.5); Lepu, sensitivity 45.5% (35.6-55.8) and specificity 89.2% (83.8-93.3%); Surescreen, sensitivity 28.8% (20.2-38.6) and specificity 97.8% (94.5-99.4%). For specimens with cycle threshold (Ct) = 70%. The modelled negative- and positive-predictive value for 1% prevalence were >99% and 80% for specimens with Ct= 96%. The estimated negative predictive value suggests the suitability of Ag-RDTs for mass screenings of SARS-CoV-2 infection in the general population. (C) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Published
2021

8. Serpins and Serpinopathies

Author

Ignacio Blanco

Subjects
0301 basic medicine, animal structures, Protease, medicine.medical_treatment, Pseudogene, Biology, Serpin, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Biochemistry, 030220 oncology & carcinogenesis, embryonic structures, medicine, Hormone transport, Familial encephalopathy with neuroserpin inclusion bodies, Gene, Loss function, Function (biology)
Abstract

Serpin (an acronym for the terms ser ine p roteinase in hibitor) superfamily comprises a structurally similar set of proteins, which were originally called with this acronym by its firstly known function as protease inhibitors. However, it was found later that some of its members are involved in proteins folding, storage, and transport. Thirty-five coding genes and five pseudogenes of serpins have been found in most tissues throughout the human body. Although most serpins are extracellular, there are also some intracellularly localized serpins, all together taking pivotal roles in digestion, coagulation, fibrinolysis, complement regulation, inflammation, apoptosis, angiogenesis, tumor suppression, and hormone transport. Serpinopathies result from point mutations in some serpin members, characterized by the formation of polymers that are retained within the synthesizing cells–this fact causing disease by a “toxic gain of function” from the intracellular accumulated protein and a “loss of function” as a result of the deficiency of inhibitors that control proteolytic cascades.

Published
2017
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9. Alpha-1 Antitrypsin Biology

Author

Ignacio Blanco

Subjects
Proteases, biology, Plasmin, Neutrophil elastase, Elastase, biology.protein, Chymase, Proteolytic enzymes, medicine, Tryptase, Kallikrein, Molecular biology, medicine.drug
Abstract

Alpha-1 antitrypsin (AAT) is an acute phase protein mainly produced by liver. Its main function is to protect lungs from neutrophil elastase, a potent protease that degrades elastin and other connective tissue components. Besides elastase, its spectrum of action extends to many other proteolytic enzymes (including proteinase-3, cathepsin-G, and defensins-α from neutrophils; chymase and tryptase from mast cells; trypsin, chymotrypsin, and elastase from pancreas; granzyme B from T-lymphocytes; and the circulating serine proteases plasmin, thrombin, plasminogen activator 1&2, factor Xa, and kallikreins 7&14), providing to human serum more than 90% of its antiprotease capacity. Incidentally, the neutralization of serine proteases prevents activation of tissue proenzymes, such as metalloproteinases, kallikreins, or cathepsins, as well as the transmembrane protease-activated receptors (PARs) expressed throughout the body, thereby controlling the intensity and resolution of inflammation. In addition, AAT regulates the activity of various key cells of the immune system, such as neutrophils, lymphocytes, monocytes, macrophages, and mast cells, as well as fibroblasts, endothelial, and epithelial cells. These capabilities together provide to AAT multiple antiinflammatory, immunomodulatory, and antimicrobial properties.

Published
2017
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10. Current Research and Future Perspectives

Author

Ignacio Blanco

Subjects
Clinical trial, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Pathology, business.industry, Fda approval, Antisense oligonucleotides, medicine, Intensive care medicine, business
Abstract

After the discovery of the alpha-1 antitrypsin (AAT) deficiency (AATD) little more than half a century ago, there has been a remarkable progress in the knowledge of its pathophysiological mechanisms, laboratory diagnosis, and clinical management of the patients with this inherited condition. Undoubtedly, one of the most important practical advances has been the FDA approval of plasma-derived AAT augmentation therapy for AATD-associated COPD 30 years ago in the United States, a specific therapy that later spread to other countries.

