Author: "Casanova Jean-Laurent" / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

116 results on '"Casanova Jean-Laurent"'

1. Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.

Author: Casanova, Jean-Laurent, Casanova, Jean-Laurent, Tree, Timothy, Oram, Richard, Johnson, Matthew, Ogishi, Masato, Domingo-Vila, Clara, De Franco, Elisa, Wakeling, Matthew, Imane, Zineb, Resnick, Brittany, Williams, Evangelia, Galão, Rui, Caswell, Richard, Russ-Silsby, James, Seeleuthner, Yoann, Rinchai, Darawan, Fagniez, Iris, Benson, Basilin, Dufort, Matthew, Speake, Cate, Smithmyer, Megan, Hudson, Michelle, Dobbs, Rebecca, Hattersley, Andrew, Zhang, Peng, Boisson-Dupuis, Stephanie, Anderson, Mark, Quandt, Zoe, Casanova, Jean-Laurent, Casanova, Jean-Laurent, Tree, Timothy, Oram, Richard, Johnson, Matthew, Ogishi, Masato, Domingo-Vila, Clara, De Franco, Elisa, Wakeling, Matthew, Imane, Zineb, Resnick, Brittany, Williams, Evangelia, Galão, Rui, Caswell, Richard, Russ-Silsby, James, Seeleuthner, Yoann, Rinchai, Darawan, Fagniez, Iris, Benson, Basilin, Dufort, Matthew, Speake, Cate, Smithmyer, Megan, Hudson, Michelle, Dobbs, Rebecca, Hattersley, Andrew, Zhang, Peng, Boisson-Dupuis, Stephanie, Anderson, Mark, and Quandt, Zoe
Abstract: We previously reported two siblings with inherited PD-1 deficiency who died from autoimmune pneumonitis at 3 and 11 years of age after developing other autoimmune manifestations, including type 1 diabetes (T1D). We report here two siblings, aged 10 and 11 years, with neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk), who are homozygous for a splice-site variant of CD274 (encoding PD-L1). This variant results in the exclusive expression of an alternative, loss-of-function PD-L1 protein isoform in overexpression experiments and in the patients primary leukocytes. Surprisingly, cytometric immunophenotyping and single-cell RNA sequencing analysis on blood leukocytes showed largely normal development and transcriptional profiles across lymphoid and myeloid subsets in the PD-L1-deficient siblings, contrasting with the extensive dysregulation of both lymphoid and myeloid leukocyte compartments in PD-1 deficiency. Our findings suggest that PD-1 and PD-L1 are essential for preventing early-onset T1D but that, unlike PD-1 deficiency, PD-L1 deficiency does not lead to fatal autoimmunity with extensive leukocytic dysregulation.
Published: 2024

2. SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Author: Chan, Yi-Hao, Chan, Yi-Hao, Lundberg, Vanja, Le Pen, Jérémie, Yuan, Jiayi, Lee, Danyel, Pinci, Francesca, Volpi, Stefano, Nakajima, Koji, Bondet, Vincent, Åkesson, Sanna, Khobrekar, Noopur, Bodansky, Aaron, Du, Likun, Melander, Tina, Mariaggi, Alice-Andrée, Seeleuthner, Yoann, Saleh, Tariq, Chakravarty, Debanjana, Marits, Per, Dobbs, Kerry, Vonlanthen, Sofie, Hennings, Viktoria, Thörn, Karolina, Rinchai, Darawan, Bizien, Lucy, Chaldebas, Matthieu, Sobh, Ali, Özçelik, Tayfun, Keles, Sevgi, AlKhater, Suzan, Prando, Carolina, Meyts, Isabelle, Wilson, Michael, Rosain, Jérémie, Jouanguy, Emmanuelle, Aubart, Mélodie, Abel, Laurent, Mogensen, Trine, Pan-Hammarström, Qiang, Gao, Daxing, Duffy, Darragh, Cobat, Aurélie, Berg, Stefan, Notarangelo, Luigi, Harschnitz, Oliver, Rice, Charles, Studer, Lorenz, Casanova, Jean-Laurent, Ekwall, Olov, Zhang, Shen-Ying, Chan, Yi-Hao, Chan, Yi-Hao, Lundberg, Vanja, Le Pen, Jérémie, Yuan, Jiayi, Lee, Danyel, Pinci, Francesca, Volpi, Stefano, Nakajima, Koji, Bondet, Vincent, Åkesson, Sanna, Khobrekar, Noopur, Bodansky, Aaron, Du, Likun, Melander, Tina, Mariaggi, Alice-Andrée, Seeleuthner, Yoann, Saleh, Tariq, Chakravarty, Debanjana, Marits, Per, Dobbs, Kerry, Vonlanthen, Sofie, Hennings, Viktoria, Thörn, Karolina, Rinchai, Darawan, Bizien, Lucy, Chaldebas, Matthieu, Sobh, Ali, Özçelik, Tayfun, Keles, Sevgi, AlKhater, Suzan, Prando, Carolina, Meyts, Isabelle, Wilson, Michael, Rosain, Jérémie, Jouanguy, Emmanuelle, Aubart, Mélodie, Abel, Laurent, Mogensen, Trine, Pan-Hammarström, Qiang, Gao, Daxing, Duffy, Darragh, Cobat, Aurélie, Berg, Stefan, Notarangelo, Luigi, Harschnitz, Oliver, Rice, Charles, Studer, Lorenz, Casanova, Jean-Laurent, Ekwall, Olov, and Zhang, Shen-Ying
Abstract: Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.
Published: 2024

3. Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs.

Author: Casanova, Jean-Laurent, Casanova, Jean-Laurent, Anderson, Mark S, Casanova, Jean-Laurent, Casanova, Jean-Laurent, and Anderson, Mark S
Abstract: Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing type I IFNs due to rare inborn errors of autoimmune regulator (AIRE)-driven T cell tolerance were discovered in 2006, but not initially linked to any viral disease. These two lines of clinical investigation converged in 2020, with the discovery that inherited and/or autoimmune deficiencies of type I IFN immunity accounted for approximately 15%-20% of cases of critical COVID-19 pneumonia in unvaccinated individuals. Thus, insufficient type I IFN immunity at the onset of SARS-CoV-2 infection may be a general determinant of life-threatening COVID-19. These findings illustrate the unpredictable, but considerable, contribution of the study of rare human genetic diseases to basic biology and public health.
Published: 2023

4. Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.

Author: García-García, Ana, García-García, Ana, Pérez de Diego, Rebeca, Flores, Carlos, Rinchai, Darawan, Solé-Violán, Jordi, Deyà-Martínez, Àngela, García-Solis, Blanca, Lorenzo-Salazar, José, Hernández-Brito, Elisa, Lanz, Anna-Lisa, Moens, Leen, Bucciol, Giorgia, Almuqamam, Mohamed, Domachowske, Joseph, Colino, Elena, Santos-Perez, Juan, Marco, Francisco, Pignata, Claudio, Bousfiha, Aziz, Turvey, Stuart, Bauer, Stefanie, Haerynck, Filomeen, Ocejo-Vinyals, Javier, Lendinez, Francisco, Prader, Seraina, Naumann-Bartsch, Nora, Pachlopnik Schmid, Jana, Biggs, Catherine, Hildebrand, Kyla, Dreesman, Alexandra, Cárdenes, Miguel, Ailal, Fatima, Benhsaien, Ibtihal, Giardino, Giuliana, Molina-Fuentes, Agueda, Fortuny, Claudia, Madhavarapu, Swetha, Conway, Daniel, Prando, Carolina, Schidlowski, Laire, Martínez de Saavedra Álvarez, María, Alfaro, Rafael, Rodríguez de Castro, Felipe, Meyts, Isabelle, Hauck, Fabian, Puel, Anne, Bastard, Paul, Boisson, Bertrand, Jouanguy, Emmanuelle, Abel, Laurent, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Alsina, Laia, Rodríguez-Gallego, Carlos, García-García, Ana, García-García, Ana, Pérez de Diego, Rebeca, Flores, Carlos, Rinchai, Darawan, Solé-Violán, Jordi, Deyà-Martínez, Àngela, García-Solis, Blanca, Lorenzo-Salazar, José, Hernández-Brito, Elisa, Lanz, Anna-Lisa, Moens, Leen, Bucciol, Giorgia, Almuqamam, Mohamed, Domachowske, Joseph, Colino, Elena, Santos-Perez, Juan, Marco, Francisco, Pignata, Claudio, Bousfiha, Aziz, Turvey, Stuart, Bauer, Stefanie, Haerynck, Filomeen, Ocejo-Vinyals, Javier, Lendinez, Francisco, Prader, Seraina, Naumann-Bartsch, Nora, Pachlopnik Schmid, Jana, Biggs, Catherine, Hildebrand, Kyla, Dreesman, Alexandra, Cárdenes, Miguel, Ailal, Fatima, Benhsaien, Ibtihal, Giardino, Giuliana, Molina-Fuentes, Agueda, Fortuny, Claudia, Madhavarapu, Swetha, Conway, Daniel, Prando, Carolina, Schidlowski, Laire, Martínez de Saavedra Álvarez, María, Alfaro, Rafael, Rodríguez de Castro, Felipe, Meyts, Isabelle, Hauck, Fabian, Puel, Anne, Bastard, Paul, Boisson, Bertrand, Jouanguy, Emmanuelle, Abel, Laurent, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Alsina, Laia, and Rodríguez-Gallego, Carlos
Abstract: X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
Published: 2023

5. A second update on mapping the human genetic architecture of COVID-19

Author: Kanai, M, Andrews, S, Cordioli, M, Stevens, C, Neale, B, Daly, M, Ganna, A, Pathak, G, Iwasaki, A, Karjalainen, J, Mehtonen, J, Pirinen, M, Chwialkowska, K, Trankiem, A, Balaconis, M, Veerapen, K, Wolford, B, Ahmad, H, von Hohenstaufen Puoti, K, Boer, C, Boua, P, Butler-Laporte, G, Cadilla, C, Chwiałkowska, K, Colombo, F, Douillard, V, Dueker, N, Dutta, A, El-Sherbiny, Y, Eltoukhy, M, Esmaeeli, S, Faucon, A, Fave, M, Cadenas, I, Francescatto, M, Francioli, L, Franke, L, Fuentes, M, Durán, R, Cabrero, D, Harry, E, Jansen, P, Szentpéteri, J, Kaja, E, Kirk, C, Kousathanas, A, Krieger, J, Patel, S, Lemaçon, A, Limou, S, Lió, P, Marouli, E, Marttila, M, Medina-Gómez, C, Michaeli, Y, Migeotte, I, Mondal, S, Moreno-Estrada, A, Moya, L, Nakanishi, T, Nasir, J, Pasko, D, Pearson, N, Pereira, A, Priest, J, Prijatelj, V, Prokić, I, Teumer, A, Várnai, R, Romero-Gómez, M, Roos, C, Rosenfeld, J, Ruolin, L, Schulte, E, Schurmann, C, Sedaghati-khayat, B, Shaheen, D, Shivanathan, I, Sipeky, C, Sirui, Z, Striano, P, Tanigawa, Y, Remesal, A, Vadgama, N, Vallerga, C, van der Laan, S, Verdugo, R, Wang, Q, Wei, Z, Zainulabid, U, Zárate, R, Auton, A, Shelton, J, Shastri, A, Weldon, C, Filshtein-Sonmez, T, Coker, D, Symons, A, Aslibekyan, S, O’Connell, J, Ye, C, Hatoum, A, Agrawal, A, Bogdan, R, Colbert, S, Thompson, W, Fan, C, Johnson, E, Niazyan, L, Davidyants, M, Arakelyan, A, Avetyan, D, Bekbossynova, M, Tauekelova, A, Tuleutayev, M, Sailybayeva, A, Ramankulov, Y, Zholdybayeva, E, Dzharmukhanov, J, Kassymbek, K, Tsechoeva, T, Turebayeva, G, Smagulova, Z, Muratov, T, Khamitov, S, Kwong, A, Timpson, N, Niemi, M, Rahmouni, S, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Georges, M, Moutschen, M, Misset, B, Darcis, G, Gofflot, S, Bouysran, Y, Busson, A, Peyrassol, X, Wilkin, F, Pichon, B, Smits, G, Vandernoot, I, Goffard, J, Tiembe, N, Morrison, D, Afilalo, J, Mooser, V, Richards, J, Rousseau, S, Durand, M, Forgetta, V, Laurent, L, Afrasiabi, Z, Bouab, M, Tselios, C, Xue, X, Afilalo, M, Oliveira, M, St-Cyr, J, Boisclair, A, Ragoussis, J, Auld, D, Kaufmann, D, Lathrop, G, Bourque, G, Décary, S, Falcone, E, Montpetit, A, Piché, A, Renoux, C, Tremblay, K, Tse, S, Zawati, M, Davis, L, Cox, N, Below, J, Sealock, J, Shuey, M, Polikowsky, H, Petty, L, Shaw, D, Chen, H, Zhu, W, Schmidt, A, Ludwig, K, Maj, C, Rolker, S, Balla, D, Behzad, P, Nöthen, M, Fazaal, J, Keitel, V, Jensen, B, Feldt, T, Marx, N, Dreher, M, Pink, I, Cornberg, M, Illig, T, Lehmann, C, Schommers, P, Rybniker, J, Augustin, M, Knopp, L, Kurth, I, Eggermann, T, Volland, S, Berger, M, Brenner, T, Hinney, A, Witzke, O, Konik, M, Bals, R, Herr, C, Ludwig, N, Walter, J, Latz, E, Schmidt, S, Brooks, J, Bull, S, Elliott, L, Gagnon, F, Greenwood, C, Hung, R, Lawless, J, Paterson, A, Sun, L, Rauh, M, Briollais, L, Gingras, A, Bombard, Y, Pugh, T, Simpson, J, Goneau, L, Halevy, A, Maslove, D, Borgundvaag, B, Devine, L, Bearss, E, Richardson, D, Arnoldo, S, Friedman, S, Taher, A, Stern, S, Dagher, M, Vasilevska-Ristovska, J, Biggs, C, Mickiewicz, B, Strug, L, Scherer, S, Aziz, N, Jones, S, Knoppers, B, Lathrop, M, Turvey, S, Yeung, R, Allen, U, Cheung, A, Herridge, M, Hunt, M, Lerner-Ellis, J, Taher, J, Parekh, R, Hiraki, L, Cowan, J, Ducharme, F, Ostrowski, M, Bernier, F, Kellner, J, Garg, E, Yoo, S, Vlasschaert, C, Frangione, E, Chung, M, Noor, A, Greenfeld, E, Colwill, K, Clausen, M, Chao, G, Yue, F, Fritzler, M, Whitney, J, Thiruvahindrapuram, B, Garant, J, Abraham, R, Davis, A, Campigotto, A, Papenburg, J, Niranjan, K, Betschel, S, Sadarangani, M, Barton-Forbes, M, Hanley, M, Fung, C, Lapadula, E, Macdonald, G, Puopolo, M, Kaushik, D, Nirmalanathan, K, Wong, I, Khan, Z, Zarei, N, Michalowska, M, Modi, B, Persia, P, Estacio, A, Buchholz, M, Cheatley, P, Lorenti, M, Aman, N, Matveev, V, Budylowski, P, Upton, J, Morris, S, Boyd, T, Chowdhary, S, Casalino, S, Morgan, G, Mighton, C, Mcgeer, A, Mazzulli, T, Mcleod, S, Binnie, A, Faghfoury, H, Chertkow, H, Racher, H, Serbanescu, M, Pavenski, K, Esser, M, Thompson, G, Herbrick, J, Gignoux, C, Wicks, S, Crooks, K, Barnes, K, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Schulze, T, Heilbronner, U, Papiol, S, Corbetta, A, Wendtner, C, Spinner, C, Erber, J, Schneider, J, Winter, C, Wiltfang, J, Budde, M, Senner, F, Kalman, J, Protzer, U, Mueller, N, Mousas, A, Liontos, A, Christaki, E, Milionis, H, Tsilidis, K, Asimakopoulos, A, Kanellopoulou, A, Markozannes, G, Biros, D, Milionis, O, Tsourlos, S, Athanasiou, L, Kolios, N, Pappa, C, Papathanasiou, A, Pargana, E, Nasiou, M, Kosmidou, M, Rapti, I, Ntotsikas, E, Chaliasos, K, Ntzani, E, Evangelou, E, Gartzonika, K, Georgiou, I, Tzoulaki, I, Ellinghaus, D, Degenhardt, F, Cáceres, M, Juzenas, S, Lenz, T, Albillos, A, Julià, A, Prati, D, Solligård, E, Garcia, F, Tran, F, Hanses, F, Baselli, G, Zoller, H, Holter, J, Fernández, J, Barretina, J, Valenti, L, Bujanda, L, Buti, M, D’Amato, M, Banales, J, Rosenstiel, P, Koehler, P, Invernizzi, P, de Cid, R, Asselta, R, Schreiber, S, Duga, S, Hehr, U, Franke, A, Maya-Miles, D, Hov, J, Karlsen, T, Folseraas, T, Teles, A, Tanck, A, Gassner, C, Azuure, C, Wacker, E, Uellendahl-Werth, F, Hemmrich-Stanisak, G, Elabd, H, Kässens, J, Arora, J, Lerga-Jaso, J, Wienbrandt, L, Rühlemann, M, Wendorff, M, Figuera Basso, M, Vadla, M, Wittig, M, Braun, N, Lenning, O, Özer, O, Myhre, R, Raychaudhuri, S, Wesse, T, Albrecht, W, Yi, X, Ortiz, A, de Salazar, A, Chercoles, A, Palom, A, Ruiz, A, Garcia-Fernandez, A, Blanco-Grau, A, Mantovani, A, Holten, A, Bandera, A, Cherubini, A, Protti, A, Aghemo, A, Gerussi, A, Ramirez, A, Nebel, A, Barreira, A, Lleo, A, Kildal, A, Biondi, A, Caballero-Garralda, A, Gori, A, Glück, A, Lind, A, Nolla, A, Latiano, A, Fracanzani, A, Peschuck, A, Cavallero, A, Dyrhol-Riise, A, Ruello, A, Muscatello, A, Voza, A, Rando-Segura, A, Solier, A, Cortes, B, Mateos, B, Nafria-Jimenez, B, Schaefer, B, Bellinghausen, C, Ferrando, C, de