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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. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Author

Bella Shadur, Andrew R. Gennery, Nurcicek Padem, Anna Mukhina, Polina Stepensky, Svetlana O. Sharapova, Sara Sebnem Kilic, Magdalena Avbelj Stefanija, Luis I. Gonzales-Granado, Isabelle Meyts, Jacques G. Rivière, Filomeen Haerynck, Joachim Zobel, Benoit Florkin, Laura Gamez, Vedat Uygun, Nicolette Moes, Neslihan Edeer Karaca, Lennart Hammarström, Anke M.J. Peters, Bodo Grimbacher, Sevgi Köstel Bal, Aydan Ikinciogullari, Zahra Chavoshzadeh, Joris M. van Montfrans, Sule Haskologlu, Hassan Abolhassani, Necil Kutukculer, Safa Baris, Yuliya Mareika, Juan Luis Santos Perez, Elif Karakoc-Aydiner, Asghar Aghamohammadi, Mehdi Adeli, Antonio Marzollo, Hermann J. Girschick, Sevgi Keles, Amer Khojah, Shahrzad Bakhtiar, Victoria Katharina Tesch, Anna Shcherbina, Antonios G.A. Kolios, Marie Meeths, Mikko Seppänen, Austen Worth, Marina Garcia-Prat, Figen Dogu, Arjan C. Lankester, Markus G. Seidel, European Soc Blood, European Soc Immunodeficiencies, University of Zurich, Tesch, Victoria Katharina, Abolhassani, Hassan, Shadur, Bella, Zobel, Joachim, Mareika, Yuliya, Sharapova, Svetlana, Karakoc-Aydiner, Elif, Riviere, Jacques G., Garcia-Prat, Marina, Moes, Nicolette, Haerynck, Filomeen, Gonzales-Granado, Luis I., Santos Perez, Juan Luis, Mukhina, Anna, Shcherbina, Anna, Aghamohammadi, Asghar, Hammarstrom, Lennart, Dogu, Figen, Haskologlu, Sule, Ikinciogullari, Aydan I., Bal, Sevgi Kostel, Baris, Safa, Kilic, Sara Sebnem, Karaca, Neslihan Edeer, Kutukculer, Necil, Girschick, Hermann, Kolios, Antonios, Keles, Sevgi, Uygun, Vedat, Stepensky, Polina, Worth, Austen, van Montfrans, Joris M., Peters, Anke M. J., Meyts, Isabelle, Adeli, Mehdi, Marzollo, Antonio, Padem, Nurcicek, Khojah, Amer M., Chavoshzadeh, Zahra, Stefanija, Magdalena Avbelj, Bakhtiar, Shahrzad, Florkin, Benoit, Meeths, Marie, Gamez, Laura, Grimbacher, Bodo, Seppanen, Mikko R. J., Lankester, Arjan, Gennery, Andrew R., Seidel, Markus G., Ege Üniversitesi, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk İmmünoloji., Kılıç, Sara Şebnem, AAH-1658-2021, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, TRIMM - Translational Immunology Research Program, Research Programs Unit, University of Helsinki, and HUS Inflammation Center

Subjects
Male, Neurologic disease, medicine.medical_treatment, Autoimmunity, Hematopoietic stem cell transplantation, Treatment response, Eye disease, 0302 clinical medicine, Thrombotic thrombocytopenic purpura, Azathioprine, combined immunodeficiency, Disease activity, Treatment outcome, Disease course, Child, Inborn error of immunity (IEI), Immunodeficiency, combined, Hematopoietic Stem Cell Transplantation, combined immunodeficiency (CID), hematopoietic stem cell transplantation (HSCT), Tocilizumab, Signal transducing, Multicenter study, Immunologic deficiency syndromes, 3. Good health, Clinical trial, Retrospective study, sirolimus, Child, Preschool, Cyclosporine, 2723 Immunology and Allergy, Graft failure, Lung infection, hematopoietic stem, Cohort analysis, Longitudinal study, Rituximab, Infection, Human, Hepatomegaly, medicine.medical_specialty, Genotype, Immunology, Cause of death, Major clinical study, Article, 03 medical and health sciences, Signal transducing adaptor protein, Humans, Lipopolysaccharide responsive beige like anchor protein deficiency, cell transplantation, Aged, 2403 Immunology, MUTATIONS, Abatacept, Immunologic Deficiency Syndromes, Adalimumab, Failure to thrive, Follow up, Survival analysis, Immune dysregulation, medicine.disease, Survival Analysis, 030104 developmental biology, Disease activity score, Splenomegaly, 10033 Clinic for Immunology, School child, Human medicine, immunodeficiency, 0301 basic medicine, Thyroiditis, Allergy, Unclassified drug, Immune deficiency, Lipopolysaccharide responsive beige like anchor protein, Respiratory failure, Skin manifestation, medicine.disease_cause, Lymphocyte proliferation, Medicine and Health Sciences, Immunology and Allergy, Overall survival, Middle aged, performance scale, Interstitial pneumonia, Priority journal, CTLA4, Mycophenolate mofetil, Chloroquine, clinical score, Immunosuppression, Disease burden, Transplant-Related Mortality, Middle Aged, Acute graft versus host disease, Hospitalization, Immune deficiency and dysregulation activity score, Treatment Outcome, Phenotype, surgical procedures, operative, primary immunodeficiency disorder (PID), hematopoietic stem cell transplantation, Female, medicine.drug, Adult, dysregulation, Malabsorption, abatacept, Adolescent, Child, preschool, Pemission, Interstitial lung disease, 610 Medicine & health, LRBA, Young Adult, immune dysregulation, Internal medicine, Adaptor proteins, medicine, primary immunodeficiency disorder, Mycophenolic acid, Rapamycin, Mortality, Disease severity, Adaptor Proteins, Signal Transducing, Inborn error of immunity, Chimera, business.industry, Protein, Retrospective cohort study, LRBA protein, Multiple organ failure, Infliximab, Immunosuppressive treatment, Young adult, Preschool child, 3121 General medicine, internal medicine and other clinical medicine, Common Variable Immunodeficiency, Immunoglobulin Deficiency, immune, business, 030215 immunology
Abstract