Published
2017
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11. Respiratory Manifestations of the Alpha-1 Antitrypsin Deficiency

Author

Ignacio Blanco

Subjects
COPD, medicine.medical_specialty, Chronic bronchitis, Pathology, Alpha 1-antitrypsin deficiency, Bronchiectasis, business.industry, medicine.disease, Gastroenterology, respiratory tract diseases, Pulmonary function testing, Internal medicine, medicine, Lung emphysema, Respiratory system, business, Asthma
Abstract

The term “chronic obstructive pulmonary disease” (COPD) encompasses lung emphysema and chronic bronchitis, and is the most typical clinical manifestation of the alpha-1 antitrypsin (AAT) deficiency (AATD), a hereditary condition which mainly affects Caucasians and is behind of approximately 3% of all COPD cases. The causal relationship between AATD and bronchiectasis or bronchial asthma is unproved. Smoking is the major etiologic factor that can accelerate the development of COPD. The onset of respiratory symptoms (i.e., dyspnea, cough, expectoration, wheezing, etc.) in smokers begins between ages 35 and 45 years, while in nonsmokers this onset may be delayed until the fifth or sixth decade of life. In most patients, the chest X-ray shows emphysematous changes in the bases, and in about a quarter CT scan can also show clinically significant bronchiectasis. Lung function tests show an obstructive pattern (with partial reversibility in some cases) and a reduced diffusion capacity. At least 95% of all cases are Pi*ZZ individuals expressing very low concentrations of AAT, insufficient to prevent the degradation of elastin in the alveolar walls by neutrophil proteases. Underdiagnoses, misdiagnosis, and delayed diagnosis remain the biggest obstacles to prevent the high rate of disability and mortality associated with this disease.

Published
2017
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12. Genetic Epidemiology

Author

Ignacio Blanco

Subjects
medicine.medical_specialty, education.field_of_study, Alpha 1-antitrypsin deficiency, Population, Ethnic group, Biology, medicine.disease, Increased risk, Genetic epidemiology, Epidemiology, Genotype, medicine, Allele, education, Demography
Abstract

The present chapter focuses on the epidemiology of the most common alpha-1 antitrypsin (AAT) deficiency (AATD) alleles, that is, Pi*S and Pi*Z. Although some of the available data on Pi*S and Pi*Z frequencies may be distorted by bias related to the samples size and its composition (most of them constituted by subjects not entirely representative of the general population), or to an inadequate diagnostic methodology, currently there are available data of around 250 cohorts with approximately 200,000 subjects from all races and continents worldwide, with which a global perspective of the AATD distribution worldwide can be described. Unfortunately, there is insufficient data on frequency, prevalence, and geographical distribution of the very uncommon AATD “rare” and “null” alleles. According to the reported estimates, there could be at least 250,000 Pi*ZZ individuals (mostly of Caucasian ethnicity) at high risk for developing diseases related to AATD, with Europe having around of 115,000 of these individuals, and The United States and Canada over 70,000. In addition, there may be around of 1,300,000 Pi*SZ (most of them Caucasians), at increased risk but clearly lower than that of the Pi*ZZ subjects, 48% living in Northern, Western, and Central Europe, 20% in North and Central America, and 16% in South America.

Published
2017
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13. Alpha-1 Antitrypsin Deficiency: Introduction and History

Author

Ignacio Blanco

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Pathology, Cirrhosis, Alpha 1-antitrypsin deficiency, business.industry, Pulmonary emphysema, AAT deficiency, Context (language use), medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, Lung emphysema, 030212 general & internal medicine, Panniculitis, business, Systemic vasculitis
Abstract

After the discovery of the alpha-1 antitrypsin (AAT) deficiency–related lung emphysema by Laurell and Ericksson in Malmo (Sweden) 52 years ago, it took nearly a decade to discover its relationship with liver cirrhosis and neutrophilic panniculitis. Almost 30 years ago (1987), the US Food and Drugs Administration (FDA) approved Prolastin (purified AAT obtained from pooled human serum) for augmentation therapy in patients with severe AAT deficiency, suffering from pulmonary emphysema. In the 1990s, systemic vasculitis was added to the initial list of AAT deficiency–related diseases, and since then powerful patients’ associations and registries were created worldwide with the aim of promoting research and facilitating the patients’ diagnosis and access to treatment of this genetic condition. In the last 15 years, a growing number of new AAT antiinflammatory and immunomodulatory properties have been identified, suggesting multiple potential indications for a number of diseases, both inside and outside of the context of AAT deficiency. Lately the most advanced lines of research have been implemented using this condition as a model with the ultimate goal of achieving a cure. This introductory chapter aims to be a general introduction to the basic aspects of the AAT deficiency and to briefly report its exciting exemplary history.