la Horra, C, Quereda, C, Scollo, C, Lange, C, Hu, C, Paccapelo, C, Angelini, C, Cappadona, C, Bianco, C, Cea, C, Sancho, C, Hoff, D, Galimberti, D, Haschka, D, Jiménez, D, Pestaña, D, Toapanta, D, Muñiz-Diaz, E, Azzolini, E, Sandoval, E, Binatti, E, Scarpini, E, Casalone, E, Urrechaga, E, Paraboschi, E, Pontali, E, Reverter, E, Calderón, E, Navas, E, Contro, E, Arana-Arri, E, Aziz, F, Sánchez, F, Ceriotti, F, Martinelli-Boneschi, F, Peyvandi, F, Blasi, F, Malvestiti, F, Medrano, F, Mesonero, F, Rodriguez-Frias, F, Müller, F, Bellani, G, Pesenti, A, Zanella, A, Grasselli, G, Pezzoli, G, Costantino, G, Albano, G, Cardamone, G, Bellelli, G, Citerio, G, Foti, G, Lamorte, G, Matullo, G, Kurihara, H, Neb, H, My, I, Hernández, I, de Rojas, I, Galván-Femenia, I, Afset, J, Heyckendorf, J, Damås, J, Ampuero, J, Martín, J, Erdmann, J, Badia, J, Dopazo, J, Bergan, J, Quero, J, Goikoetxea, J, Delgado, J, Guerrero, J, Risnes, K, Banasik, K, Müller, K, Gaede, K, Garcia-Etxebarria, K, Tonby, K, Heggelund, L, Bettini, L, Sumoy, L, Terranova, L, Gustad, L, Garbarino, L, Santoro, L, Téllez, L, Roade, L, Ostadreza, M, Intxausti, M, Kogevinas, M, Riveiro-Barciela, M, Schaefer, M, Gutiérrez-Stampa, M, Carrabba, M, Valsecchi, M, Hernandez-Tejero, M, Vehreschild, M, Manunta, M, Acosta-Herrera, M, D’Angiò, M, Baldini, M, Cazzaniga, M, Marquié, M, Castoldi, M, Cecconi, M, Tomasi, M, Boada, M, Joannidis, M, Mazzocco, M, Ciccarelli, M, Rodríguez-Gandía, M, Bocciolone, M, Miozzo, M, Ayo, N, Blay, N, Chueca, N, Montano, N, Martínez, N, Cornely, O, Palmieri, O, Faverio, P, Preatoni, P, Bonfanti, P, Omodei, P, Tentorio, P, Castro, P, Rodrigues, P, Izquierdo-Sanchez, L, España, P, Hoffmann, P, Bacher, P, de Pablo, R, Ferrer, R, Gualtierotti, R, Gallego-Durán, R, Nieto, R, Carpani, R, Morilla, R, Badalamenti, S, Haider, S, Ciesek, S, Bombace, S, Marsal, S, Klein, S, Pelusi, S, Wilfling, S, Goerg, S, Bosari, S, Brunak, S, Heilmann-Heimbach, S, Aliberti, S, Dudman, S, Zheng, T, Bahmer, T, Pumarola, T, Cejudo, T, Rimoldi, V, Monzani, V, Skogen, V, Friaza, V, Andrade, V, Moreno, V, Peter, W, Farre, X, Khodamoradi, Y, Grimsrud, M, May, S, Colombo, A, Virginia, M, Dorador, C, Fuentes-Guajardo, M, Silva, A, Espinosa-Parrilla, Y, Yáñez, C, Retamales-Ortega, R, Saez Hidalgo, J, Tobar-Calfucoy, E, Carvajal-Silva, L, Martínez, M, Cerpa, L, Christian, M, Cappelli, C, Valenzuela-Jorquera, H, Zapata-Contreras, D, Zuñiga-Pacheco, P, Nova-Lamperti, E, Sanhueza, S, Donoso, G, Bocchieri, P, Kochifas, P, Quiñones, L, Pedersen, O, Geller, F, Westergaard, D, Sequeros, C, Nissen, J, Nielsen, S, Feldt-Rasmussen, U, Bliddal, S, Grønbæk, K, Ullum, H, Ostrowski, S, Feenstra, B, Shahin, D, Sobh, A, Shoma, A, Nkambul, L, Elhadidy, T, Abd Elghafar, M, El-Jawhari, J, Mohamed, A, Elnagdy, M, Samir, A, Abdel-Aziz, M, Khafaga, W, El-Lawaty, W, Torky, M, El-Shanshory, M, Elzeiny, A, Rashad, A, Mansour, T, Yassen, A, Hegazy, M, Okasha, K, Eid, M, Hanteera, M, Medina-Gomez, C, Ikram, M, Uitterlinden, A, Ripatti, S, Jermy, B, 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Csilla, Sirui, Zhou, Striano, Pasquale, Tanigawa, Yosuke, Remesal, Alicia Utrilla, Vadgama, Nirmal, Vallerga, Costanza L., van der Laan, Sander, Verdugo, Ricardo A., Wang, Qingbo S., Wei, Zhou, Zainulabid, Ummu Afeera, Zárate, Ruth N., Auton, Adam, Shelton, Janie F., Shastri, Anjali J., Weldon, Catherine H., Filshtein-Sonmez, Teresa, Coker, Daniella, Symons, Antony, Aslibekyan, Stella, O’Connell, Jared, Ye, Chelsea, Hatoum, Alexander S., Agrawal, Arpana, Bogdan, Ryan, Colbert, Sarah M. C., Thompson, Wesley K., Fan, Chun Chieh, Johnson, Emma C., Niazyan, Lyudmila, Davidyants, Mher, Arakelyan, Arsen, Avetyan, Diana, Bekbossynova, Makhabbat, Tauekelova, Ainur, Tuleutayev, Mukhtar, Sailybayeva, Aliya, Ramankulov, Yerlan, Zholdybayeva, Elena, Dzharmukhanov, Jarkyn, Kassymbek, Kuat, Tsechoeva, Tatyana, Turebayeva, Gulsimzhan, Smagulova, Zauresh, Muratov, Timur, Khamitov, Sadyk, Kwong, Alex S. F., Timpson, Nicholas J., Niemi, Mari E. K., Rahmouni, Souad, Guntz, Julien, Beguin, Yves, Pigazzini, Sara, Nkambule, Lindokuhle, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gilles, Gofflot, Stéphanie, Bouysran, Youssef, Busson, Adeline, Peyrassol, Xavier, Wilkin, Françoise, Pichon, Bruno, Smits, Guillaume, Vandernoot, Isabelle, Goffard, Jean-Christophe, Tiembe, Nicky, Morrison, David R., Afilalo, Jonathan, Mooser, Vincent, Richards, J. Brent, Rousseau, Simon, Durand, Madeleine, Forgetta, Vincenzo, Laurent, Laetitia, Afrasiabi, Zaman, Bouab, Meriem, Tselios, Chris, Xue, Xiaoqing, Afilalo, Marc, Oliveira, Maureen, St-Cyr, Janick, Boisclair, Ariane, Ragoussis, Jiannis, Auld, Daniel, Kaufmann, Daniel E., Lathrop, G. Mark, Bourque, Guillaume, Décary, Simon, Falcone, Emilia Liana, Montpetit, Alexandre, Piché, Alain, Renoux, Christel, Tremblay, Karine, Tse, Sze Man, Zawati, Ma’n H., Davis, Lea K., Cox, Nancy J., Below, Jennifer E., Sealock, Julia M., Faucon, Annika B., Shuey, Megan M., Polikowsky, Hannah G., Petty, Lauren E., Shaw, Douglas M., Chen, Hung-Hsin, Zhu, Wanying, Schmidt, Axel, Ludwig, Kerstin U., Maj, Carlo, Rolker, Selina, Balla, Daniella, Behzad, Pari, Nöthen, Markus M., Fazaal, Julia, Keitel, Verena, Jensen, Björn-Erik Ole, Feldt, Torsten, Marx, Nikolaus, Dreher, Michael, Pink, Isabell, Cornberg, Markus, Illig, Thomas, Lehmann, Clara, Schommers, Philipp, Rybniker, Jan, Augustin, Max, Knopp, Lisa, Kurth, Ingo, Eggermann, Thomas, Volland, Sonja, Berger, Marc M., Brenner, Thorsten, Hinney, Anke, Witzke, Oliver, Konik, Margarethe J., Bals, Robert, Herr, Christian, Ludwig, Nicole, Walter, Jörn, Latz, Eicke, Schmidt, Susanne V., Brooks, Jennifer D., Bull, Shelley, Elliott, Lloyd T., Gagnon, France, Greenwood, Celia M. T., Hung, Rayjean J., Lawless, Jerry F., Paterson, Andrew D., Sun, Lei, Rauh, Michael, Briollais, Laurent, Gingras, Anne-Claude, Bombard, Yvonne, Pugh, Trevor J., Simpson, Jared, Goneau, Lee W., Halevy, Anat R., Maslove, David M., Borgundvaag, Bjug, Devine, Luke, Bearss, Erin, Richardson, David, Arnoldo, Saranya, Friedman, Steven Marc, Taher, Ahmed, Stern, Seth, Dagher, Marc, Vasilevska-Ristovska, Jovanka, Biggs, Catherine M., Mickiewicz, Beata, Strug, Lisa J., Scherer, Stephen W., Aziz, Naveed, Jones, Steven J. M., Knoppers, Bartha M., Lathrop, Mark, Turvey, Stuart E., Yeung, Rae S. M., Allen, Upton, Cheung, Angela M., Herridge, Margaret S., Hunt, Miranda, Lerner-Ellis, Jordan, Taher, Jennifer, Parekh, Rulan S., Hiraki, Linda T., Cowan, Juthaporn, Ducharme, Francine M., Ostrowski, Mario, Bernier, Francois P., Kellner, Jim, Garg, Elika, Yoo, Samantha, Vlasschaert, Caitlyn, Frangione, Erika, Chung, Monica, Noor, Abdul, Greenfeld, Elena, Colwill, Karen, Clausen, Marc, Chao, Gary, Yue, FengYun, Fritzler, Marvin, Whitney, Joseph, Thiruvahindrapuram, Bhooma, Garant, Jean-Michel, Abraham, Rohan, Davis, Adrienne, Campigotto, Aaron, Papenburg, Jesse, Niranjan, Kissoon, Betschel, Stephen, Sadarangani, Manish, Barton-Forbes, Michelle, Hanley, Michaela, Fung, Chun Yiu Jordan, Lapadula, Elisa, MacDonald, Georgia, Puopolo, Michael, Kaushik, Deepanjali, Nirmalanathan, Konika, Wong, Iris, Khan, Zeeshan, Zarei, Natasha, Michalowska, Maria, Modi, Bhavi P., Persia, Pourshahnazari, Estacio, Antonio, Buchholz, Megan, Cheatley, Patti Lou, Lorenti, Miranda, Aman, Nowrin F., Matveev, Vitaliy, Budylowski, Patrick, Upton, Julia, Morris, Shaun, Boyd, Tracy, Chowdhary, Sunakshi, Casalino, Selina, Morgan, Gregory, Mighton, Chloe, McGeer, Allison, Mazzulli, Tony, McLeod, Shelley L., Binnie, Alexandra, Faghfoury, Hanna, Chertkow, Howard, Racher, Hilary, Serbanescu, Mihaela A., Pavenski, Katerina, Esser, Michael, Thompson, Graham, Herbrick, Jo-Anne, Gignoux, Christopher R., Wicks, Stephen J., Crooks, Kristy, Barnes, Kathleen C., Daya, Michelle, Shortt, Jonathan, Rafaels, Nicholas, Chavan, Sameer, Schulze, Thomas G., Heilbronner, Urs, Papiol, Sergi, Corbetta, Andrea, Wendtner, Clemens M., Spinner, Christoph D., Erber, Johanna, Schneider, Jochen, Winter, Christof, Wiltfang, Jens, Budde, Monika, Senner, Fanny, Kalman, Janos L., Protzer, Ulrike, Mueller, Nikola S., Mousas, Abdou, Liontos, Angelos, Christaki, Eirini, Milionis, Haralampos, Tsilidis, Konstantinos, Asimakopoulos, Alexandros, Kanellopoulou, Afroditi, Markozannes, Georgios, Biros, Dimitrios, Milionis, Orestis, Tsourlos, Stavros, Athanasiou, Lazaros, Kolios, Nikolaos-Gavriil, Pappa, Christiana, Papathanasiou, Alexandros, Pargana, Eleni, Nasiou, Maria, Kosmidou, Maria, Rapti, Iro, Ntotsikas, Evangelos, Chaliasos, Konstantinos, Ntzani, Evangelia, Evangelou, Evangelos, Gartzonika, Konstantina, Georgiou, Ioannis, Tzoulaki, Ioanna, Ellinghaus, David, Degenhardt, Frauke, Cáceres, Mario, Juzenas, Simonas, Lenz, Tobias L., Albillos, Agustín, Julià, Antonio, Prati, Daniele, Solligård, Erik, Garcia, Federico, Tran, Florian, Hanses, Frank, Baselli, Guido, Zoller, Heinz, Holter, Jan Cato, Fernández, Javier, Barretina, Jordi, Valenti, Luca, Bujanda, Luis, Buti, Maria, D’Amato, Mauro, Banales, Jesus M., Rosenstiel, Philip, Koehler, Philipp, Invernizzi, Pietro, de Cid, Rafael, Asselta, Rosanna, Schreiber, Stefan, Duga, Stefano, Hehr, Ute, Franke, Andre, Maya-Miles, Douglas, Hov, Johannes R., Karlsen, Tom H., Folseraas, Trine, Teles, Ana, Tanck, Anja, Gassner, Christoph, Azuure, Clinton, Wacker, Eike Matthias, Uellendahl-Werth, Florian, Hemmrich-Stanisak, Georg, ElAbd, Hesham, Kässens, Jan, Arora, Jatin, Lerga-Jaso, Jon, Wienbrandt, Lars, Rühlemann, Malte Christoph, Wendorff, Mareike, Figuera Basso, Maria E., Vadla, May Sissel, Wittig, Michael, Braun, Nicole, Lenning, Ole Bernt, Özer, Onur, Myhre, Ronny, Raychaudhuri, Soumya, Wesse, Tanja, Albrecht, Wolfgang, Yi, Xiaoli, Ortiz, Aaron Blandino, de Salazar, Adolfo, Chercoles, Adolfo Garrido, Palom, Adriana, Ruiz, Agustín, Garcia-Fernandez, Alba-Estela, Blanco-Grau, Albert, Mantovani, Alberto, Holten, Aleksander Rygh, Bandera, Alessandra, Cherubini, Alessandro, Protti, Alessandro, Aghemo, Alessio, Gerussi, Alessio, Ramirez, Alfredo, Nebel, Almut, Barreira, Ana, Lleo, Ana, Kildal, Anders Benjamin, Biondi, Andrea, Caballero-Garralda, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Nolla, Anna Carreras, Latiano, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Muscatello, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier, Aurora, Cortes, Beatriz, Mateos, Beatriz, Nafria-Jimenez, Beatriz, Schaefer, Benedikt, Bellinghausen, Carla, Ferrando, Carlos, de la Horra, Carmen, Quereda, Carmen, Scollo, Chiara, Lange, Christoph, Hu, Cinzia, Paccapelo, Cinzia, Angelini, Claudio, Cappadona, Claudio, Bianco, Cristiana, Cea, Cristina, Sancho, Cristina, Hoff, Dag Arne Lihaug, Galimberti, Daniela, Haschka, David, Jiménez, David, Pestaña, David, Toapanta, David, Muñiz-Diaz, Eduardo, Azzolini, Elena, Sandoval, Elena, Binatti, Eleonora, Scarpini, Elio, Casalone, Elisabetta, Urrechaga, Eloisa, Paraboschi, Elvezia Maria, Pontali, Emanuele, Reverter, Enric, Calderón, Enrique J., Navas, Enrique, Contro, Ernesto, Arana-Arri, Eunate, Aziz, Fátima, Sánchez, Félix García, Ceriotti, Ferruccio, Martinelli-Boneschi, Filippo, Peyvandi, Flora, Blasi, Francesco, Malvestiti, Francesco, Medrano, Francisco J., Mesonero, Francisco, Rodriguez-Frias, Francisco, Müller, 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Carrabba, Maria, Valsecchi, Maria G., Hernandez-Tejero, María, Vehreschild, Maria J. G. T., Manunta, Maria, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Marquié, Marta, Castoldi, Massimo, Cecconi, Maurizio, Tomasi, Melissa, Boada, Mercè, Joannidis, Michael, Mazzocco, Michela, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Miozzo, Monica, Ayo, Natale Imaz, Blay, Natalia, Chueca, Natalia, Montano, Nicola, Martínez, Nilda, Cornely, Oliver A., Palmieri, Orazio, Faverio, Paola, Preatoni, Paoletta, Bonfanti, Paolo, Omodei, Paolo, Tentorio, Paolo, Castro, Pedro, Rodrigues, Pedro M., Izquierdo-Sanchez, Laura, España, Pedro Pablo, Hoffmann, Per, Bacher, Petra, de Pablo, Raúl, Ferrer, Ricard, Gualtierotti, Roberta, Gallego-Durán, Rocío, Nieto, Rosa, Carpani, Rossana, Morilla, Rubén, Badalamenti, Salvatore, Haider, Sammra, Ciesek, Sandra, Bombace, Sara, Marsal, Sara, Klein, Sebastian, Pelusi, Serena, Wilfling, Sibylle, Goerg, Siegfried, Bosari, Silvano, Brunak, Søren, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Dudman, Susanne, Zheng, Tenghao, Bahmer, Thomas, Pumarola, Tomas, Cejudo, Trinidad Gonzalez, Rimoldi, Valeria, Monzani, Valter, Skogen, Vegard, Friaza, Vicente, Andrade, Victor, Moreno, Victor, Peter, Wolfgang, Farre, Xavier, Khodamoradi, Yascha, Grimsrud, Marit M., May, Sandra, Colombo, Alicia, Virginia, Monardes-Ramírez A., Dorador, Cristina, Fuentes-Guajardo, Macarena, Silva, Andrea X., Espinosa-Parrilla, Yolanda, Yáñez, Cristian E., Retamales-Ortega, Rocío M., Saez Hidalgo, Juan M., Tobar-Calfucoy, Eduardo A., Carvajal-Silva, Laura, Martínez, Matías F., Cerpa, Leslie C., Christian, Muñoz A., Cappelli, Claudio, Valenzuela-Jorquera, Hector, Zapata-Contreras, Daniela, Zuñiga-Pacheco, Paula, Nova-Lamperti, Estefania A., Sanhueza, Sergio A., Donoso, Gerardo, Bocchieri, Pamela, Kochifas, Pia, Quiñones, Luis A., Pedersen, Ole Birger, Geller, Frank, Westergaard, David, Sequeros, Celia Burgos, Nissen, Janna, Nielsen, Susanne