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. the overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). in contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: the lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT., Styrian Children's Cancer Aid Foundation; Slovenian Research AgencySlovenian Research Agency - Slovenia [P3-0343]; Jonas S_oderquist Foundation; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [217S847, 318S202]; Deutsche Forschungsgemeinschaft under Germany's Excellence StrategyGerman Research Foundation (DFG) [390939984, 39087428]; E-Rare program of the European Union by the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GR1617/14-1/iPAD]; Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research [GAIN_ 01GM1910A]; Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital; Graduate Research Training Scholarship of the Australian government; Hadassah Australia; ERN-RITA network [739543], M.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children's Cancer Aid Foundation. M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343). H. Abolhassani was supported by the Jonas S_oderquist Foundation. S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155-Project ID 39087428); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A). M.R.J. Sepp_anen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital. I. Meyts is a member of the ERN-RITA network (project identification number 739543). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia.

Published
2020

3. Pneumococcal antibody levels in children with PID receiving immunoglobulin

Author

Christophe Chantrain, Paul Strengers, Pierre Philippet, Benoit Florkin, Ruth Laub, Iris De Schutter, Filomeen Haerynck, David Tuerlinckx, Alina Ferster, Pediatrics, and Growth and Development

Subjects
Adult, Male, Adolescent, Enzyme-Linked Immunosorbent Assay, medicine.disease_cause, Drug Administration Schedule, Immunoglobulin G, Young Adult, Nephelometry and Turbidimetry, hemic and lymphatic diseases, intravenous immunoglobulin, Pelvic inflammatory disease, Streptococcus pneumoniae, Humans, Immunologic Factors, Medicine, Infection control, Prospective Studies, Child, Infusions, Intravenous, Immunodeficiency, Aged, pediatric patients, biology, business.industry, Immunologic Deficiency Syndromes, Immunoglobulins, Intravenous, Infant, Middle Aged, medicine.disease, Antibodies, Bacterial, Vaccination, Treatment Outcome, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, Immunology, biology.protein, Primary immunodeficiency, Female, Antibody, seroepidemiology, specific antipneumococcal IgG, business, immunodeficiency, Biomarkers
Abstract

OBJECTIVES:Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization.METHODS:Patients received 7 consecutive IVIG infusions. Total IgG and PnPsAb levels were determined on plasma samples obtained before and after infusion.RESULTS:Twenty-two children with PID were treated with IVIG (mean weekly dose: 0.10 g/kg). The mean trough and peak levels of total IgG were 7.77 and 13.93 g/L, respectively. Trough and peak geometric mean concentrations and distribution curves differed between serotypes and showed wide dispersion (0.17–7.96 µg/mL). In patients (89%–100%), antibodies against most serotypes reached trough levels ≥0.2 µg/mL, a threshold considered protective against invasive pneumococcal infection. For several serotypes, trough levels reached ≥1.0 to 1.3 µg/mL, the level found in adults. Trough geometric mean concentrations correlated well with the PnPsAb contents of the IVIG product.CONCLUSIONS:In IVIG-treated children with PID, protective PnPsAb levels for most pathogenic serotypes were obtained. A correlation was observed between PnPsAb levels in patients and in the IVIG product. This offers the potential to improve infection prevention by adapting the IVIG product and dose according to epidemiology.