Published
2017
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14. Alpha-1 Antitrypsin Deficiency: Lung Pathophysiology

Author

Ignacio Blanco

Subjects
COPD, Alpha 1-antitrypsin deficiency, Lung, biology, business.industry, Inflammation, respiratory system, medicine.disease, Systemic inflammation, respiratory tract diseases, Alveolar cells, medicine.anatomical_structure, Neutrophil elastase, Immunology, medicine, biology.protein, Lung emphysema, medicine.symptom, business
Abstract

Chronic obstructive pulmonary disease (COPD) associated to alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by a low blood and lung tissues AAT concentration, a high neutrophil elastase load, and a high neutrophil burden in the airways of affected individuals. The most important factor in the pathogenesis of AATD-related COPD is a disturbance of the physiological balance between proteases and antiproteases that may cause lung emphysema. Oxidative stress is another important pathophysiological factor. Tumor necrosis factor alpha (TNF-α) signaling is as well a major player in the pathogenesis of COPD, impairing neutrophil activity, and enhancing chemotaxis and migration of neutrophils by inducing expression of IL-8 in alveolar epithelial cells while upregulating endothelial adhesion molecules in sites of inflammation and tissue injury. The development of emphysema may also involve a loss of alveolar cells by an abnormally accelerated apoptosis. Protein Z polymers accumulation triggering a endoplasmic reticulum stress reaction in epithelial alveolar and bronchial cells can also contribute to lung injure in Pi*ZZ individuals. As it just occurs in common COPD, autoimmunity may play a major pathogenic role in some AATD-related COPD patients. Finally, a systemic inflammation induced by COPD may be of relevance to the development of systemic comorbidities in some patients suffering from AATD-related COPD.

Published
2017
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15. Clinical Diagnosis

Author

Ignacio Blanco

Subjects
medicine.medical_specialty, COPD, Cirrhosis, Alpha 1-antitrypsin deficiency, business.industry, Incidence (epidemiology), medicine.disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, 030228 respiratory system, Hepatocellular carcinoma, Internal medicine, Medicine, 030212 general & internal medicine, business, Panniculitis, Systemic vasculitis
Abstract

Alpha-1 antitrypsin (AAT) deficiency (AATD) is an underrecognized relatively common genetic condition among white persons that typically predisposes to the development of early onset chronic obstructive pulmonary disease (COPD), liver cirrhosis and exceptionally hepatocellular carcinoma, systemic vasculitis, and neutrophilic panniculitis. Approximately 1%–3% of COPD patients, most undiagnosed, are estimated to have AATD. Smoking is the major factor influencing the course of the AATD-related COPD. Progressive dyspnoea, cough, expectoration, and wheezing are the primary symptoms. In smokers, the onset of symptoms occurs in the third or fourth decade of life, whereas in nonsmokers they are delayed until the sixth decade. Remarkably, a small number of nonsmokers never manifest symptoms and have a normal life-span. Liver disease affects a small portion of children, manifesting as obstructive jaundice and cirrhosis in the early months of life. The incidence of liver disease increases with age and cirrhosis in adults may occur in absence of childhood liver disease. The risk for hepatocellular carcinoma is increased in older AATD individuals. Rarely AATD is associated with systemic vasculitis or neutrophilic panniculitis. Targeted detection of AATD has been advocated by official society guidelines. Traditionally, the diagnosis relies on demonstration of a low serum concentration of AAT usually assessed by nephelometry, followed by isoelectric focusing (IEF) and gene sequencing when necessary. Alternatively, many laboratories use dried blood spot samples to measure the AAT concentration, to investigate S and Z proteins, and even to perform IEF and gene sequencing. Currently, most authors advocate using a combination of laboratory methods (including IEF and/or sequencing) to detect clinically relevant mutations.

Published
2017
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16. Liver Disease Associated With Alpha-1 Antitrypsin Deficiency

Author

Ignacio Blanco

Subjects
medicine.medical_specialty, Cirrhosis, Alpha 1-antitrypsin deficiency, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Incidence (epidemiology), Endoplasmic reticulum, Liver transplantation, medicine.disease, Gastroenterology, Liver disease, Cholestasis, Internal medicine, Immunology, medicine, business, Liver function tests
Abstract