Dam, Feldt-Rasmussen, Ulla, Bliddal, Sofie, Grønbæk, Kirsten, Ullum, Henrik, Ostrowski, Sisse Rye, Feenstra, Bjarke, Shahin, Doaa, Sobh, Ali, Shoma, Ashraf, Nkambul, Lindokuhle, Elhadidy, Tamer A., Abd Elghafar, Mohamed S., El-Jawhari, Jehan J., Mohamed, Attia A. S., Elnagdy, Marwa H., Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T., El-Lawaty, Walaa M., Torky, Mohamed S., El-Shanshory, Mohamed R., Elzeiny, Ahmed, Rashad, Amal, Mansour, Tamer A., Yassen, Amr M., Hegazy, Mohamed A. F., Okasha, Kamal, Eid, Mohammed A., Hanteera, Moahmed S., Medina-Gomez, Carolina, Ikram, M. Arfan, Uitterlinden, Andre G., Ripatti, Samuli, Jermy, Bradley, Ruotsalainen, Sanni, Kristiansson, Kati, Koskelainen, Sami, Perola, Markus, Donner, Kati, Kivinen, Katja, Palotie, Aarno, Kaunisto, Mari, Julienne, Hanna, Aschard, Hugues, Deleuze, Jean-Francois, Debette, Stephanie, Tregouet, David-Alexandre, Abel, Laurent, Henches, Léo, Lefloch, Edith, Claire, Dandine-Roulland, Sakuntabhai, Anavaj, Bourgeron, Thomas, Olaso, Robert, Daian, Delphine Bacq, Pellegrin, Isabelle, Casanova, Jean-Laurent, Cobat, Aurélie, Jouanguy, Emmanuelle, Zhang, Qian, Ghosn, Jade, Mentré, France, Laouénan, Cédric, Tubiana, Sarah, Chirouze, Catherine, Quintana-Murci, Luis, Patin, Etienne, Duffy, Darragh, Boland, Anne, Carreras, Anna, Galván-Femenía, Iván, Farré, Xavier, Cortés, Beatriz, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Garcia-Aymerich, Judith, Castaño-Vinyals, Gemma, Dobaño, Carlota, van Heel, David A., Hunt, Karen A., Trembath, Richard C., Jacobs, Benjamin Meir, Huang, Qin Qin, Martin, Hilary C., Mason, Dan, Trivedi, Bhavi, Wright, John, Munisamy, Malathy, Finer, Sarah, Griffiths, Christopher J., McCarthy, Mark I., Rosenberger, Carrie, Lee, Jong Eun, Chang, Diana, Hammer, Christian, Hunkapiller, Julie, Mahajan, Anubha, Pendergrass, Rion, Sucheston-Campbell, Lara, Yaspan, Brian, Lee, Hyun Soo, Shin, Eunsoon, Jang, Hye Yoon, Kim, Sunmie, Kym, Sungmin, Kim, Yeon-Sook, Jeong, Hyeongseok, Kwon, Ki Tae, Kim, Shin-Woo, Kim, Jin Yong, Jang, Young Rock, Kim, Hyun ah, Lee, Ji yeon, Lee, Jeong Eun, Lee, Shinwon, Choe, Kang-Won, Kang, Yu Min, Jee, Sun Ha, Jung, Keum Ji, Park, Hyun-Young, Kim, Bong-Jo, Kim, Young Jin, Hwang, Mi Yeong, Yoon, Kyungheon, Pairo-Castineira, Erola, Rawlik, Konrad, Caulfield, Mark J., Baillie, J. Kenneth, Griffiths, Fiona, Bretherick, Andrew D., Stuckey, Alex, Odhams, Christopher A., Walker, Susan, Russell, Clark D., Malinauskas, Tomas, Wu, Yang, Shen, Xia, Elliott, Katherine S., Morrice, Kirstie, Keating, Sean, Wang, Bo, Rhodes, Daniel, Klaric, Lucija, Zechner, Marie, Parkinson, Nick, Fawkes, Angie, Murphy, Lee, Vitart, Veronique, Wilson, James F., Yang, Jian, Scott, Richard H., Moutsianas, Loukas, Law, Andy, Begg, Colin, Hendry, Sara Clohisey, Hinds, Charles, Horby, Peter, Knight, Julian, Ling, Lowell, Maslove, David, McAuley, Danny, Millar, Johnny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Ponting, Chris P., Rowan, Kathy, Semple, Malcolm G., Shankar-Hari, Manu, Summers, Charlotte, Walsh, Timothy, Pan, Jacqueline, Grau, Neus, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Bociek, Aneta, Campos, Sara, Arbane, Gill, Ostermann, Marlies, Cha, Mina, DAmato, Fabiola, Kosifidou, Eirini, Lorah, Shelley, Morera, Kyma, Brady, Laura, Hugill, Keith, Henning, Jeremy, Bonner, Stephen, Headlam, Evie, Jones, Jessica, List, Abigail, Morley, Joanne, Welford, Amy, Kamangu, Bobette, Ratnakumar, Anitha, Shoremekun, Abiola, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavros, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Zongo, Olivier, Wood, Suzanne, Zak, Anne, Collier, David, Mundy, Manuela, Thompson, Christopher, Pritchard, Lisa, Gellamucho, Minnie, Cartlidge, David, Bandla, Nageswar, Bailey, Lucy, Davies, Michelle, Delaney, Jane, Scott, Leanne, Abdelrazik, Marwa, Alasdair, Frater, Carter, David, Elhassan, Munzir, Ganesan, Arunkumar, Jenkins, Samuel, Lamond, Zoe, Purohit, Dharam, Rohit, Kumar, Saleem, Malik, Wall, Alanna, Xavier, Kugan, Bakthavatsalam, Dhanalaksmi, Gehad, Kirolos, Gnanapragasam, Pakeerathan, Jain, Kapil, Jain, Swati, Malik, Abdul, Pappachan, Naveen, Moreno-Cuesta, Jeronimo, Haldeos, Anne, Vincent, Rachel, Oziegb, Maryjane, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, Knighton, Abigail, Nayak, Monalisa, Pappa, Evita, Saha, Rohit, Saha, Sian, Dodd, Andrew, O’Reilly, Kevin, McPhail, Mark, Clarey, Emma, Noble, Harriet, Smith, John, Coghlan, Phoebe, Brett, Stephen, Gordon, Anthony, Templeton, Maie, Antcliffe, David, Banach, Dorota, Darnell, Sarah, Fernandez, Ziortza, Jepson, Eleanor, Mohammed, Amal, Rojo, Roceld, Arias, Sonia Sousa, Gurung, Anita Tamang, Wong, Jenny, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Waite, Alicia A. C., Williams, Karen, Waugh, Victoria, Welters, Ingeborg, Emblem, Jessica, Norris, Maria, Shaw, David, Bashyal, Archana, Beer, Sally, Hutton, Paula, McKechnie, Stuart, Davidson, Neil, Mathew, Soya, Readion, Grace, Ryu, Jung, Wilson, Jean, Agrawal, Shruti, Elston, Kay, Jones, Megan, Meaney, Eoghan, Polgarova, Petra, Elbehery, Muhammad, Daubney, Esther, Ng, Anthony, Marshall, Jocelyn, Pathan, Nazima, Stroud, Katerina, White, Deborah, Andrew, Angela, Ashraf, Saima, Clark, Amy, Dent, Martin, Langley, Margaret, Peters, Cecilia, Ryan, Lucy, Sampson, Julia, Wei, Shuying, Baddeley, Alice, Meredith, Megan, Morris, Lucy, Gibbons, Alexandra, McLoughlin, Lisa, Delgado, Carlos Castro, Clark, Victoria, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Harrison, Abiola, Hurt, William James, Kanu, Rebecca, Kinch, Ashley, Leaver, Susannah, Lisboa, Ana, Mathew, Jisha, Patel, Kamal, Saluzzio, Romina Pepermans, Rawlins, John, Samakomva, Tinashe, Shah, Nirav, Sicat, Christine, Texeira, Joana, Queiroz, Joana Gomes De, Gloria, Edna Fernandes Da, Maccacari, Elena, Yun, Nikki, Manna, Soumendu, Farnell-Ward, Sarah, Maizcordoba, Maria, Thanasi, Maria, Ali, Hawakin Haji, Hastings, Janice, Grauslyte, Lina, Hussain, Musarat, Ruge, Bobby, King, Sam, Pogreban, Tatiana, Rosaroso, Lace, Smith, Helen, Phull, Mandeep-Kaur, Adams, Nikkita, Franke, George, George, Aparna, Salciute, Erika, Wong, Joanna, Dunne, Karen, Flower, Luke, Sharland, Emma, Sra, Sukhmani, Andrew, Gillian, Callaghan, Marie, Barclay, Lucy, Marshall, Lucy, Amamio, Maria, Birch, Sophie, Briton, Kate, Clark, Sarah, Doverman, Katerine, Hope, Dave, Mcculloch, Corrienne, Simpson, Scott, Singleton, Jo, Fernandez, Rita, Allen, Meryem, Baptista, David, Crowe, Rebecca, Fox, Jonathan, Khera, Jacyntha, Loveridge, Adam, McKenley, India, Morino, Eriko, Naranjo, Andres, O’Connor, Denise, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Herdman-Grant, Rosie, Joseph, Anna, Nown, Angela, Rose, Steve, Pogson, David, Boxall, Helen, Brimfield, Lutece, Claridge, Helen, Daly, Zoe, George, Shenu, Gribbin, Andrew, Cheema, Yusuf, Cutler, Sean, Richards, Owen, Roynon-Reed, Anna, Cherian, Shiney, Heron, Anne Emma, Williams, Gemma, Szakmany, Tamas, Waters, Abby, Collins, Kim, Dunhill, Jill, Jones, Ffion, Morris, Rebecca, Ship, Lucy, Cardwell, Amy, Ali, Syamlan, Bhatterjee, Ravi, Bolton, Rachel, Chukkambotla, Srikanth, Coleman, Dabheoc, Dalziel, Jack, Dykes, Joseph, Fine, Christopher, Gay, Bethan, Goddard, Wendy, Goodchild, Drew, Harling, Rhiannan, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Matt, Roseanna, Ryan-Smith, Janet, Saad, Samuel, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Kazi, Aayesha, Smith, Matthew, Collier, Heather, Davison, Chloe, Duberley, Stephen, Hargreaves, Jeanette, Hartley, Janice, Patel, Tahera, Smith, Ellen, Kent, Alissa, Goodwin, Emma, Zaki, Ahmed, Tibke, Clare, Hopkins, Susan, Gerrard, Hywel, Jackson, Matthew, Bennett, Sara, Marsh, Liane, Mills, Rebecca, Bell, Jessica, Campbell, Helen, Dawson, Angela, Dodds, Steve, Duffy, Stacey, Gallagher, Lisa, McCafferty, Gemma, Short, Stacey, Smith, Tracy, Thomas, Kirsty, Walker, Claire, Reynolds, Jessica, Yates, Bryan, McKie, Hayley, Panteli, Maria, Thompson, Maria, Waddell, Gail, Beger, Sarah De, Abraheem, Azmerelda, Dunmore, Charlie, Girach, Rumanah, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Brearey, Stephen, Burchett, Caroline, Cawley, Kathryn, Faulkner, Maria, Jeffrey, Helen, Bamford, Peter, Shaikh, Firdaus, Slack, Lauren, Davies, Angela, Brooke, Hollie, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Sandhu, Rajdeep, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Buckley, Sarah, Sloan, Brendan, Rose, Alastair, Major, Amy, Metcalfe, Alexandra, Almaden-Boyle, Christine, Austin, Pauline, Chapman, Susan, Eros, Alexandre, Cabrelli, Louise, Cole, Stephen, Whyte, Clare, Casey, Matt, Bafitis, Vasileios, Tsinaslanidis, George, George, Cassandra, Khade, Reena, Black, Christopher, Ashok, Sundar Raj, Farley, Sean, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Williams, Marie, Newey, Luke, Toghill, Hannah, Lewis, Sophie, Rees, Tabitha, Battle, Ceri, Baker, Mark, Travers, Jenny, Chesters, Karen, Baxter, Nicola, Arnott, Andrew, McCreath, Gordan, McParland, Christopher, Rooney, Laura, Sim, Malcolm, Henderson, Steven, Abel, Lynn, Dalton, Carol, Kennedy-Hay, Sophie, O’Donohoe, Lynn, O’Hare, Megan, Orlikowska, Izabela, Parker, Natasha, McNeela, Fiona, Lyle, Amanda, Hughes, Alistair, Radhakrishnan, Jayachandran, Gibson, Sian, Bancroft, Hollie, Bellamy, Mary, Daglish, Jacqueline, Kadiri, Salma, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Peterkin, Zhane, Scriven, James, Carmody, Margaret, Cottle, Juliet, Peasgood, Emily, de Gordoa, Laura Ortiz-Ruiz, Phillips, Claire, Skinner, Denise, Cinquina, Zoe, Howard, Kate, Joy, Rosie, Roche, Samantha, Birkinshaw, Isobel, Carter, Joseph, Ingham, Jo, Marshall, Nicola, Pearson, Harriet, Scott, Zoe, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Bamford, Amy, Hull, Diana, Ahmadhaider, Nafeesah, Bates, Michelle, McGhee, Christopher, Ellis, Hannah, Howe, Gwenllian Sera, Singh, Jayaprakash, Stroud, Natalie, Roche, Lisa, Lynch, Ceri, Deacon, Bethan, Pothecary, Carla, Smeaton, Justyna, Agravante, Kevin, Krishnamurthy, Vinodh, Diaba, Cynthia, John, Lincy, Lim, Lai, Jha, Rajeev, Egan, Jasmine, Felton, Timothy, Glasgow, Susannah, Padden, Grace, Choudhr, Ozerah, Bradley-Potts, Joanne, Moss, Stuart, Lingeswaran, Saejohn, Alexander, Peter, Brandwood, Craig, Fiouni, Sofia, Ward, Luke, Allen, Schvearn, Shaw, Jane, Smith, Christopher, Adanini, Oluronke, Collins, Rebecca, Msiska, Maines, Ofori, Linda, Bhatia, Nikhil, Dolan, Hayley, Brunton, Mark, Caterson, Jess, Coles, Holly, Keating, Liza, Tilney, Emma, Jacques, Nicola, Frise, Matthew, Armistead, Jennifer, Bartley, Shauna, Bhuie, Parminder, Rai, Sabi, Tomkova, Gabriela, Greer, Sandra, Shuker, Karen, Tridente, Ascanio, Dobson, Emma, Hunt, Jodie, Tully, Redmond, Dearden, Joy, Drummond, Andrew, Kamath, Prakash, Bullock, Emily, Mulcahy, Michelle, Munt, Shelia, O’Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Scott, Chloe, Winnard, Sarah, Hasni, Nurkamalia, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Beavis, Sarah, Bishop, Lauren, Cart, Cindy, Dale, Katie, Kelly-Baxter, Mary, Mendelski, Adam, Moakes, Emma, Smith, Rheanna, Woodward, Jan, Wright, Stephanie, Allan, Angela, Botello, Adriana, Liew, Jade, Medhora, Jasmine, Trumper, Erin, Savage, Felicity, Scott, Teresa, Place, Marc, Kaye, Callum, Benyon, Sarah, Marriott, Suzie, Park, Linda, Quinn, Helen, Skyes, Daisy, Zitter, Lily, Baines, Kizzy, Gordon, Elizabeth, Keenan, Samantha, Pitt, Andrew, Duffy, Katharine, Ireland, Jane, Semple, Gary, Turner, Lynne, Cathcart, Susanne, Rimmer, Dominic, Puxty, Alex, Puxty, Kathryn, Hurst, Andrew, Miller, Jennifer, Speirs, Susan, Walker, Lauren, Bradshaw, Zena, Brown, Joanna, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Warden, Scott, Beasley, Alanna, Stoddard, Emma, Benham, Leonie, Cupitt, Jason, Caswell, Melanie, Elawamy, Lisa, Wignall, Ashleigh, Roberts, Belinda, Golding, Hannah, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Golder, Kim, Jones, Oliver, Cusack, Rebecca, Bolger, Clare, Burnish, Rachel, Carter, Michael, Jackson, Susan, Salmon, Karen, Biss, Jonathan, Aquino, Maia, Croft, Maria, Frost, Victoria, White, Ian, Govender, Keshnie, Webb, Natasha, Stapleton, Liana, Wells, Colin, Nikitas, Nikitas, Sanchez - Rodriguez, Ana, Spencer, Kayleigh, Stowe, Bethan, Izzard, Yvonne, Poole, Michelle, Monnery, Sonja, Trotman, Sallyanne, Beech, Valerie, Combes, Edward, Joefield, Teishel, Covernton, Patrick, Savage, Sarah, Woodward, Elizabeth, Camsooksai, Julie, Reschreiter, Henrik, Barclay, Charlotte, DeAth, Yasmin, Dube, Judith, Humphrey, Charlotte, Jenkins, Sarah, Langridge, Emma, Milne, Rebecca, Wadams, Beverley, Woolcock, Megan, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, James, MacGoey, Patrick, O’Neil, Pauline, Price, Richard, Sundaram, Radha, Rodden, Natalie, Thomson, Nicola, Rooney, Kevin, Currie, Susan, Henderson, Philip, Ogg, Bethan, Whiteley, Simon, Wilby, Liz, Long, Kate, Matthew, Shailamma, Salada, Sheila, Trott, Susan, Watts, Sarah, Friar, Zoe, Speight, Abigail, Bastion, Victoria, Chandna, Humza, Djeugam, Brice, Haseeb, Muhammad, Kent, Harriet, Lubimbi, Gamu, Murdoch, Sophie, Thomas, Alastair, David, Beena, Lorusso, Rachel, Vochin, Ana, Penacerrada, Melchizedek, Wulandari, Retno, Heath, Charlotte, Jakkula, Srinivas, Morris, Anna, Ahmed, Ashar, Nune, Arvind, Buttriss, Claire, Whitaker, Emma, Davey, Miriam, Golden, David, Acklery, Amy, Fernandes, Fabio, Seaman, Bec, Earl, Victoria, Collins, Amy, Khaliq, Waqas, Adam, Rachel, Treus, Estefania, Holland, Sarah, Alfonso, Jordan, Blackledge, Bethan, Bruce, Michelle, Durrans, Laura