Published
2014

4. Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes

Author

Bénédicte Neven, Richard Mouy, Jean-Marc Treluyer, Christophe Bardin, Pierre Quartier, Franz Foissac, Carine Wouters, Sandrine Compeyrot-Lacassagne, Saïk Urien, Brigitte Bader-Meunier, Benoit Florkin, BMC, Ed., CIC-0901, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Pharmacologie, Service d'immuno-hématologie pédiatrique [CHU Necker], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and CHU Cochin [AP-HP]

Subjects
Male, Arthritis, Pharmacology, Gastroenterology, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pharmacology (medical), Tissue Distribution, Prospective Studies, Prospective cohort study, Child, 0303 health sciences, education.field_of_study, Syndrome, 3. Good health, Dose–response relationship, C-Reactive Protein, Treatment Outcome, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Algorithms, medicine.drug, Research Article, musculoskeletal diseases, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, Injections, Subcutaneous, Population, Models, Biological, Drug Administration Schedule, 03 medical and health sciences, Young Adult, Pharmacokinetics, Internal medicine, medicine, Humans, education, 030304 developmental biology, 030203 arthritis & rheumatology, Anakinra, Dose-Response Relationship, Drug, business.industry, Hereditary Autoinflammatory Diseases, Infant, medicine.disease, Systemic-onset juvenile idiopathic arthritis, Arthritis, Juvenile, Interleukin 1 Receptor Antagonist Protein, Pharmacodynamics, business
Abstract

International audience; BACKGROUND: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes. METHODS: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions. The data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix. RESULTS: A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic evaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics. Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities. The final estimates were 6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the CRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline and large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP levels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days CONCLUSIONS: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below.

Published
2013
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5. FAS-L, IL-10, and double-negative CD4-CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function

Author

Olivier Hermine, Capucine Picard, Frédéric Rieux-Laucat, Olivier Lambotte, José Barbot, Eric Solary, Brigitte Bader-Meunier, Jean-Laurent Casanova, Marie-Claude Stolzenberg, Benoit Florkin, Claire Fieschi, Françoise Le Deist, Nicolas Ducrot, Bénédicte Neven, Aude Magerus-Chatinet, Alina Ferster, Marianne Debré, Catherine Schaffner, Alain Fischer, Peter D. Arkwright, Stéphane Blanche, Maria S. Loffredo, Claire Galambrun, Caroline Thomas, Slama, Catherine, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, medicine.disease_cause, Biochemistry, Autoimmunity, 0302 clinical medicine, Child, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Hypergammaglobulinemia, Syndrome, Hematology, Middle Aged, Interleukin-10, 3. Good health, Interleukin 10, Child, Preschool, CD4 Antigens, Adult, Fas Ligand Protein, Adolescent, CD8 Antigens, Immunology, Lymphoproliferative disorders, Biology, Autoimmune Diseases, Young Adult, 03 medical and health sciences, Germline mutation, medicine, Humans, fas Receptor, 030304 developmental biology, Infant, Newborn, Infant, Cell Biology, medicine.disease, Molecular biology, Lymphoproliferative Disorders, Apoptosis, Case-Control Studies, Autoimmune lymphoproliferative syndrome, Mutation, Biomarkers, CD8, 030215 immunology
Abstract

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRαβ+ CD4−CD8− T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.

Published
2009
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6. Clinical features of anti-neutrophil cytoplasmic antibody-associated systemic vasculitis in French children

Author

Jérôme Harambat, Benoit Florkin, H See, Bruno Ranchin, H Flodrops, Pierre Quartier, T Ulinski, AS Sacri, Rémi Salomon, and Stéphane Decramer

Subjects
Pediatrics, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, medicine.medical_treatment, urologic and male genital diseases, Gastroenterology, Rheumatology, Internal medicine, medicine, Immunology and Allergy, Pediatrics, Perinatology, and Child Health, Dialysis, Anti-neutrophil cytoplasmic antibody, Proteinuria, biology, Panca, business.industry, lcsh:RJ1-570, lcsh:Pediatrics, medicine.disease, biology.organism_classification, Transplantation, Poster Presentation, Pediatrics, Perinatology and Child Health, medicine.symptom, lcsh:RC925-935, business, Kidney disease, Systemic vasculitis
Abstract

Results Forty-seven children were included, 15 (32%) with WG and 32 (68%) with MPA, 77% children were pANCA +/MPO. Female predominated (85%), the median age at diagnosis was 10 years (2-16), and average time to diagnosis was 8 months (0-58). 53% children presented with fever, 77% with deterioration of general condition. 91% had renal involvement. Among them 91% had proteinuria, 44% had hypertension, 79% had renal failure of whom one third presented with end-stage renal disease (ESRD), 22% had gross hematuria and 82% microscopic hematuria. Half the patients showed pulmonary involvement (alveolar hemorrhage for 77% and nodules for 18%). 28% presented with upper airways involvement, 38% with cutaneous lesions (67% purpura), and 19% with arthritis. Few had digestive, ophthalmic or CNS involvement. After an average follow-up of 5 years (2m24y), 3 patients (6%) died. 60% were considered in remission (partial or total) after induction treatment and 77% at last follow-up. 33% of children with initial renal involvement developed chronic kidney disease, half of them progressed to ESRD. 43% needed dialysis and 29% underwent a renal transplantation.

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