The typical molecular defect of the alpha-1 antitrypsin (AAT) deficiency (AATD) is a single-base mutation of the SERPINA1 gene leading to the synthesis of an abnormal protein that polymerizes in the endoplasmic reticulum of hepatocytes, causing intracellular stress and liver damage. There is high variability in the clinical manifestation among AATD patients, suggesting a strong influence of other genetic and environmental modifiers. Ninety-nine percent of the reported cases of AATD-related liver disease are Pi*ZZ. In 10% of Pi*ZZ children, the condition may become evident by the appearance of intrahepatic cholestasis (long-term obstructive jaundice). Among these, 2.5% develop childhood–adolescent cirrhosis that may require liver transplantation. Around one-third of Pi*ZZ adult patients (mostly men) develops chronic hepatitis or liver cirrhosis, whose incidence increases in parallel with age: 10% in those aged

Published
2017
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17. Registries and Patients’ Associations

Author

Ignacio Blanco

Subjects
Natural history, Clinical trial, Pediatrics, medicine.medical_specialty, business.industry, Family medicine, Health care, medicine, business, World health
Abstract

Severe alpha-1 antitrypsin (AAT) deficiency (AATD) is an uncommon condition, typically linked to Pi*Z genotypes, included in the long list of rare diseases. Its low frequency and underdiagnoses are still major handicaps to properly understand and manage it. Registries are powerful tools to improve understanding of the natural history of rare diseases, and in addition they are extremely useful for recruiting patients for clinical trials that otherwise could not be performed. In the late 1980s the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health from the United States developed a prospective registry which enrolled individuals with severe AATD from 1989 to 1992, both on or off augmentation therapy, and followed them until 1996. The resulting dataset of 1129 individuals has allowed a better understanding of the natural history of AATD. When the NHLBI Registry ended, a community of patients and health care professionals joined to successively constitute the Alpha-1 Foundation, AlphaNet, and the Alpha-1 Foundation Research Registry. Almost simultaneously, in 1996, a World Health Organization meeting recommended the establishment of national and international registries to facilitate data collection and collaborative research, as well as helping to create a patient resource bank for the design and conduct powered clinical trials. To comply with these recommendations, several key opinion leaders in Europe established the Alpha One International Registry (AIR), initially founded by uniting the already existing European national registries and later adding other registries from various countries around the world.

Published
2017
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18. Clinical Management and Treatment of Lung Disease

Author

Ignacio Blanco

Subjects
Spirometry, medicine.medical_specialty, COPD, Alpha 1-antitrypsin deficiency, Passive smoking, medicine.diagnostic_test, business.industry, medicine.medical_treatment, medicine.disease, medicine.disease_cause, Obstructive lung disease, respiratory tract diseases, Pulmonary function testing, Internal medicine, Diffusing capacity, medicine, Physical therapy, Lung transplantation, business
Abstract

Alpha-1 antitrypsin (AAT) deficiency (AATD)-associated COPD (AATD-COPD) must be managed along the general lines already set out in international standards, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD). It is very important that patients avoid both active and passive smoking, occupations with exposure to environmental pollutants, mineral dust, gas, and fumes. To lessen the progression of the lung disease, intravenous augmentation therapy to raise baseline serum AAT concentrations above a protective level of 11 μM/L (or 60 mg/dL) should be assessed by medical experts for AATD individuals with established fixed airflow obstruction. Lung transplantation may be an appropriate option for individuals with end-stage lung disease. Yearly vaccination against influenza and pneumococcus is recommended. All individuals with severe AATD should periodically undergo a medical examination with pulmonary function tests, including spirometry and diffusing capacity measurements. A chest X-ray should be performed to rule out other pathologies, and computed tomography (CT) should be considered in selected cases. Parents, siblings, and offspring of an individual with severe AATD should be evaluated to identify as early as possible those relatives who would benefit from preventive and therapeutic measures.

Published
2017
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19. Alpha-1 Antitrypsin Gene, Genetic Heritage, Phenotypes, and Genotypes

Author

Ignacio Blanco

Subjects
Genetics, education.field_of_study, Alpha 1-antitrypsin deficiency, Population, Biology, medicine.disease, Null allele, symbols.namesake, Exon, Genotype, Mendelian inheritance, symbols, medicine, Allele, education, Gene
Abstract