Jayne, Eltayeb, Ayaa, Harris, Jade, Hey, Samuel, Hruska, Martin, Lamb, Thomas, Rothwell, Joanne, Fitzgerald, Adele, Lindergard, Gabriella, T-Michael, Helen, Duncan, Tracey, Baxter-Dore, Sharon, Cooper, Lisa, Fox, Claire, Guerin, Jacinta, Hodgkiss, Tracey, Connolly, Karen, McAlinden, Paul, Bridgett, Victoria, Fearby, Maggie, Gulati, A., Hanson, Helen, Kelly, Sinead, McCormack, Louise, Nixon, Rachel, Robinson, Philip, Slater, Victoria, Stephenson, Elaine, Webster, Andrea, Webster, K., Hays, Carole, Hudson, Anne, Patel, Bijal, Clement, Ian, Davis, John, Francis, Sarah, Jerry, Douglas, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Cabral-Ortega, Llucia, Hines, Matthew, Martinson, Victoria, Stones, Elizabeth, Winter, Karen, Barrow, Esther, Wylie, Katharine, Baines, Deborah, Birchall, Katie, Kolakaluri, Laurel, Clark, Richard, Sukumaran, Anila, Barker, Melanie, Paripoorani, Deborah, Smith, Lara, Taylor, Charlotte, Downes, Charlotte, Hayman, Melanie, Riches, Katie, Daniel, Priya, Subramanian, Deepak, Holding, Kathleen, Hilton, Mary, Mcdonald, Carly, Richardson, Georgina, Halladay, Georgia, Harding, Peter, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Parker, Robert, Lloyd, Michaela, Smith, Leanne, Kelly, Charlie, Lazo, Maria, Neal, Alan, Walton, Olivia, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Callam, Sara, Hudig, Lisa, Keshet-Price, Jocelyn, Stammers, Katie, Convery, Karen, Randell, Georgina, Fottrell-gould, Deirdre, Mwaura, Esther, Sutherland, Sara-Beth, Stewart, Richard, Mew, Louise, Wren, Lynn, Thrasyvoulou, Laura, Willis, Heather, Hopkins, Bridget, Lenton, Daniel, Roberts, Abigail, Bokhari, Maria, Lucas, Rachael, McCormick, Wendy, Ritzema, Jenny, Linnett, Vanessa, Sanderson, Amanda, Wild, Helen, Flanagan, Rebecca, Hull, Robert, Rhead, Kat, McKenna, Emma, Hughes, Gareth, Anderson, Jennifer, Jones, Kelly, Latham, Scott, Riley, Heather, Coulding, Martina, Clark, Martyn, McCormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Jude, Edward, Kilroy, Susan, Apetri, Elena, Basikolo, Cathrine, Catlow, Laura, Collis, Matthew, Doonan, Reece, Harvey, Alice, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, McMorrow, Liam, Michael, Angiy, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Dark, Paul, Charles, Bethan, McLaughlan, Danielle, Slaughter, Melanie, Horner, Dan, Marsden, Tracy, Andrews, Joyann, Beech, Emily, Akinkugbe, Olugbenga, Bamford, Alasdair, Belfield, Holly, Jones, Gareth A. L., McHugh, Tara, Meghari, Hamza, Ray, Samiran, Tomas, Ana Luisa, O’Neill, Lauran, Peters, Mark, Bell, Michael, Benkenstein, Sarah, Chisholm, Catherine, Davies, Charlene, Kupiec, Klaudia, Payne, Caroline, Halls, Joanna, Blakemore, Hayley, Goff, Elizabeth, Hayes, Kati, Smith, Kerry, Stephens, Deanna, Worner, Ruth, Borislavova, Borislava, Faulkner, Beverley, Thomas, Matt, Cookson, Ruth, Gendall, Emma, Larman, Georgina, Pope, Rebecca, Smalira, Artur, Priestley, Victoria, Cosier, Tracey, Millen, Gemma, Rand, James, Schumacher, Natasha, Sandhar, Roxana, Weston, Heather, Richardson, Neil, Cooper, Lucy, Jones, Cathy, Huang, Ya-Wen Jessica, Jacob, Reni, Denmade, Craig, Mcintyre, Lewis, Trodd, Dawn, Martin, Jane, Watson, Geoff, Bevan, Emily, Wreybrown, Caroline, Bano, Shereen, Bellwood, Ruth, Bentley, Michael, Bromley, Matt, Gurr, Lucy, Ledgard, Camilla, McGowan, Janet, Pye, Kate, Sellick, Kirsten, Stacey, Amelia, Warren, Deborah, Wilkinson, Brian, Akeroyd, Louise, Shafique, Huma, Morgan, James, Shorter, Susan, Swinger, Rachel, Waters, Emily, Lawton, Tom, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Davies, Llinos, Easton, Jack, Kumar, Sumit, Lean, Richard, Mackay, Callum, Pugh, Richard, Qiu, Xinyi, Rees, Stephanie, Scanlon, Jeremy, Lewis, Joanne, Menzies, Daniel, Bolger, Annette, Davies, Gwyneth, Davies, Jennifer, Garrod, Esther, Jones, Helen, Manley, Rachel, Williams, Hannah, Frankham, Jordan, Pitts, Sally, White, Nigel, Branney, Debbie, Tiller, Heather, Efford, Georgia, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Bewley, Jeremy, Coleman, Christina, Corcoran, Katie, Morano, Eva Maria Hernandez, Shiel, Rachel, Webster, Denise, Bonnici, Josephine, Daniel, Eleanor, Dell, Abbie, Kent, Melanie, Wilkinson, Ami, Brown, Ellen, Kay, Andrea, Campbell, Suzanne, Cowton, Amanda, Birt, Mark, Greenaway, Vicki, Potts, Kathryn, Hutton, Clare, Shepperson, Andrew, Forsey, Miranda, Nicholson, Alice, Vertue, Mark, Riches, Joanne, Kaliappan, Agilan, Nicholson, Anne, MacCallum, Niall, Raith, Eamon, Bercades, Georgia, Hass, Ingrid, Brealey, David, Martir, Gladys, Reyes, Anna, Smyth, Deborah, Zapatamartinez, Maria, Alvaro, Ana, Jetha, Champa, Ma, Louise, Booker, Lauren, Mostoles, Loreta, Pratley, Anezka, Altabaibeh, Abdelhakim, Parmar, Chetan, Gilbert, Kayleigh, Ferguson, Susie, Shepherd, Amy, Morris, Sheila, Baruah, Rosie, Lloyd, Georgina, Bell, Stephanie, Rivers, Vanessa, Purewal, Bally, Hammerton, Kate, Anderson, Susan, Birch, Janine, Collins, Emma, Oleary, Ryan, Cornell, Sarah, Jarmain, Jordan, Rogerson, Kimberley, Wakinshaw, Fiona, Woods, Lindsey, Rostron, Anthony, Elcioglu, Zeynep, Roy, Alistair, Bell, Gillian, Dickson, Holly, Wilcox, Louise, Katary, Amro, English, Katy, Hutter, Joanne, Pawley, Corinne, Doble, Patricia, Shovelton, Charmaine, Vaida, Marius, Purnell, Rebecca, Thomas, Ashly, Cagova, Lenka, Fofano, Adama, Holcombe, Helen, Mitchell, Alice Michael, Mwaura, Lucy, Praman, KrithivasanÂ, Garnr, Lucie, Mepham, Sue, Paques, Kitty, Vuylsteke, Alain, Mackie, Jennifer, Pearn, Carmen, Zamikula, Julie, Nyirenda, Maggie, Capozzi, Lisa, Reece-Anthony, Rosie, Noor, Hazma, Nilo, Alfa Cresia, Grove, Michelle, Daniel, Amelia, Finn, Joanne, White, Nikki, Saha, Rajnish, Badal, Bibi, Ixer, Karen, Duffin, Donna, Player, Ben, Hill, Helen, Cole, Jade, Brooks, Jenny, Davies, Rhys, Hunt, Lauren, Thomas, Emma, Williams, Angharad, Oblak, Metod, Thankachen, Mini, Irisari, Jamie, Sayan, Amrinder, Popescu, Monica, Finch, Cheryl, Jamieson, Andrew, Quinn, Alison, Cooper, Joshua, Liderth, Sarah, Waddington, Natalia, Burn, Iona, Manso, Katarina, Penn, Ruth, Tebbutt, Julie, Thornton, Danielle, Winchester, James, Hambrook, Geraldine, Shanmugasundaram, Pradeep, Craig, Jayne, Simpson, Kerry, Higham, Andrew, Sibbett, Louise, Paine, Sheila, Reed, Annabel, Conyngham, Jo-Anna, Mupudzi, Mcdonald, Thomas, Rachel, Wright, Mary, Griffin, Denise, Partridge, Richard, Corral, Maria Alvarez, Muchenje, Nycola, Sitonik, Mildred, Butler, Aaron, Folkes, Linda, Fox, Heather, Gardner, Amy, Helm, David, Hobden, Gillian, King, Kirsten, Margalef, Jordi, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Baird, Yolanda, Gomez, Raquel, Martin, Darren, Hodgson, Luke, Corin, Clinton, Sidall, Erikka, Szabo, Densie, Floyd, Sharon, Davies, Hannah, Austin, Karen, Kelsall, Olivia, Wood, Hannah, Cornell, Thomas, Ralph, Kate, Bean, Sarah, Burt, Karen, Spivey, Michael, Richards, Carol, Tedstone, Rachel, Carmody, Siobhain, Zhao, Xiaobei, Page, Valerie, Guanco, Mark Louie, Hoxha, Elvira, Zorloni, Camilla, Dean, Charlotte, Jones, Emma, Carter, Emma, Dunn, Joshua, Kong, Thomas, Mahenthran, Mervin, Marsh, Chris, Holland, Maureen, Keenan, Natalie, Mahmoud, Mohamed, Lyons, Marc, Wassall, Helen, Young, Meghan, Bradley, Paul, Burda, Dorota, Donlon, Sinead, Harden, Lesley, Harris, Celia, Mayangao, Irving, Montaser, Rugia, Mtuwa, Sheila, Piercy, Charles, Smith, Eleanor, Stone, Sarah, Verula, Jerik, Blackman, Helen, Marriott, Cheryl, Michalak, Natalia, Creagh-Brown, Ben, Salberg, Armorel, Boyer, Naomi, Pristopan, Veronika, Maynard, Victoria, Walker, Rachel, Hormis, Anil, Collier, Dawn, Graham, Cheryl, McCormick, Jake, Warrington, Jake, Cosgrove, Denise, McFarland, Denise, Ratcliffe, Judith, Charnock, Rob, Wynter, Inez, Gill, Mandy, Kirk, Jill, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Jardine, Catherine, Hay, Alasdair, Williams, Dewi, Durga, Latha, Hibbert, Meg, Kennard-Holden, Gareth, Woodford, Chrsitopher, Tetla, Dariusz, Price, Alicia, Thomas, Alice, Thorpe, Chris, Knights, Ellen, Ward, Donna, Laha, Shondipon, Verlander, Mark, Williams, Alexandra, Prout, Rachel, Langton, Helen, Watters, Malcolm, Hunt, Charlotte, Novis, Catherine, Arif, Sarwat, Cunningham, Amy, Hewitt, Claire, Hindale, Julia, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susie, Tavares, Silivia, Barber, Russell, Hilldrith, Annette, Hubbard, Kelly, Egginton, Dawn, Clark, Michele, Purvis, Sarah, Sinclair, Simon, Collins, Vicky, Landeg, Bethan, Sell, Craig, Coetzee, Samantha, Gales, Alistair, Otahal, Igor, Icke, Becky, Raj, Meena, Williams, Caroline, Williams, Jill, Hill, Lucy, Kayani, Abdul, Masunda, Bridgett, Gondo, Prisca, Atayeva, Nigara, Cruz, Carina, Pattison, Natalie, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Newton, Maria, Al-Moasseb, Hassan, Behan, Teresa, Player, Jasmine, Stead, Rachael, Mitra, Atideb, Nauyokas, Kirsty, Humphreys, Sally, Cockerill, Helen, Tampsett, Ruth, Postovalova, Evgeniya, Coventry, Tina, McGregor, Amanda, Fowler, Susan, Macmahon, Mike, Cochrane, Patricia, Pirie, Sandra, Hanley, Sarah, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Ishaq, Tahira, Kelly, Diane, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Merwaha, Ekta, Nortcliffe, Tonicha, Shaw, Lisa, Shaw, Ryan, Wood, Tracy, Bayo, Lee-Ann, Usher, Miranda, Wilson, Alison, Kitson, Ross, Pinnell, Jez, Robinson, Matthew, Boltwood, Kaitlin, Birch, Jenny, Bough, Laura, Tutton, Rebecca, Winter-Goodwin, Barbara, Goodsell, Josie, Taylor, Kate, Williams, Patricia, Williams, Sarah, Cave, Ashleigh, Rees, James, Imeson-Wood, Janet, Smith, Jacqueline, Amin, Vishal, Karthik, Komala, Kausar, Rizwana, Anastasescu, Elena, Reid, Karen, Anumakonda, Vikram, Stoddart, Ella, Demetriou, Carrie, Eckbad, Charlotte, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, White, Katie, Hierons, Sarah, Kelly, Fiona, Serrano-Ruiz, Alfredo, Evans, Gabrielle, Nicol, Liz, Wilkins, Joy, Hulacka, Kim, Debreceni, Gabor, Brown, Alison, Crickmore, Vikki, Hill, Kay, Kannan, Thogulava, Dagutao, Zenaida, Beesley, Kate, Lewis, Alison, Perry, Jess, Antony, Sherly, Board, Sarah, Buckley, Clare, Pippard, Lucy, Tanate, Alfonso, Wood, Diane, Kubisz-Pudelko, Agnieska, Gouda, Ayman, Auld, Fiona, Donnachie, Joanne, Murdoch, Euan, Prentice, Lynn, Runciman, Nikole, Senaratne, Dhaneesha, Short, Abigail, Sweeney, Laura, Symon, Lesley, Todd, Anne, Turner, Patricia, McCann, Erin, Salutous, Dario, Edmond, Ian, Whitelaw, Lesley, Bland, Yvonne, Kajtor, Istvan, Kavanagh, Lisa, Singler, Karen, Linfield-Brown, George, Moore, Luke Stephen Prockter, Vizcaychipi, Marcela, Martins, Laura, Moore, Luke, Bull, Rhian, Carungcong, Jaime, Allen, Louise, Beranova, Eva, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turney, Sharon, Hazelton, Tracy, Tutt, Gabriella, Arora, Mansi, Turki, Salah, Sinfield, Emily, Deery, Joanne, Ramos, Hazel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Thwaites, Vicky, Patel, Brijesh, Kamal, Liyanage, Zborowski, Anelise Catelan, Coe, Ryan, Anderson, Madeleine, Beadle, Jane, Coates, Charlotte, Collins, Katy, Crowley, Maria, Johnson, Laura, King, Laura, Paramsothy, Remi, Sargeant, Janet, Silva, Pedro, Stuart, Carmel, Taylor, June, Tyl, David, Wakefield, Phillipa, Kamundi, Charlotte, Olufuwa, Olumide, Belagodu, Zakaulla, Gherman, Anca, Oakley, Naomi, Allan, John, Geary, Tim, Meikle, Alistair, O’Brien, Peter, Wood, Stephen, Clark, Andrew, Houston, Gordon, Black, Karen, Clarkson, Michelle, D’Sylva, Stuart, Morrison, Alan, Norman, Kathryn, Taylor, Margaret, Clements, Suzanne, Cohrane, Catriona, Gonzalez, Nora, Strachan, Dominic, Beith, Claire, Moar, Kirsten, Anderson, Peter, Archer, Katie, Burtenshaw, Andrew, Clayton, Sarah, Cother, Naiara, Cowley, Nicholas, Davis, Caroline, Digby, Stephen, Durie, Alison, Harrison, Alison, Low, Emma, McAlindon, Michael, McCurdy, Alex, Morgan, Aled, Rankin, Tobias, Thrush, Jessica, Tranter, Helen, Vigurs, Charlie, Wild, Laura, Murphy, Lorna, Smythe, Michelle, Brickell, Kathy, Ali, Inthakab Ali Mohamed, Beaumont, Karen, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Coton, Zoe, Joshy, Aricsa, Blunt, Mark, Curgenven, Hollie, Botfield, Liam, Dexter, Catherine, Kuravi, Aditya, Butler, Joanne, Chadwick, Robert, Ranga, Poonam, Richardson, Lisa, Virgilio, Emma, Anwer, Maddiha, Garg, Atul, Botfield, Donna, Marriott, Xana, Stewart, Keely, Mullan, Dee, Gaylard, Jane, Nowak, Justyna, Jones, Sian, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Lancaster, Nicola, Matthews, Jamie, Wray, Gemma, Inweregbu, Ken, Cutts, Sarah, Miller, Katharine, Brady, Ailbhe, Chan, Rebekah, McIvor, Shane, Prady, Helena, Mathew, Bijoy, Little, Jeff, Furniss, Tim, Wright, Chris, King, Bernadette, Wasson, Christopher, O’Neill, Aisling, Turley, Christine, McGuigan, Peter, Collins, Erin, Finn, Stephanie, Green, Jackie, McAuley, Julie, Nair, Abitha, Quinn, Charlotte, Tauro, Suzanne, Ward, Kathryn, McGinlay, Michael, Reddy, Kiran, Ahmad, Norfaizan, Anderson, Samantha, Barker, Joann, Bauchmuller, Kris, Birchall, Kathryn, Bird, Sarah, Cawthron, Kay, Chetam, Luke, Cole, Joby, Donne, Ben, Foote, David, Ford, Amber, Hanratty, Helena, Harrington, Kate, Hesseldon, Lisa, Housley, Kay, Jackson, Yvonne, Jarman, Claire, Kibutu, Faith, Lenagh, Becky, Macharia, Irene, Masuko, Shamiso, Milner, Leanne, Newell, Helen, Nwafor, Lorenza, Oxspring, Simon, Phillips, Patrick, Raithatha, Ajay, Rowland-Jones, Sarah, Smith, Jacqui, Thompson, Roger, Trower, Helen, Walker, Sara, Watson, James, Wiles, Matthew, Lye, Alison, Willson, Jayne, Mills, Gary, Harris, Sansha, Hartill, Eleanor, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Nolan, Claire, Polgar, Oliver, Prendergast, Claire, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Mahay, Kanta, Reed, Anna, Meyrick, Hayley, Passmore, Heather, Farwell, James, O’Connell, Susan, Gregory, Jane, Barberis, Luigi, Harper, Rosemary, Smith, Tim, Armstrong, Diane, Bowey, Angie, Cowley, Anne, Corner, Andrew, Highgate, Judith, Rutherfurd, Claire, Taylor, Jo-Anne, Goodwin, Sarah, Eapen, Beena, Trim, Fiona, Donnison, Phil, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Kitching, Amy, McParland, Chantal, Packham, Sophie, Hairsine, Brigid, Andreou, Premetie, Hales, Dawn, Mathews, Megha, Patel, Rekha, Barry, Peter, Flint, Neil, Hailstone, Jessica, Ghuman, Navneet, Leonard, Bethany, Lees, Rachel, Butcher, Deborah, Leng, Katy, Butterworth-Cowin, Nicola, O’Sullivan, Susie, Ghosh, Alison, Williams, Emma, Adams, Colene, Agasou, Anita, Arden, Tracie, Beekes, Mandy, Bowes, Amy, Boyle, Pauline, Button, Heather, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, James, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Newman, Julie, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Donaldson, Denise, Capps, Nigel, Cale, Emily, Jose, Sanal, Osbourne, Wendy, Pajak, Susie, Rankin, Jayne, Tonks, Louise, Baird, Tracy, Harkins, Margaret, Ruddy, Jim, West, Joe, Duffield, Joseph, Mallon, Lewis, Smith, Oliver, Smuts, Sara, Campbell, Andy, Davies, Cate, Davies, Sarah, Hughes, Rachel, Jobes, Lisa, Whitehead, Victoria, Watkins, Clare, Bowman, Fiona, Milligan, Barry, McPherson, Liane, Metherell, Stella, Harris, Nichola, Lake, Victoria, Radford, Elizabeth, Smallwood, Andy, Gopal, Shameer, Vassell, Katherine, Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lennon, Liz, Rattray, Austin, Lee, Emma, Jones, Danielle, Parsons, Penny, Attwood, Ben, Jefferson, Paul, Ranganathan, Mohan, Atwal, Inderjit, Campbell, Bridget, Day, Angela, Stagg, Camilla, Haynes, Emma, Ahmed, Cecilia, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Joseph, Sibet, Maqsood, Zahira, Hussain, Samia, Hulme, Jonathan, Domingos, Patience, Kumar, Rita, Purewal, Manjit, Taylor, Becky, Bunni, Lara, Latif, Monica, Jennings, Claire, Jose, Shilu, Marshall, Rebecca, Metryka, Aleksandra, Subramanian, Gayathri, Burgoyne, Adam, Tyler, Amanda, Waldron, Joanne, Hilltout, Paula, Evitts, Jayne, Ward, Geraldine, Bremmer, Pamela, Hawkins, Carl, Jackman, Sophie, Ogorek, Michal, Ashby, Kylie, Thornton, Lorraine, Mercer, Pauline, Halkes, Matthew, Revill, Adam, Saint, Bryony, Fletcher, Jo, Netherton, Kimberley, Chablani, Manish, Kirkby, Amy, Roper, Amanda, Szymiczek, Kinga, Sutherland, Isobel, O’Brien, Linda, Connell, Joanne, Davies, Kim, Lewis, Tracy, Omar, Zohra, Perkins, Emma, Sathe, Sonia, Davies, Ellie, Lyon, Alex, Mapfunde, Isheunesu, Willis, Charlotte, Hitchcock, Rachael, Hall, Kathryn, King, Christopher, Fagan, Andrew, Nazari, Roonak, Worsley, Lucy, Allibone, Suzanne, Kasipandian, Vidya, Patel, Amit, Cutting, Parisa, Genetu, Roman, Mac, Ainhi, Murphy, Anthony, Ward, Sinead, Butt, Fatima, Ayers, Amanda, Harrison, Wendy, Mackintosh, Katherine, North, Julie, Ashton, Lydia, Bi, Rehana, Owen, Samantha, Winmill, Helen, Scholefield, Barney, Blowing, Hannah, Williams, Erin, Duskova, Michaela, Edwards, Michelle, Rees, Alun, Thomas, Helen, Brooks, Jolene, Phipps, Janet, Brooks, Suzanne, Dennis, Catherine, Parris, Vicki, Srikaran, Sinduya, Sukha, Anisha, McGregor, Alistair, Tiongson, Gerlynn, Adams, Katie, Andrew, Benedict, Brayne, Adam, Carter, Sasha, Findlay, Louise, Fisher, Emma, Jackson, Peter, Kaye, Duncan, Parkin, Juliet, Tuckey, Victoria, Hunt, Jane, Love, Nicholas, van Koutrick, Lynne, Hanson, Ashley, Dent, Kathy, Horsley, Elizabeth, Pearson, Sandra, Spencer, Sue, Hutchinson, Dorothy, Potoczna, Dorota, Akhtar, Muhammad Nauman, Cottam, Lisa-Jayne, Sanders, Jack, Garcia, Sara Mingo, pakou, Glykeria, Filipe, Helder, Maharajh, Amitaa, de Neef, Mark, Martin, Daniel, Eastgate, Christine, Teoh, Poh Choo, Barrett, Fiona, Bradley, Clare, Donaldson, Avril, Mascarenhas, Mairi, O’Hara, Marianne, Okeefe, Laura, Clarke, Noreen, Whiteside, Jonathan, Campbell, Rachael, Matheson, Joanna, McDonald, Deborah, Patience, Donna, Rice, Polly, Clapham, Melanie, Mutch, Rachel, Craig, Hannah, Poultney, Una, Burns, Karen, Twiss, Sophie, Barton, Janet, George, Linsha, Harrop, Clare, Mathew, Sherly, Wright, David Justin, Harrison, Rachel, Toohie, Jordan, Chandler, Ben, Turnbull, Alison, Mallinson, Janine, Elliott, Kerry, Wolf-Roberts, Rebecca, Tench, Helen, Hobrok, Maria, Loosley, Ronda, McGuinness, Heather, Sims, Tanya, Afolabi, Deborah, Allison, Kathryn Sian, Anderson, Taya, Dore, Rachael, Jones, Dawn, Rogers, Naomi, Saunderson, Paula, Whitbread, Jennifer, O’Malley, Laura, Rad, Laura, Hawcutt, Daniel, Aldridge, Jonathan, Tolson, Melanie, Garrioch, Sweyn, Tomlinson, Joanne, Grosdenier, Michael, Loader, David, Kapoor, Ritoo, Hector, Gemma, Scherewode, Joslan, Sri-Chandana, Chunda, Stephenson, Lorraine, Marsh, Sarah, Rosa, Arnold Dela, Jhanji, Shaman, Bemand, Thomas, Howle, Ryan, Baikady, Ravishankar Rao, Thomas, Benjamin, Black, Ethel, Tatham, Kate, Gurram, Sambasivarao, Watson, Ekaterina, Quaid, Sheena, Saunderson, Anne, O’Brien, Rachel, Moultrie, Sam, Service, Jen, Cheyne, Clare, Odam, Miranda, Wiliams, Alison, Barnes, Nicky, Csabi, Peter, Rocha, Joana Da, Glynou, Louika, Huffenberger, Amy, Bryant, Jade, Pickard, Amy, Roe, Nicholas, Bellini, Arianna, Mayer, Anton, Burrow, Amy, Colley, Natalie, Evans, Jayne, Howlett, Alex, Khalifeh, Zeinab, Pryce, Jerldine, Gorman, Claire, Brady, Rebecca, Timlick, Elizabeth, Antoine, Pierre, Gupta, Abhinhav, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tucci, Arianna, Tariq, Ambreen, Tagliavini, Emma, Ramsay, Becky, Fidler, Katy, Donnelly, Kevin, Hollis, Rebecca, Barr, Jocelyn, Boyd, Elizabeth, Irvine, Val, Shelley, Ben, Buckley, Julie, Hamilton, Charlene, Valdeavella, Kathryn, Bircham, Sarah, Liggett, Steven, Patil, Anand, Siddiq, Afshan, Goddard, Peter, Donovan, Sally, Zainy, Tala, Maleady-Crowe, Fiona, Todd, Linda, Salehi, Shahla, Elgar, Greg, Chan, Georgia, Arumugam, Prabhu, Patch, Christine, Rendon, Augusto, Bentley, David, Kingsley, Clare, Fowler, Tom A., Elliott, Paul, Tenesa, Albert, Aitkin, Emma, Aravindan, Latha, Armstrong, Ruth, Biggs, Heather, Boz, Ceilia, Brown, Adam, Chikowore, Primmy, Coutts, Audrey, Coyle, Judy, Cullum, Louise, Das, Sukamal, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Finernan, Paul, Fourman, Max Head, Furlong, Anita, Furniss, James, Gallagher, Bernadette, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Hamilton, Debbie, Hendry, Ross, Kearns, Naomi, Law, Dawn, Law, Rachel, Law, Sarah, Lidstone-Scott, Rebecca, Lauder, Christen, Macgillivray, Louise, Maclean, Alan, Mal, Hanning, McCafferty, Sarah, Mcmaster, Ellie, Meikle, Jen, Moore, Shona C., Murphy, Sheena, Mybaya, Hellen, Oosthuyzen, Wilna, Zheng, Chenqing, Chen, Jiantao, Paterson, Trevor, Tucker, Petra, Schon, Katherine, Stenhouse, Andrew, Das, Mihaela, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Turtle, Lance, Wackett, Tony, Ward, Mairi, Weaver, Jane, Wrobel, Nicola, Rakitko, Alexander, Ilinsky, Valery, Yermakovich, Danat, Popov, Iaroslav, Chernitsov, Alexander, Kovalenko, Elena, Vergasova, Ekaterina, Prokhorov, Alexandr, Krasnenko, Anna, Plotnikov, Nikolay, Stetsenko, Ivan, Kim, Anna, Cirulli, Elizabeth T., Schiabor Barrett, Kelly M., Bolze, Alexandre, White, Simon, Washington, Nicole L., Lu, James T., Riffle, Stephen, Tanudjaja, Francisco, Wang, Xueqing, Ramirez, Jimmy M., Leonetti, Nicole, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Grzymski, Joseph J., Joshi, Madhvi N., Dixit, Raghav D., Shah, Pranay K., Upadhyay, Kamlesh J., Chuhan, Naresh T., Desai, Kairavi J., Shah, Meenakshi R., Modi, Bhavesh, Joshi, Chaitanya G., Pandit, Ramesh J., Singh, Indra, Ansari, Afzal I., Raval, Janvi N., Patel, Zarna Z., Moreno-Estrada, Andres, Vázquez-Pérez, Joel Armando, Castillejos-López, Manuel, Aquino-Gálvez, Arnoldo, Shamah-Levy, Teresa, Ávila-Arcos, María C., Luna, María Teresa Tusié, Hidalgo-Miranda, Alfredo, Barberena-Jonas, Carmina, Quinto-Cortés, Consuelo D., Ávila-Arcos, Marco Antonio, Huerta-Chagoya, Alicia, García-García, Lourdes, Barnetche, Jesús Martinez, Alpuche-Aranda, Celia, Rivera, Juan A., Gutiérrez, Tonatiuh Barrientos, Ochoa-Guzmán, Ana, Ordoñez-Sánchez, Maria Luisa, Segura-Kato, Yayoi, Herrera-Montalvo, Luis Alonso, Mendoza-Vargas, Alfredo, Reyes-Grajeda, Juan Pablo, Cruz-Cruz, Alonso D., Velázquez-Cruz, Rafael, Torres-Espíndola, Luz María, Sierra-Vargas, Martha Patricia, Camarena, Angel, Ruiz, Víctor, Chávez-Alderete, Jaime, Jaime-Capetillo, María Esther, Guadarrama-Pérez, Cristóbal, Zúñiga-Ramos, Joaquin, Olivera-Ramírez, Alejandra, Martínez, Miguel Angel López, Serna-Muñoz, Ricardo, Garmendia, Adriana, Namkoong, Ho, Okada, Yukinori, Imoto, Seiya, Katayama, Kazuhiko, Fukunaga, Koichi, Kitagawa, Yuko, Sato, Toshiro, Hasegawa, Naoki, Kumanogoh, Atsushi, Kimura, Akinori, Ai, Masumi, Tokunaga, Katsushi, Kanai, Takanori, Miyano, Satoru, Ogawa, Seishi, Edahiro, Ryuya, Sonehara, Kyuto, Shirai, Yuya, Ishii, Makoto, Kabata, Hiroki, Masaki, Katsunori, Kamata, Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Tanaka, Hiromu, Morita, Atsuho, Lee, Ho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Mikami, Yohei, Tomono, Kazunori, Kato, Kazuto, Matsuda, Fumihiko, Takahashi, Meiko, Hizawa, Nobuyuki, Takeda, Yoshito, Hirata, Haruhiko, Shiroyama, Takayuki, Miyawaki, Satoru, Suzuki, Ken, Maeda, Yuichi, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Takahashi, Kunihiko, Anzai, Tatsuhiko, Hasegawa, Takanori, Ito, Satoshi, Koike, Ryuji, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro, Nakajima, Jun, Nannya, Yasuhito, Omae, Yosuke, Takahashi, Kazuhisa, Harada, Norihiro, Hiki, Makoto, Takagi, Haruhi, Nakamura, Ai, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Ishiguro, Takashi, Takayanagi, Noboru, Isono, Taisuke, Takaku, Yotaro, Takano, Kenji, Anan, Ryusuke, Nakajima, Yukiko, Nakano, Yasushi, Nishio, Kazumi, Ueda, Soichiro, Hayashi, Reina, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Mitamura, Keiko, Saito, Fumitake, Ueda, Tetsuya, Azuma, Masanori, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Yoshiyama, Takashi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Watanabe, Kazuyoshi, Manabe, Tadashi, Ito, Fumimaro, Fukui, Takahiro, Funatsu, Yohei, Koh, Hidefumi, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Saito, Fukuki, Yoshiya, Kazuhisa, Yoshihara, Tomoyuki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Nishi, Koichi, Nishitsuji, Masaru, Tani, Maiko, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Ogura, Takashi, Kitamura, Hideya, Murohashi, Kota, Nakachi, Ichiro, Baba, Rie, Arai, Daisuke, Fuke, Satoshi, Saito, Hiroshi, Kuwahara, Naota, Fujiwara, Akiko, Okada, Takenori, Baba, Tomoya, Noda, Junya, Mashimo, Shuko, Yagi, Kazuma, Shiomi, Tetsuya, Hashiguchi, Mizuha, Odani, Toshio, Mochimaru, Takao, Oyamada, Yoshitaka, Mori, Nobuaki, Izumi, Namiki, Nagata, Kaoru, Taki, Reiko, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Gon, Yasuhiro, Fujitani, Shigeki, Tsuchida, Tomoya, Yoshida, Toru, Kagaya, Takashi, Kita, Toshiyuki, Sakagami, Satoru, Kimizuka, Yoshifumi, Kawana, Akihiko, Nakamura, Yoshihiko, Ishikura, Hiroyasu, Takata, Tohru, Kikuchi, Takahide, Taniyama, Daisuke, Nakamura, Morio, Kodama, Nobuhiro, Kaneyama, Yasunari, Maeda, Shunsuke, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Ito, Akihiro, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Hashimoto, Naozumi, Wakahara, Keiko, Ando, Akira, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Sageshima, Hisako, Nakada, Taka-Aki, Abe, Ryuzo, Shimada, Tadanaga, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Yamasaki, Masaki, Hashimoto, Satoru, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Takada, Minoru, Kanda, Hidenori, Komase, Yuko, Sano, Fumiaki, Asano, Koichiro, Oguma, Tsuyoshi, Harada, Masahiro, Takahashi, Takeshi, Shibusawa, Takayuki, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Izumo, Takehiro, Inomata, Minoru, Awano, Nobuyasu, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Kitagawa, Yuichiro, Yoshida, Shozo, Ogura, Shinji, Nishiyama, Kei, Yoshida, Kousuke, Beppu, Satoru, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Inoue, Yoshiaki, Yamagata, Kunihiro, Chiba, Shigeru, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Shibata, Yoko, Tanino, Yoshinori, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Imamura, Tomonori, Umeda, Akira, Shimada, Hisato, Endo, Mayu, Hayashi, Shinichi, Takahashi, Mai, Nakano, Shigefumi, Yatomi, Masakiyo, Maeno, Toshitaka, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Nishida, Nao, Kawai, Yosuke, Sugiyama, Masaya, Alawneh, Laith M., Maswadeh, Kinda B., Alsoub, Fatima S., AlRawashdeh, Tala J., Esawi, Ezaldeen, Abu Alragheb, Bayan O., Maswadeh, Ahmad B., Al-Kadash, Abdulfattah, Al-Ani, Abdallah, Alsafadi, Dana B., Shahin, Mohammad A., Qtaish, Nuseibah Al, Alawneh, Fade M., Abulail, Joseph A., Zhlawi, Hadi J., Alhousani, Tasneem N., Alzuraiqi, Mohammad R., Al-Ja’afreh, Mohammad M., Allouzy, Sara K., ALjalamdeh, Mothafer, Mansour, Tareq M., Alamer, Lina M., Issa, Ali Banni, Bani younis, Fatima M., Hawari, Feras