Human alpha-1 antitrypsin (AAT) is codified by the SERPINA1 (serine peptidase inhibitor, clade A, member 1) gene, located on chromosome 14q32. This gene is organized into three noncoding exons (1A, 1B, and 1C), four coding exons (II–V), and six introns, and it is transmitted from parents to children by simple Mendelian inheritance by two alleles (one from each parent) that express at 50% in each child. Approximately 125 genetic variants have been described in humans so far, and for clinical purposes they have been classified into four major categories, namely normal, deficiency, null, and dysfunctional variants. Most genotypes are resulting from the combination of the normal allele M and the S and Z deficiency alleles, that is, Pi*MM, Pi*MS, Pi*SS, Pi*MZ, PI*SZ, and Pi*ZZ, with a mean frequency in the general population worldwide of 95.8% for Pi*MM, 2.8% for Pi*MS, 0.6% for Pi*MZ, 0.6% for Pi*SS, 0.2% for Pi*SZ, and 0.004% for Pi*ZZ, but with large differences in these percentages between races and ethnic groups due to a much higher prevalence of the S and Z alleles in Caucasians than in African, Asian, or Native Americans subjects. Reduced serum levels of the AAT protein are commonly associated with the deficient S and Z alleles, but there are also approximately 25 rare deficiency alleles that produce very small amounts of AAT, as well as approximately other 25 null alleles that virtually do not express AAT.

Published
2017
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20. Other Diseases Associated With Alpha-1 Antitrypsin Deficiency

Author

Ignacio Blanco

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Alpha 1-antitrypsin deficiency, business.industry, Disease, medicine.disease, Inflammatory bowel disease, Liver disease, Rheumatoid arthritis, Immunology, Medicine, Respiratory system, business, Panniculitis, Granulomatosis with polyangiitis
Abstract

Alpha-1 antitrypsin (AAT) deficiency (AATD) has a highly variable clinical presentation, ranging from no disease symptoms to the well-known AATD-related respiratory and liver disease manifestations, and the less common but well-established granulomatosis with polyangiitis (GPA) and neutrophilic panniculitis diseases.

Published
2017
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21. Capacidad predictiva del modelo BCRAPro frente al profesional de enfermería en la selección de candidatos a estudio genético de cáncer de mama u ovario hereditario

Author

Sílvia Iglesias-Casals, Carmen Yagüe-Muñoz, Àlex Teulé-Vega, Ignacio Blanco, Llúcia Benito-Aracil, Mònica Salinas-Masdeu, Conxi Lázaro-García, and Universitat de Barcelona

Subjects
Breast cancer, Infermeria, Ovarian cancer, Càncer d'ovari, Malalties hereditàries, Genetics, General Medicine, Nursing, General Nursing, Genètica, Càncer de mama, Genetic diseases
Abstract

Resumen Objetivo Comparar la capacidad predictiva del modelo predictivo BRCAPro y de los profesionales de enfermeria con distintos niveles de formacion/experiencia en la identificacion de familias susceptibles de ser estudiadas geneticamente dada su historia personal y familiar de cancer de mama. Metodo Estudio descriptivo en el que 2 enfermeras con diferente grado de formacion en consejo genetico han estimado la probabilidad de ser portador de mutacion en los genes BRCA1/BRCA2 de 157 familias. Se calculo la sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN) de ambas enfermeras y del BRCAPro. Resultados La enfermera con menor experiencia demostro mayor especificidad (N2:0,84) frente a la enfermera con mayor experiencia (N1:0,23) o a BRCAPro (0,47). La sensibilidad de las profesionales de enfermeria fue de 0,95 (N1) y del 0,28 (N2), mientras que la de BRCAPro fue del 0,74. El VPP fue similar en las tres situaciones. El VPN de la enfermera con mayor experiencia (0,93) fue superior al de BRCAPro (0,85) y la enfermera con menor experiencia (0,72). Conclusiones La experiencia clinica aporta una alta sensibilidad pero a costa de una perdida significativa de especificidad. El modelo de prediccion BRCAPro obtiene valores intermedios entre ambas enfermeras, por lo que podria ser una herramienta que ayudase a mejorar aquellos valores en los que se obtiene menor puntuacion, es decir, la especificidad y VPP para enfermeras con mayor experiencia y la sensibilidad y VPN para aquellas con menor experiencia.