I., Hayajneh, Wail A., Obeidat, Nathir M., Ahram, Mamoun, Zhlawi, Moh’d Wahib J., Alshaer, Walhan, Al-Kasasbeh, Malak M., Naffa, Randa G., Ismail, Mohammad A., Abdullah, Mohammed S., Ismail, Said I., Obeidat, Ma’en, Hernández Cordero, Ana I., Sin, Don D., Bossé, Yohan, Joubert, Philippe, Hao, Ke, Nickle, David, Timens, Wim, van den Berge, Maarten, Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Mandla, Ravi, Schroeder, Philip, Perez, Emma F., Lee, Seung Hyuk T., Flores-Silva, Fernando Daniel, Chiquete, Erwin, Cantú-Brito, Carlos, Sifuentes-Osornio, José, de León-Garduño, Alfredo Ponce, Román-Montes, Carla Marina, Chávez-Manzanera, Emma, Velasco, Donaji Gómez, Martagón-Rosado, Alexandro, Cruz-Bautista, Ivette, Gómez-Pérez, Francisco Javier, Díaz-Olavarrieta, Claudia, Valdés, Paloma Almeda, Muñóz-Hernández, Linda Liliana, Mehta, Roopa Pravin, Elías-López, Daniel, Tusié-Luna, Teresa, Pajukanta, Päivi, Sukhatme, Mihir G., Moreno-Macías, Hortensia, Ruth, Johnson, González-Behn-Eschenburg, Sebastián, García-Grimshaw, Miguel, Guillen-Pineda, Luz Elizabeth, de los Ángeles Vargas-Martínez, María, Rodríguez, Maribel, Rodríguez-Guillén, Rosario, Ordoñez, María Luisa, Rajme-López, Sandra, González-Lara, María Fernanda, Luna-Moreno, Dalia, de Jesús Suárez López, Jannet, Guillén-Quintero, Daniela Mariel, Vega, Juan, Duran-Coyote, Salvador, Guerra-García, María Teresa, Durán-Gómez, Michelle, Vigueras-Hernández, Alma, Ramírez-Jiménez, Marco Eduardo, Grajeda-González, Samara Lissete, Ramos-Galicia, Enrique Manuel, Ramírez-Carrillo, Martha Fernanda, Fernandez-Ruiz, Juan, Chirino-Pérez, Amanda, Romero-Molina, Ángel Omar, Zavaleta, David Alejandro Fuentes, Jaramillo, María Andrea Mac Donald, López, Katia Jarely Prieto, Incontri-Abraham, Diego, Rosado, Wendy Natalia, Catalán, María Alonso, Aguilar, Sonia Evelyn Vital, Zamudio, Ileana Paola Montero, Ruíz-Ruíz, Eduardo, de Jesús Carrera García, Kevin, Guerrero, Cristina Villarreal, Martínez, Ana Isabel Rodríguez, Moscoso-Sánchez, Rogelio, del Consuelo Rodríguez Mancilla, María, Villa, Antonio, Luna-Ramírez, Samuel Alejandro, Hernández-Hernández, Sergio, Frias, Erika, Campos, Alejandro, Morales-Sosa, Paola Alessandra, Toxqui-Merchant, Luis Enrique, García, Karla, Pasaniuc, Bogdan, Butte, Manish J., Geschwind, Daniel H., Aguilar-Salinas, Carlos A., Heidecker, Bettina, Kurth, Florian, Sander, Leif E., Skurk, Carsten, Landmesser, Ulf, Karadeniz, Zehra, Wang, Xiaomin, Poller, Wolfgang, Suwalski, Phillip, Ripke, Stephan, Braun, Alice, Kraft, Julia, Mayer, Alena, Lippert, Lena J., Helbig, Elisa T., Thibeault, Charlotte, Awasthi, Swapnil, Mbarek, Hamdi, Saad, Chadi, Al-Sarraj, Yaser, Badji, Radja Messai, Al-Muftah, Wadha, Thani, Asma Al, Afifi, Nahla, Sadiq, Fouzia, Khan, Mohammad I., Bhutta, Muhammad J., Khan, Hania, Khan, Madeeha, Ain, Quratul, Junaid, Ayesha, Khan, Ejaz A., Sypniewski, Mateusz, Lejman, Adrian, Zawadzki, Paweł, Sztromwasser, Paweł, Król, Zbigniew, Dobosz, Paula, Stojak, Joanna, Flores, Carlos, Carracedo, Ángel, Aguilar, Carlos, Arranz, María J., Baptista-Rosas, Raúl C., Bezerra, Joao F., Bezerra, Marcos A. C., Brugada, Ramón, Bustos, Matilde, Castano, Luis, Conde-Vicente, Rosa, Cordero-Lorenzana, M. Lourdes, De Martino-Rodríguez, Alba, Domínguez-Garrido, Elena, Fariñas, María Carmen, Gil-Fournier, Belén, Herrero, María José, Lattig, María Claudia, Martín-López, Caridad, Martín, Vicente, Martinez-Nieto, Oscar, Martinez-Lopez, Iciar, Mazzeu, Juliana F., Macías, Eleuterio Merayo, Cuerda, Victor Moreno, Silbiger, Vivian N., Oliveira, Silviene F., Parellada, Mara, Santos, Ney P. C., Pérez-Matute, Patricia, Perez, Patricia, Perucho, Teresa, Porras-Hurtado, Gloria L., Pujol, Aurora, Fernández-Rodríguez, Amanda, Jimenez-Sousa, María A., Rodríguez-Ruiz, Emilio, Rodriguez-Artalejo, Fernando, Rodriguez-Garcia, José A., Ruiz-Cabello, Francisco, Soria, José Manuel, Tamayo, Eduardo, Teper, Alejandro, Torres-Tobar, Lilian, Urioste, Miguel, Yáñez, Zuleima, Zarate, Ruth, Guillen-Navarro, Encarna, Ayuso, Carmen, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Lapunzina, Pablo, Cruz, Raquel, Diz-de Almeida, Silvia, Ceballos, Francisco C., Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Quintela, Inés, Pita, Guillermo, Gago-Domínguez, Manuela, Porras, Marta Sevilla, Tenorio-Castaño, Jair Antonio, Nevado, Julian, Aguado, Jose María, Aguilera-Albesa, Sergio, Almadana, Virginia, Almoguera, Berta, Alvarez, Nuria, Andreu-Bernabeu, Álvaro, Arango, Celso, Artiga, Maria-Jesus, Barreda-Sánchez, María, Belhassen-Garcia, Moncef, Boix-Palop, Lucía, Brion, María, Carbonell, Cristina, Castelao, Jose E., Cortes-Sanchez, Jose L., Corton, Marta, Darnaude, M. Teresa, del Campo-Pérez, Victor, de Bustamante, Aranzazu Diaz, Luchessi, Andre D., Eiros, Rocío, Sanabria, Gladys Mercedes Estigarribia, Fernández-Robelo, Uxía, Fernández-Villa, Tania, Gómez-Arrue, Javier, Álvarez, Beatriz González, de Quirós, Fernan Gonzalez Bernaldo, González-Peñas, Javier, Gutiérrez-Bautista, Juan F., Herrero-Gonzalez, Antonio, Borja, Anabel Liger, Lopez-Rodriguez, Rosario, Mancebo, Esther, Martinez-Resendez, Michel F., Martinez-Perez, Angel, Minguez, Pablo, Ortega-Paino, Eva, Paz-Artal, Estela, Pérez-Tomás, M. Elena, Pinsach-Abuin, Mel·lina, Pompa-Mera, Ericka N., León, Soraya Ramiro, Resino, Salvador, Fernandes, Marianne R., Ruiz-Hornillos, Javier, Ryan, Pablo, Souto, Juan Carlos, Tamayo-Velasco, Alvaro, Taracido-Fernandez, Juan Carlos, Valencia-Ramos, Juan, de Heredia, Miguel López, Pedersen, Ole B., Erikstrup, Christian, Ostrowski, Sisse R., Stefansson, Kari, Mikkelsen, Susan, Sørensen, Erik, Burgos, Celia, Andersen, Steffen, Brugdorf, Kristoffer, Hansen, Thomas F., Hjalgrim, Henrik, Jemec, Gregor B., Nyegaard, Mette, Werge, Thomas, Johansson, Pär I., Didriksen, Maria, Schwinn, Michael, Jacobsen, Rikke L., Hindhede, Lotte, Rostgaard, Klaus, Gudbjartsson, Daniel, Stefánsson, Hreinn, Þorsteinsdóttir, Unnur, Nielsen, Kaspar R., Bruun, Mie Topholm, Dinh, Khoa M., Larsen, Margit A. H., Sækmose, Susanne G., Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Tardif, Nicolas, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Heid, Iris M., Wagner, Ralf, Überla, Klaus, Winkler, Thomas W., Wiegrebe, Simon, Gorski, Mathias, Stark, Klaus J., Peterhoff, David, Einhauser, Sebastian, Niller, Hans-Helmut, Beileke, Stephanie, Johnson, Ruth, Freimer, Nelson, Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikolas, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Solomonson, Matthew, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Zhou, Wei, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicolas, Koelling, Nils, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlos, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler-Palacin, Pere, Colobran, Roger, Martin-Nalda, Andrea, Parra-Martínez, Alba, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas-Rodriguez, Elisa, Cal-Sabater, Paloma, Segura, Tomás, González-Villar, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Kanai, M, Andrews, S, Cordioli, M, Stevens, C, Neale, B, Daly, M, Ganna, A, Pathak, G, Iwasaki, A, Karjalainen, J, Mehtonen, J, Pirinen, M, Chwialkowska, K, Trankiem, A, Balaconis, M, Veerapen, K, Wolford, B, Ahmad, H, von Hohenstaufen Puoti, K, Boer, C, Boua, P, Butler-Laporte, G, Cadilla, C, Chwiałkowska, K, Colombo, F, Douillard, V, Dueker, N, Dutta, A, El-Sherbiny, Y, Eltoukhy, M, Esmaeeli, S, Faucon, A, Fave, M, Cadenas, I, Francescatto, M, Francioli, L, Franke, L, Fuentes, M, Durán, R, Cabrero, D, Harry, E, Jansen, P, Szentpéteri, J, Kaja, E, Kirk, C, Kousathanas, A, Krieger, J, Patel, S, Lemaçon, A, Limou, S, Lió, P, Marouli, E, Marttila, M, Medina-Gómez, C, Michaeli, Y, Migeotte, I, Mondal, S, Moreno-Estrada, A, Moya, L, Nakanishi, T, Nasir, J, Pasko, D, Pearson, N, Pereira, A, Priest, J, Prijatelj, V, Prokić, I, Teumer, A, Várnai, R, Romero-Gómez, M, Roos, C, 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C., Thompson, Wesley K., Fan, Chun Chieh, Johnson, Emma C., Niazyan, Lyudmila, Davidyants, Mher, Arakelyan, Arsen, Avetyan, Diana, Bekbossynova, Makhabbat, Tauekelova, Ainur, Tuleutayev, Mukhtar, Sailybayeva, Aliya, Ramankulov, Yerlan, Zholdybayeva, Elena, Dzharmukhanov, Jarkyn, Kassymbek, Kuat, Tsechoeva, Tatyana, Turebayeva, Gulsimzhan, Smagulova, Zauresh, Muratov, Timur, Khamitov, Sadyk, Kwong, Alex S. F., Timpson, Nicholas J., Niemi, Mari E. K., Rahmouni, Souad, Guntz, Julien, Beguin, Yves, Pigazzini, Sara, Nkambule, Lindokuhle, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gilles, Gofflot, Stéphanie, Bouysran, Youssef, Busson, Adeline, Peyrassol, Xavier, Wilkin, Françoise, Pichon, Bruno, Smits, Guillaume, Vandernoot, Isabelle, Goffard, Jean-Christophe, Tiembe, Nicky, Morrison, David R., Afilalo, Jonathan, Mooser, Vincent, Richards, J. 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Tsourlos, Stavros, Athanasiou, Lazaros, Kolios, Nikolaos-Gavriil, Pappa, Christiana, Papathanasiou, Alexandros, Pargana, Eleni, Nasiou, Maria, Kosmidou, Maria, Rapti, Iro, Ntotsikas, Evangelos, Chaliasos, Konstantinos, Ntzani, Evangelia, Evangelou, Evangelos, Gartzonika, Konstantina, Georgiou, Ioannis, Tzoulaki, Ioanna, Ellinghaus, David, Degenhardt, Frauke, Cáceres, Mario, Juzenas, Simonas, Lenz, Tobias L., Albillos, Agustín, Julià, Antonio, Prati, Daniele, Solligård, Erik, Garcia, Federico, Tran, Florian, Hanses, Frank, Baselli, Guido, Zoller, Heinz, Holter, Jan Cato, Fernández, Javier, Barretina, Jordi, Valenti, Luca, Bujanda, Luis, Buti, Maria, D’Amato, Mauro, Banales, Jesus M., Rosenstiel, Philip, Koehler, Philipp, Invernizzi, Pietro, de Cid, Rafael, Asselta, Rosanna, Schreiber, Stefan, Duga, Stefano, Hehr, Ute, Franke, Andre, Maya-Miles, Douglas, Hov, Johannes R., Karlsen, Tom H., Folseraas, Trine, Teles, Ana, Tanck, Anja, Gassner, Christoph, Azuure, Clinton, Wacker, Eike 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Muscatello, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier, Aurora, Cortes, Beatriz, Mateos, Beatriz, Nafria-Jimenez, Beatriz, Schaefer, Benedikt, Bellinghausen, Carla, Ferrando, Carlos, de la Horra, Carmen, Quereda, Carmen, Scollo, Chiara, Lange, Christoph, Hu, Cinzia, Paccapelo, Cinzia, Angelini, Claudio, Cappadona, Claudio, Bianco, Cristiana, Cea, Cristina, Sancho, Cristina, Hoff, Dag Arne Lihaug, Galimberti, Daniela, Haschka, David, Jiménez, David, Pestaña, David, Toapanta, David, Muñiz-Diaz, Eduardo, Azzolini, Elena, Sandoval, Elena, Binatti, Eleonora, Scarpini, Elio, Casalone, Elisabetta, Urrechaga, Eloisa, Paraboschi, Elvezia Maria, Pontali, Emanuele, Reverter, Enric, Calderón, Enrique J., Navas, Enrique, Contro, Ernesto, Arana-Arri, Eunate, Aziz, Fátima, Sánchez, Félix García, Ceriotti, Ferruccio, Martinelli-Boneschi, Filippo, Peyvandi, Flora, Blasi, Francesco, Malvestiti, Francesco, Medrano, Francisco J., Mesonero, Francisco, Rodriguez-Frias, Francisco, Müller, 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S., Elnagdy, Marwa H., Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T., El-Lawaty, Walaa M., Torky, Mohamed S., El-Shanshory, Mohamed R., Elzeiny, Ahmed, Rashad, Amal, Mansour, Tamer A., Yassen, Amr M., Hegazy, Mohamed A. F., Okasha, Kamal, Eid, Mohammed A., Hanteera, Moahmed S., Medina-Gomez, Carolina, Ikram, M. Arfan, Uitterlinden, Andre G., Ripatti, Samuli, Jermy, Bradley, Ruotsalainen, Sanni, Kristiansson, Kati, Koskelainen, Sami, Perola, Markus, Donner, Kati, Kivinen, Katja, Palotie, Aarno, Kaunisto, Mari, Julienne, Hanna, Aschard, Hugues, Deleuze, Jean-Francois, Debette, Stephanie, Tregouet, David-Alexandre, Abel, Laurent, Henches, Léo, Lefloch, Edith, Claire, Dandine-Roulland, Sakuntabhai, Anavaj, Bourgeron, Thomas, Olaso, Robert, Daian, Delphine Bacq, Pellegrin, Isabelle, Casanova, Jean-Laurent, Cobat, Aurélie, Jouanguy, Emmanuelle, Zhang, Qian, Ghosn, Jade, Mentré, France, Laouénan, Cédric, Tubiana, Sarah, Chirouze, Catherine, Quintana-Murci, Luis, Patin, Etienne, Duffy, Darragh, Boland, Anne, Carreras, Anna, Galván-Femenía, Iván, Farré, Xavier, Cortés, Beatriz, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Garcia-Aymerich, Judith, Castaño-Vinyals, Gemma, Dobaño, Carlota, van Heel, David A., Hunt, Karen A., Trembath, Richard C., Jacobs, Benjamin Meir, Huang, Qin Qin, Martin, Hilary C., Mason, Dan, Trivedi, Bhavi, Wright, John, Munisamy, Malathy, Finer, Sarah, Griffiths, Christopher J., McCarthy, Mark I., Rosenberger, Carrie, Lee, Jong Eun, Chang, Diana, Hammer, Christian, Hunkapiller, Julie, Mahajan, Anubha, Pendergrass, Rion, Sucheston-Campbell, Lara, Yaspan, Brian, Lee, Hyun Soo, Shin, Eunsoon, Jang, Hye Yoon, Kim, Sunmie, Kym, Sungmin, Kim, Yeon-Sook, Jeong, Hyeongseok, Kwon, Ki Tae, Kim, Shin-Woo, Kim, Jin Yong, Jang, Young Rock, Kim, Hyun ah, Lee, Ji yeon, Lee, Jeong Eun, Lee, Shinwon, Choe, Kang-Won, Kang, Yu Min, Jee, Sun Ha, Jung, Keum Ji, Park, Hyun-Young, Kim, Bong-Jo, Kim, Young Jin, Hwang, Mi Yeong, Yoon, Kyungheon, Pairo-Castineira, Erola, Rawlik, Konrad, Caulfield, Mark J., Baillie, J. Kenneth, Griffiths, Fiona, Bretherick, Andrew D., Stuckey, Alex, Odhams, Christopher A., Walker, Susan, Russell, Clark D., Malinauskas, Tomas, Wu, Yang, Shen, Xia, Elliott, Katherine S., Morrice, Kirstie, Keating, Sean, Wang, Bo, Rhodes, Daniel, Klaric, Lucija, Zechner, Marie, Parkinson, Nick, Fawkes, Angie, Murphy, Lee, Vitart, Veronique, Wilson, James F., Yang, Jian, Scott, Richard H., Moutsianas, Loukas, Law, Andy, Begg, Colin, Hendry, Sara