Published
2010

22. Allele-Specific Expression of APC in Adenomatous Polyposis Families

Author

Gabriel Capellá, Ester Castellsagué, Sara González, Conxi Lázaro, Elisabet Guinó, Kristen N. Stevens, Ignacio Blanco, Stephen B. Gruber, Ester Borras, Victoria M. Raymond, and Universitat de Barcelona

Subjects
Genes, APC, Adenomatous polyposis coli, RNA Stability, DNA Mutational Analysis, Single-nucleotide polymorphism, Allelic Imbalance, medicine.disease_cause, Article, Genètica molecular, Familial adenomatous polyposis, DNA Glycosylases, Exon, Germline mutation, MUTYH, Risk Factors, Càncer colorectal, medicine, Humans, Genetic Predisposition to Disease, RNA, Messenger, Molecular genetics, Promoter Regions, Genetic, Germ-Line Mutation, Genetics, Mutation, Hepatology, biology, Gastroenterology, Exons, medicine.disease, Expressió gènica, Colorectal cancer, Pedigree, Fenotip, Phenotype, Attenuated familial adenomatous polyposis, Adenomatous Polyposis Coli, biology.protein, Gene expression
Abstract

Background & Aims Germline mutations in the APC gene cause of most cases of familial adenomatous polyposis (FAP) and a lesser proportion of attenuated FAP (AFAP). Systematic analysis of APC at the RNA level could provide insight into the pathogenicity of identified mutations and the molecular basis of FAP/AFAP in families without identifiable mutations. Here, we analyzed the prevalence of imbalances in the allelic expression of APC in polyposis families with germline mutations in the gene and without detectable mutations in APC and/or MUTYH . Methods Allele-specific expression (ASE) was determined by single nucleotide primer extension using an exon 11 polymorphism as an allele-specific marker. In total, 52 APC -mutation–positive (36 families) and 24 APC/MUTYH -mutation–negative (23 families) informative patients were analyzed. Seventy-six controls also were included. Results Of the APC -mutation–positive families, most of those in whom the mutation was located before the last exon of the gene (12 of 14) had ASE imbalance, which is consistent with a mechanism of nonsense-mediated decay. Of the APC/MUTYH -mutation–negative families, 2 (9%) had ASE imbalance, which might cause the disease. Normal allele expression was restored shortly after lymphocytes were cultured with puromycin, supporting a ‘nonsense-mediated' hypothesis. Conclusions ASE analysis might be used to determine the pathogenesis of some cases of FAP and AFAP in which APC mutations are not found. ASE also might be used to prioritize the order in which different areas of APC are tested. RNA-level studies are important for the molecular diagnosis of FAP.

23. Reprogramming Captures the Genetic and Tumorigenic Properties of Neurofibromatosis Type 1 Plexiform Neurofibromas

Author

Meritxell Carrió, Helena Mazuelas, Yvonne Richaud-Patin, Bernat Gel, Ernest Terribas, Imma Rosas, Senda Jimenez-Delgado, Josep Biayna, Leen Vendredy, Ignacio Blanco, Elisabeth Castellanos, Conxi Lázaro, Ángel Raya, and Eduard Serra

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Summary: Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disease caused by mutations in the NF1 tumor suppressor gene. Plexiform neurofibromas (PNFs) are benign Schwann cell (SC) tumors of the peripheral nerve sheath that develop through NF1 inactivation and can progress toward a malignant soft tissue sarcoma. There is a lack of non-perishable model systems to investigate PNF development. We reprogrammed PNF-derived NF1(−/−) cells, descendants from the tumor originating cell. These NF1(−/−)-induced pluripotent stem cells (iPSCs) captured the genomic status of PNFs and were able to differentiate toward neural crest stem cells and further to SCs. iPSC-derived NF1(−/−) SCs exhibited a continuous high proliferation rate, poor myelination ability, and a tendency to form 3D spheres that expressed the same markers as their PNF-derived primary SC counterparts. They represent a valuable model to study and treat PNFs. PNF-derived iPSC lines were banked for making them available. : In this article, Eduard Serra and colleagues describe the generation of iPSCs directly from plexiform neurofibromas (PNFs), benign Schwann cell (SC) tumors associated with neurofibromatosis type 1. iPSCs bearing the double inactivation of the NF1 gene were differentiated into SCs that exhibited a high proliferation rate, a poor myelination ability, and a tendency to form spheres, resembling PNF-derived SCs. Keywords: iPSC, neurofibromatosis type 1, plexiform neurofibroma, Schwann cell, neural crest stem cell, NF1, benign tumor

Published
2019
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24. Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model.

Author

Na KS, Fernandes-Cunha GM, Varela IB, Lee HJ, Seo YA, and Myung D

Subjects
Alkalies, Animals, Biocompatible Materials, Collagen, Cornea, Hydrogels, Organ Culture Techniques, Polyethylene Glycols, Rabbits, Mesenchymal Stem Cells
Abstract

Background Aims: Corneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs., Methods: Human MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels., Results: All corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels., Conclusions: PEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries., (Published by Elsevier Inc.)

Published
2021
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