Clohisey, Hinds, Charles, Horby, Peter, Knight, Julian, Ling, Lowell, Maslove, David, McAuley, Danny, Millar, Johnny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Ponting, Chris P., Rowan, Kathy, Semple, Malcolm G., Shankar-Hari, Manu, Summers, Charlotte, Walsh, Timothy, Pan, Jacqueline, Grau, Neus, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Bociek, Aneta, Campos, Sara, Arbane, Gill, Ostermann, Marlies, Cha, Mina, DAmato, Fabiola, Kosifidou, Eirini, Lorah, Shelley, Morera, Kyma, Brady, Laura, Hugill, Keith, Henning, Jeremy, Bonner, Stephen, Headlam, Evie, Jones, Jessica, List, Abigail, Morley, Joanne, Welford, Amy, Kamangu, Bobette, Ratnakumar, Anitha, Shoremekun, Abiola, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavros, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Zongo, Olivier, Wood, Suzanne, Zak, Anne, Collier, David, Mundy, Manuela, Thompson, Christopher, Pritchard, Lisa, Gellamucho, Minnie, Cartlidge, David, Bandla, Nageswar, Bailey, Lucy, Davies, Michelle, Delaney, Jane, Scott, Leanne, Abdelrazik, Marwa, Alasdair, Frater, Carter, David, Elhassan, Munzir, Ganesan, Arunkumar, Jenkins, Samuel, Lamond, Zoe, Purohit, Dharam, Rohit, Kumar, Saleem, Malik, Wall, Alanna, Xavier, Kugan, Bakthavatsalam, Dhanalaksmi, Gehad, Kirolos, Gnanapragasam, Pakeerathan, Jain, Kapil, Jain, Swati, Malik, Abdul, Pappachan, Naveen, Moreno-Cuesta, Jeronimo, Haldeos, Anne, Vincent, Rachel, Oziegb, Maryjane, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, Knighton, Abigail, Nayak, Monalisa, Pappa, Evita, Saha, Rohit, Saha, Sian, Dodd, Andrew, O’Reilly, Kevin, McPhail, Mark, Clarey, Emma, Noble, Harriet, Smith, John, Coghlan, Phoebe, Brett, Stephen, Gordon, Anthony, Templeton, Maie, Antcliffe, David, Banach, Dorota, Darnell, Sarah, Fernandez, Ziortza, Jepson, Eleanor, Mohammed, Amal, Rojo, Roceld, Arias, Sonia Sousa, Gurung, Anita Tamang, Wong, Jenny, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Waite, Alicia A. C., Williams, Karen, Waugh, Victoria, Welters, Ingeborg, Emblem, Jessica, Norris, Maria, Shaw, David, Bashyal, Archana, Beer, Sally, Hutton, Paula, McKechnie, Stuart, Davidson, Neil, Mathew, Soya, Readion, Grace, Ryu, Jung, Wilson, Jean, Agrawal, Shruti, Elston, Kay, Jones, Megan, Meaney, Eoghan, Polgarova, Petra, Elbehery, Muhammad, Daubney, Esther, Ng, Anthony, Marshall, Jocelyn, Pathan, Nazima, Stroud, Katerina, White, Deborah, Andrew, Angela, Ashraf, Saima, Clark, Amy, Dent, Martin, Langley, Margaret, Peters, Cecilia, Ryan, Lucy, Sampson, Julia, Wei, Shuying, Baddeley, Alice, Meredith, Megan, Morris, Lucy, Gibbons, Alexandra, McLoughlin, Lisa, Delgado, Carlos Castro, Clark, Victoria, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Harrison, Abiola, Hurt, William James, Kanu, Rebecca, Kinch, Ashley, Leaver, Susannah, Lisboa, Ana, Mathew, Jisha, Patel, Kamal, Saluzzio, Romina Pepermans, Rawlins, John, Samakomva, Tinashe, Shah, Nirav, Sicat, Christine, Texeira, Joana, Queiroz, Joana Gomes De, Gloria, Edna Fernandes Da, Maccacari, Elena, Yun, Nikki, Manna, Soumendu, Farnell-Ward, Sarah, Maizcordoba, Maria, Thanasi, Maria, Ali, Hawakin Haji, Hastings, Janice, Grauslyte, Lina, Hussain, Musarat, Ruge, Bobby, King, Sam, Pogreban, Tatiana, Rosaroso, Lace, Smith, Helen, Phull, Mandeep-Kaur, Adams, Nikkita, Franke, George, George, Aparna, Salciute, Erika, Wong, Joanna, Dunne, Karen, Flower, Luke, Sharland, Emma, Sra, Sukhmani, Andrew, Gillian, Callaghan, Marie, Barclay, Lucy, Marshall, Lucy, Amamio, Maria, Birch, Sophie, Briton, Kate, Clark, Sarah, Doverman, Katerine, Hope, Dave, Mcculloch, Corrienne, Simpson, Scott, Singleton, Jo, Fernandez, Rita, Allen, Meryem, Baptista, David, Crowe, Rebecca, Fox, Jonathan, Khera, Jacyntha, Loveridge, Adam, McKenley, India, Morino, Eriko, Naranjo, Andres, O’Connor, Denise, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Herdman-Grant, Rosie, Joseph, Anna, Nown, Angela, Rose, Steve, Pogson, David, Boxall, Helen, Brimfield, Lutece, Claridge, Helen, Daly, Zoe, George, Shenu, Gribbin, Andrew, Cheema, Yusuf, Cutler, Sean, Richards, Owen, Roynon-Reed, Anna, Cherian, Shiney, Heron, Anne Emma, Williams, Gemma, Szakmany, Tamas, Waters, Abby, Collins, Kim, Dunhill, Jill, Jones, Ffion, Morris, Rebecca, Ship, Lucy, Cardwell, Amy, Ali, Syamlan, Bhatterjee, Ravi, Bolton, Rachel, Chukkambotla, Srikanth, Coleman, Dabheoc, Dalziel, Jack, Dykes, Joseph, Fine, Christopher, Gay, Bethan, Goddard, Wendy, Goodchild, Drew, Harling, Rhiannan, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Matt, Roseanna, Ryan-Smith, Janet, Saad, Samuel, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Kazi, Aayesha, Smith, Matthew, Collier, Heather, Davison, Chloe, Duberley, Stephen, Hargreaves, Jeanette, Hartley, Janice, Patel, Tahera, Smith, Ellen, Kent, Alissa, Goodwin, Emma, Zaki, Ahmed, Tibke, Clare, Hopkins, Susan, Gerrard, Hywel, Jackson, Matthew, Bennett, Sara, Marsh, Liane, Mills, Rebecca, Bell, Jessica, Campbell, Helen, Dawson, Angela, Dodds, Steve, Duffy, Stacey, Gallagher, Lisa, McCafferty, Gemma, Short, Stacey, Smith, Tracy, Thomas, Kirsty, Walker, Claire, Reynolds, Jessica, Yates, Bryan, McKie, Hayley, Panteli, Maria, Thompson, Maria, Waddell, Gail, Beger, Sarah De, Abraheem, Azmerelda, Dunmore, Charlie, Girach, Rumanah, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Brearey, Stephen, Burchett, Caroline, Cawley, Kathryn, Faulkner, Maria, Jeffrey, Helen, Bamford, Peter, Shaikh, Firdaus, Slack, Lauren, Davies, Angela, Brooke, Hollie, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Sandhu, Rajdeep, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Buckley, Sarah, Sloan, Brendan, Rose, Alastair, Major, Amy, Metcalfe, Alexandra, Almaden-Boyle, Christine, Austin, Pauline, Chapman, Susan, Eros, Alexandre, Cabrelli, Louise, Cole, Stephen, Whyte, Clare, Casey, Matt, Bafitis, Vasileios, Tsinaslanidis, George, George, Cassandra, Khade, Reena, Black, Christopher, Ashok, Sundar Raj, Farley, Sean, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Williams, Marie, Newey, Luke, Toghill, Hannah, Lewis, Sophie, Rees, Tabitha, Battle, Ceri, Baker, Mark, Travers, Jenny, Chesters, Karen, Baxter, Nicola, Arnott, Andrew, McCreath, Gordan, McParland, Christopher, Rooney, Laura, Sim, Malcolm, Henderson, Steven, Abel, Lynn, Dalton, Carol, Kennedy-Hay, Sophie, O’Donohoe, Lynn, O’Hare, Megan, Orlikowska, Izabela, Parker, Natasha, McNeela, Fiona, Lyle, Amanda, Hughes, Alistair, Radhakrishnan, Jayachandran, Gibson, Sian, Bancroft, Hollie, Bellamy, Mary, Daglish, Jacqueline, Kadiri, Salma, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Peterkin, Zhane, Scriven, James, Carmody, Margaret, Cottle, Juliet, Peasgood, Emily, de Gordoa, Laura Ortiz-Ruiz, Phillips, Claire, Skinner, Denise, Cinquina, Zoe, Howard, Kate, Joy, Rosie, Roche, Samantha, Birkinshaw, Isobel, Carter, Joseph, Ingham, Jo, Marshall, Nicola, Pearson, Harriet, Scott, Zoe, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Bamford, Amy, Hull, Diana, Ahmadhaider, Nafeesah, Bates, Michelle, McGhee, Christopher, Ellis, Hannah, Howe, Gwenllian Sera, Singh, Jayaprakash, Stroud, Natalie, Roche, Lisa, Lynch, Ceri, Deacon, Bethan, Pothecary, Carla, Smeaton, Justyna, Agravante, Kevin, Krishnamurthy, Vinodh, Diaba, Cynthia, John, Lincy, Lim, Lai, Jha, Rajeev, Egan, Jasmine, Felton, Timothy, Glasgow, Susannah, Padden, Grace, Choudhr, Ozerah, Bradley-Potts, Joanne, Moss, Stuart, Lingeswaran, Saejohn, Alexander, Peter, Brandwood, Craig, Fiouni, Sofia, Ward, Luke, Allen, Schvearn, Shaw, Jane, Smith, Christopher, Adanini, Oluronke, Collins, Rebecca, Msiska, Maines, Ofori, Linda, Bhatia, Nikhil, Dolan, Hayley, Brunton, Mark, Caterson, Jess, Coles, Holly, Keating, Liza, Tilney, Emma, Jacques, Nicola, Frise, Matthew, Armistead, Jennifer, Bartley, Shauna, Bhuie, Parminder, Rai, Sabi, Tomkova, Gabriela, Greer, Sandra, Shuker, Karen, Tridente, Ascanio, Dobson, Emma, Hunt, Jodie, Tully, Redmond, Dearden, Joy, Drummond, Andrew, Kamath, Prakash, Bullock, Emily, Mulcahy, Michelle, Munt, Shelia, O’Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Scott, Chloe, Winnard, Sarah, Hasni, Nurkamalia, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Beavis, Sarah, Bishop, Lauren, Cart, Cindy, Dale, Katie, Kelly-Baxter, Mary, Mendelski, Adam, Moakes, Emma, Smith, Rheanna, Woodward, Jan, Wright, Stephanie, Allan, Angela, Botello, Adriana, Liew, Jade, Medhora, Jasmine, Trumper, Erin, Savage, Felicity, Scott, Teresa, Place, Marc, Kaye, Callum, Benyon, Sarah, Marriott, Suzie, Park, Linda, Quinn, Helen, Skyes, Daisy, Zitter, Lily, Baines, Kizzy, Gordon, Elizabeth, Keenan, Samantha, Pitt, Andrew, Duffy, Katharine, Ireland, Jane, Semple, Gary, Turner, Lynne, Cathcart, Susanne, Rimmer, Dominic, Puxty, Alex, Puxty, Kathryn, Hurst, Andrew, Miller, Jennifer, Speirs, Susan, Walker, Lauren, Bradshaw, Zena, Brown, Joanna, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Warden, Scott, Beasley, Alanna, Stoddard, Emma, Benham, Leonie, Cupitt, Jason, Caswell, Melanie, Elawamy, Lisa, Wignall, Ashleigh, Roberts, Belinda, Golding, Hannah, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Golder, Kim, Jones, Oliver, Cusack, Rebecca, Bolger, Clare, Burnish, Rachel, Carter, Michael, Jackson, Susan, Salmon, Karen, Biss, Jonathan, Aquino, Maia, Croft, Maria, Frost, Victoria, White, Ian, Govender, Keshnie, Webb, Natasha, Stapleton, Liana, Wells, Colin, Nikitas, Nikitas, Sanchez - Rodriguez, Ana, Spencer, Kayleigh, Stowe, Bethan, Izzard, Yvonne, Poole, Michelle, Monnery, Sonja, Trotman, Sallyanne, Beech, Valerie, Combes, Edward, Joefield, Teishel, Covernton, Patrick, Savage, Sarah, Woodward, Elizabeth, Camsooksai, Julie, Reschreiter, Henrik, Barclay, Charlotte, DeAth, Yasmin, Dube, Judith, Humphrey, Charlotte, Jenkins, Sarah, Langridge, Emma, Milne, Rebecca, Wadams, Beverley, Woolcock, Megan, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, James, MacGoey, Patrick, O’Neil, Pauline, Price, Richard, Sundaram, Radha, Rodden, Natalie, Thomson, Nicola, Rooney, Kevin, Currie, Susan, Henderson, Philip, Ogg, Bethan, Whiteley, Simon, Wilby, Liz, Long, Kate, Matthew, Shailamma, Salada, Sheila, Trott, Susan, Watts, Sarah, Friar, Zoe, Speight, Abigail, Bastion, Victoria, Chandna, Humza, Djeugam, Brice, Haseeb, Muhammad, Kent, Harriet, Lubimbi, Gamu, Murdoch, Sophie, Thomas, Alastair, David, Beena, Lorusso, Rachel, Vochin, Ana, Penacerrada, Melchizedek, Wulandari, Retno, Heath, Charlotte, Jakkula, Srinivas, Morris, Anna, Ahmed, Ashar, Nune, Arvind, Buttriss, Claire, Whitaker, Emma, Davey, Miriam, Golden, David, Acklery, Amy, Fernandes, Fabio, Seaman, Bec, Earl, Victoria, Collins, Amy, Khaliq, Waqas, Adam, Rachel, Treus, Estefania, Holland, Sarah, Alfonso, Jordan, Blackledge, Bethan, Bruce, Michelle, Durrans, Laura Jayne, Eltayeb, Ayaa, Harris, Jade, Hey, Samuel, Hruska, Martin, Lamb, Thomas, Rothwell, Joanne, Fitzgerald, Adele, Lindergard, Gabriella, T-Michael, Helen, Duncan, Tracey, Baxter-Dore, Sharon, Cooper, Lisa, Fox, Claire, Guerin, Jacinta, Hodgkiss, Tracey, Connolly, Karen, McAlinden, Paul, Bridgett, Victoria, Fearby, Maggie, Gulati, A., Hanson, Helen, Kelly, Sinead, McCormack, Louise, Nixon, Rachel, Robinson, Philip, Slater, Victoria, Stephenson, Elaine, Webster, Andrea, Webster, K., Hays, Carole, Hudson, Anne, Patel, Bijal, Clement, Ian, Davis, John, Francis, Sarah, Jerry, Douglas, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Cabral-Ortega, Llucia, Hines, Matthew, Martinson, Victoria, Stones, Elizabeth, Winter, Karen, Barrow, Esther, Wylie, Katharine, Baines, Deborah, Birchall, Katie, Kolakaluri, Laurel, Clark, Richard, Sukumaran, Anila, Barker, Melanie, Paripoorani, Deborah, Smith, Lara, Taylor, Charlotte, Downes, Charlotte, Hayman, Melanie, Riches, Katie, Daniel, Priya, Subramanian, Deepak, Holding, Kathleen, Hilton, Mary, Mcdonald, Carly, Richardson, Georgina, Halladay, Georgia, Harding, Peter, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Parker, Robert, Lloyd, Michaela, Smith, Leanne, Kelly, Charlie, Lazo, Maria, Neal, Alan, Walton, Olivia, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Callam, Sara, Hudig, Lisa, Keshet-Price, Jocelyn, Stammers, Katie, Convery, Karen, Randell, Georgina, Fottrell-gould, Deirdre, Mwaura, Esther, Sutherland, Sara-Beth, Stewart, Richard, Mew, Louise, Wren, Lynn, Thrasyvoulou, Laura, Willis, Heather, Hopkins, Bridget, Lenton, Daniel, Roberts, Abigail, Bokhari, Maria, Lucas, Rachael, McCormick, Wendy, Ritzema, Jenny, Linnett, Vanessa, Sanderson, Amanda, Wild, Helen, Flanagan, Rebecca, Hull, Robert, Rhead, Kat, McKenna, Emma, Hughes, Gareth, Anderson, Jennifer, Jones, Kelly, Latham, Scott, Riley, Heather, Coulding, Martina, Clark, Martyn, McCormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Jude, Edward, Kilroy, Susan, Apetri, Elena, Basikolo, Cathrine, Catlow, Laura, Collis, Matthew, Doonan, Reece, Harvey, Alice, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, McMorrow, Liam, Michael, Angiy, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Dark, Paul, Charles, Bethan, McLaughlan, Danielle, Slaughter, Melanie, Horner, Dan, Marsden, Tracy, Andrews, Joyann, Beech, Emily, Akinkugbe, Olugbenga, Bamford, Alasdair, Belfield, Holly, Jones, Gareth A. L., McHugh, Tara, Meghari, Hamza, Ray, Samiran, Tomas, Ana Luisa, O’Neill, Lauran, Peters, Mark, Bell, Michael, Benkenstein, Sarah, Chisholm, Catherine, Davies, Charlene, Kupiec, Klaudia, Payne, Caroline, Halls, Joanna, Blakemore, Hayley, Goff, Elizabeth, Hayes, Kati, Smith, Kerry, Stephens, Deanna, Worner, Ruth, Borislavova, Borislava, Faulkner, Beverley, Thomas, Matt, Cookson, Ruth, Gendall, Emma, Larman, Georgina, Pope, Rebecca, Smalira, Artur, Priestley, Victoria, Cosier, Tracey, Millen, Gemma, Rand, James, Schumacher, Natasha, Sandhar, Roxana, Weston, Heather, Richardson, Neil, Cooper, Lucy, Jones, Cathy, Huang, Ya-Wen Jessica, Jacob, Reni, Denmade, Craig, Mcintyre, Lewis, Trodd, Dawn, Martin, Jane, Watson, Geoff, Bevan, Emily, Wreybrown, Caroline, Bano, Shereen, Bellwood, Ruth, Bentley, Michael, Bromley, Matt, Gurr, Lucy, Ledgard, Camilla, McGowan, Janet, Pye, Kate, Sellick, Kirsten, Stacey, Amelia, Warren, Deborah, Wilkinson, Brian, Akeroyd, Louise, Shafique, Huma, Morgan, James, Shorter, Susan, Swinger, Rachel, Waters, Emily, Lawton, Tom, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Davies, Llinos, Easton, Jack, Kumar, Sumit, Lean, Richard, Mackay, Callum, Pugh, Richard, Qiu, Xinyi, Rees, Stephanie, Scanlon, Jeremy, Lewis, Joanne, Menzies, Daniel, Bolger, Annette, Davies, Gwyneth, Davies, Jennifer, Garrod, Esther, Jones, Helen, Manley, Rachel, Williams, Hannah, Frankham, Jordan, Pitts, Sally, White, Nigel, Branney, Debbie, Tiller, Heather, Efford, Georgia, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Bewley, Jeremy, Coleman, Christina, Corcoran, Katie, Morano, Eva Maria Hernandez, Shiel, Rachel, Webster, Denise, Bonnici, Josephine, Daniel, Eleanor, Dell, Abbie, Kent, Melanie, Wilkinson, Ami, Brown, Ellen, Kay, Andrea, Campbell, Suzanne, Cowton, Amanda, Birt, Mark, Greenaway, Vicki, Potts, Kathryn, Hutton, Clare, Shepperson, Andrew, Forsey, Miranda, Nicholson, Alice, Vertue, Mark, Riches, Joanne, Kaliappan, Agilan, Nicholson, Anne, MacCallum, Niall, Raith, Eamon, Bercades, Georgia, Hass, Ingrid, Brealey, David, Martir, Gladys, Reyes, Anna, Smyth, Deborah, Zapatamartinez, Maria, Alvaro, Ana, Jetha, Champa, Ma, Louise, Booker, Lauren, Mostoles, Loreta, Pratley, Anezka, Altabaibeh, Abdelhakim, Parmar, Chetan, Gilbert, Kayleigh, Ferguson, Susie, Shepherd, Amy, Morris, Sheila, Baruah, Rosie, Lloyd, Georgina, Bell, Stephanie, Rivers, Vanessa, Purewal, Bally, Hammerton, Kate, Anderson, Susan, Birch, Janine, Collins, Emma, Oleary, Ryan, Cornell, Sarah, Jarmain, Jordan, Rogerson, Kimberley, Wakinshaw, Fiona, Woods, Lindsey, Rostron, Anthony, Elcioglu, Zeynep, Roy, Alistair, Bell, Gillian, Dickson, Holly, Wilcox, Louise, Katary, Amro, English, Katy, Hutter, Joanne, Pawley, Corinne, Doble, Patricia, Shovelton, Charmaine, Vaida, Marius, Purnell, Rebecca, Thomas, Ashly, Cagova, Lenka, Fofano, Adama, Holcombe, Helen, Mitchell, Alice Michael, Mwaura, Lucy, Praman, KrithivasanÂ, Garnr, Lucie, Mepham, Sue, Paques, Kitty, Vuylsteke, Alain, Mackie, Jennifer, Pearn, Carmen, Zamikula, Julie, Nyirenda, Maggie, Capozzi, Lisa, Reece-Anthony, Rosie, Noor, Hazma, Nilo, Alfa Cresia, Grove, Michelle, Daniel, Amelia, Finn, Joanne, White, Nikki, Saha, Rajnish, Badal, Bibi, Ixer, Karen, Duffin, Donna, Player, Ben, Hill, Helen, Cole, Jade, Brooks, Jenny, Davies, Rhys, Hunt, Lauren, Thomas, Emma, Williams, Angharad, Oblak, Metod, Thankachen, Mini, Irisari, Jamie, Sayan, Amrinder, Popescu, Monica, Finch, Cheryl, Jamieson, Andrew, Quinn, Alison, Cooper, Joshua, Liderth, Sarah, Waddington, Natalia, Burn, Iona, Manso, Katarina, Penn, Ruth, Tebbutt, Julie, Thornton, Danielle, Winchester, James, Hambrook, Geraldine, Shanmugasundaram, Pradeep, Craig, Jayne, Simpson, Kerry, Higham, Andrew, Sibbett, Louise, Paine, Sheila, Reed, Annabel, Conyngham, Jo-Anna, Mupudzi, Mcdonald, Thomas, Rachel, Wright, Mary, Griffin, Denise, Partridge, Richard, Corral, Maria Alvarez, Muchenje, Nycola, Sitonik, Mildred, Butler, Aaron, Folkes, Linda, Fox, Heather, Gardner, Amy, Helm, David, Hobden, Gillian, King, Kirsten, Margalef, Jordi, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Baird, Yolanda, Gomez, Raquel, Martin, Darren, Hodgson, Luke, Corin, Clinton, Sidall, Erikka, Szabo, Densie, Floyd, Sharon, Davies, Hannah, Austin, Karen, Kelsall, Olivia, Wood, Hannah, Cornell, Thomas, Ralph, Kate, Bean, Sarah, Burt, Karen, Spivey, Michael, Richards, Carol, Tedstone, Rachel, Carmody, Siobhain, Zhao, Xiaobei, Page, Valerie, Guanco, Mark Louie, Hoxha, Elvira, Zorloni, Camilla, Dean, Charlotte, Jones, Emma, Carter, Emma, Dunn, Joshua, Kong, Thomas, Mahenthran, Mervin, Marsh, Chris, Holland, Maureen, Keenan, Natalie, Mahmoud, Mohamed, Lyons, Marc, Wassall, Helen, Young, Meghan, Bradley, Paul, Burda, Dorota, Donlon, Sinead, Harden, Lesley, Harris, Celia, Mayangao, Irving, Montaser, Rugia, Mtuwa, Sheila, Piercy, Charles, Smith, Eleanor, Stone, Sarah, Verula, Jerik, Blackman, Helen, Marriott, Cheryl, Michalak, Natalia, Creagh-Brown, Ben, Salberg, Armorel, Boyer, Naomi, Pristopan, Veronika, Maynard, Victoria, Walker, Rachel, Hormis, Anil, Collier, Dawn, Graham, Cheryl, McCormick, Jake, Warrington, Jake, Cosgrove, Denise, McFarland, Denise, Ratcliffe, Judith, Charnock, Rob, Wynter, Inez, Gill, Mandy, Kirk, Jill, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Jardine, Catherine, Hay, Alasdair, Williams, Dewi, Durga, Latha, Hibbert, Meg, Kennard-Holden, Gareth, Woodford, Chrsitopher, Tetla, Dariusz, Price, Alicia, Thomas, Alice, Thorpe, Chris, Knights, Ellen, Ward, Donna, Laha, Shondipon, Verlander, Mark, Williams, Alexandra, Prout, Rachel, Langton, Helen, Watters, Malcolm, Hunt, Charlotte, Novis, Catherine, Arif, Sarwat, Cunningham, Amy, Hewitt, Claire, Hindale, Julia, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susie, Tavares, Silivia, Barber, Russell, Hilldrith, Annette, Hubbard, Kelly, Egginton, Dawn, Clark, Michele, Purvis, Sarah, Sinclair, Simon, Collins, Vicky, Landeg, Bethan, Sell, Craig, Coetzee, Samantha, Gales, Alistair, Otahal, Igor, Icke, Becky, Raj, Meena, Williams, Caroline, Williams, Jill, Hill, Lucy, Kayani, Abdul, Masunda, Bridgett, Gondo, Prisca, Atayeva, Nigara, Cruz, Carina, Pattison, Natalie, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Newton, Maria, Al-Moasseb, Hassan, Behan, Teresa, Player, Jasmine, Stead, Rachael, Mitra, Atideb, Nauyokas, Kirsty, Humphreys, Sally, Cockerill, Helen, Tampsett, Ruth, Postovalova, Evgeniya, Coventry, Tina, McGregor, Amanda, Fowler, Susan, Macmahon, Mike, Cochrane, Patricia, Pirie, Sandra, Hanley, Sarah, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Ishaq, Tahira, Kelly, Diane, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Merwaha, Ekta, Nortcliffe, Tonicha, Shaw, Lisa, Shaw, Ryan, Wood, Tracy, Bayo, Lee-Ann, Usher, Miranda, Wilson, Alison, Kitson, Ross, Pinnell, Jez, Robinson, Matthew, Boltwood, Kaitlin, Birch, Jenny, Bough, Laura, Tutton, Rebecca, Winter-Goodwin, Barbara, Goodsell, Josie, Taylor, Kate, Williams, Patricia, Williams, Sarah, Cave, Ashleigh, Rees, James, Imeson-Wood, Janet, Smith, Jacqueline, Amin, Vishal, Karthik, Komala, Kausar, Rizwana, Anastasescu, Elena, Reid, Karen, Anumakonda, Vikram, Stoddart, Ella, Demetriou, Carrie, Eckbad, Charlotte, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, White, Katie, Hierons, Sarah, Kelly, Fiona, Serrano-Ruiz, Alfredo, Evans, Gabrielle, Nicol, Liz, Wilkins, Joy, Hulacka, Kim, Debreceni, Gabor, Brown, Alison, Crickmore, Vikki, Hill, Kay, Kannan, Thogulava, Dagutao, Zenaida, Beesley, Kate, Lewis, Alison, Perry, Jess, Antony, Sherly, Board, Sarah, Buckley, Clare, Pippard, Lucy, Tanate, Alfonso, Wood, Diane, Kubisz-Pudelko, Agnieska, Gouda, Ayman, Auld, Fiona, Donnachie, Joanne, Murdoch, Euan, Prentice, Lynn, Runciman, Nikole, Senaratne, Dhaneesha, Short, Abigail, Sweeney, Laura, Symon, Lesley, Todd, Anne, Turner, Patricia, McCann, Erin, Salutous, Dario, Edmond, Ian, Whitelaw, Lesley, Bland, Yvonne, Kajtor, Istvan, Kavanagh, Lisa, Singler, Karen, Linfield-Brown, George, Moore, Luke Stephen Prockter, Vizcaychipi, Marcela, Martins, Laura, Moore, Luke, Bull, Rhian, Carungcong, Jaime, Allen, Louise, Beranova, Eva, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turney, Sharon, Hazelton, Tracy, Tutt, Gabriella, Arora, Mansi, Turki, Salah, Sinfield, Emily, Deery, Joanne, Ramos, Hazel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Thwaites, Vicky, Patel, Brijesh, Kamal, Liyanage, Zborowski, Anelise Catelan, Coe, Ryan, Anderson, Madeleine, Beadle, Jane, Coates, Charlotte, Collins, Katy, Crowley, Maria, Johnson, Laura, King, Laura, Paramsothy, Remi, Sargeant, Janet, Silva, Pedro, Stuart, Carmel, Taylor, June, Tyl, David, Wakefield, Phillipa, Kamundi, Charlotte, Olufuwa, Olumide, Belagodu, Zakaulla, Gherman, Anca, Oakley, Naomi, Allan, John, Geary, Tim, Meikle, Alistair, O’Brien, Peter, Wood, Stephen, Clark, Andrew, Houston, Gordon, Black, Karen, Clarkson, Michelle, D’Sylva, Stuart, Morrison, Alan, Norman, Kathryn, Taylor, Margaret, Clements, Suzanne, Cohrane, Catriona, Gonzalez, Nora, Strachan, Dominic, Beith, Claire, Moar, Kirsten, Anderson, Peter, Archer, Katie, Burtenshaw, Andrew, Clayton, Sarah, Cother, Naiara, Cowley, Nicholas, Davis, Caroline, Digby, Stephen, Durie, Alison, Harrison, Alison, Low, Emma, McAlindon, Michael, McCurdy, Alex, Morgan, Aled, Rankin, Tobias, Thrush, Jessica, Tranter, Helen, Vigurs, Charlie, Wild, Laura, Murphy, Lorna, Smythe, Michelle, Brickell, Kathy, Ali, Inthakab Ali Mohamed, Beaumont, Karen, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Coton, Zoe, Joshy, Aricsa, Blunt, Mark, Curgenven, Hollie, Botfield, Liam, Dexter, Catherine, Kuravi, Aditya, Butler, Joanne, Chadwick, Robert, Ranga, Poonam, Richardson, Lisa, Virgilio, Emma, Anwer, Maddiha, Garg, Atul, Botfield, Donna, Marriott, Xana, Stewart, Keely, Mullan, Dee, Gaylard, Jane, Nowak, Justyna, Jones, Sian, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Lancaster, Nicola, Matthews, Jamie, Wray, Gemma, Inweregbu, Ken, Cutts, Sarah, Miller, Katharine, Brady, Ailbhe, Chan, Rebekah, McIvor, Shane, Prady, Helena, Mathew, Bijoy, Little, Jeff, Furniss, Tim, Wright, Chris, King, Bernadette, Wasson, Christopher, O’Neill, Aisling, Turley, Christine, McGuigan, Peter, Collins, Erin, Finn, Stephanie, Green, Jackie, McAuley, Julie, Nair, Abitha, Quinn, Charlotte, Tauro, Suzanne, Ward, Kathryn, McGinlay, Michael, Reddy, Kiran, Ahmad, Norfaizan, Anderson, Samantha, Barker, Joann, Bauchmuller, Kris, Birchall, Kathryn, Bird, Sarah, Cawthron, Kay, Chetam, Luke, Cole, Joby, Donne, Ben, Foote, David, Ford, Amber, Hanratty, Helena, Harrington, Kate, Hesseldon, Lisa, Housley, Kay, Jackson, Yvonne, Jarman, Claire, Kibutu, Faith, Lenagh, Becky, Macharia, Irene, Masuko, Shamiso, Milner, Leanne, Newell, Helen, Nwafor, Lorenza, Oxspring, Simon, Phillips, Patrick, Raithatha, Ajay, Rowland-Jones, Sarah, Smith, Jacqui, Thompson, Roger, Trower, Helen, Walker, Sara, Watson, James, Wiles, Matthew, Lye, Alison, Willson, Jayne, Mills, Gary, Harris, Sansha, Hartill, Eleanor, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Nolan, Claire, Polgar, Oliver, Prendergast, Claire, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Mahay, Kanta, Reed, Anna, Meyrick, Hayley, Passmore, Heather, Farwell, James, O’Connell, Susan, Gregory, Jane, Barberis, Luigi, Harper, Rosemary, Smith, Tim, Armstrong, Diane, Bowey, Angie, Cowley, Anne, Corner, Andrew, Highgate, Judith, Rutherfurd, Claire, Taylor, Jo-Anne, Goodwin, Sarah, Eapen, Beena, Trim, Fiona, Donnison, Phil, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Kitching, Amy, McParland, Chantal, Packham, Sophie, Hairsine, Brigid, Andreou, Premetie, Hales, Dawn, Mathews, Megha, Patel, Rekha, Barry, Peter, Flint, Neil, Hailstone, Jessica, Ghuman, Navneet, Leonard, Bethany, Lees, Rachel, Butcher, Deborah, Leng, Katy, Butterworth-Cowin, Nicola, O’Sullivan, Susie, Ghosh, Alison, Williams, Emma, Adams, Colene, Agasou, Anita, Arden, Tracie, Beekes, Mandy, Bowes, Amy, Boyle, Pauline, Button, Heather, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, James, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Newman, Julie, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Donaldson, Denise, Capps, Nigel, Cale, Emily, Jose, Sanal, Osbourne, Wendy, Pajak, Susie, Rankin, Jayne, Tonks, Louise, Baird, Tracy, Harkins, Margaret, Ruddy, Jim, West, Joe, Duffield, Joseph, Mallon, Lewis, Smith, Oliver, Smuts, Sara, Campbell, Andy, Davies, Cate, Davies, Sarah, Hughes, Rachel, Jobes, Lisa, Whitehead, Victoria, Watkins, Clare, Bowman, Fiona, Milligan, Barry, McPherson, Liane, Metherell, Stella, Harris, Nichola, Lake, Victoria, Radford, Elizabeth, Smallwood, Andy, Gopal, Shameer, Vassell, Katherine, Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lennon, Liz, Rattray, Austin, Lee, Emma, Jones, Danielle, Parsons, Penny, Attwood, Ben, Jefferson, Paul, Ranganathan, Mohan, Atwal, Inderjit, Campbell, Bridget, Day, Angela, Stagg, Camilla, Haynes, Emma, Ahmed, Cecilia, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Joseph, Sibet, Maqsood, Zahira, Hussain, Samia, Hulme, Jonathan, Domingos, Patience, Kumar, Rita, Purewal, Manjit, Taylor, Becky, Bunni, Lara, Latif, Monica, Jennings, Claire, Jose, Shilu, Marshall, Rebecca, Metryka, Aleksandra, Subramanian, Gayathri, Burgoyne, Adam, Tyler, Amanda, Waldron, Joanne, Hilltout, Paula, Evitts, Jayne, Ward, Geraldine, Bremmer, Pamela, Hawkins, Carl, Jackman, Sophie, Ogorek, Michal, Ashby, Kylie, Thornton, Lorraine, Mercer, Pauline, Halkes, Matthew, Revill, Adam, Saint, Bryony, Fletcher, Jo, Netherton, Kimberley, Chablani, Manish, Kirkby, Amy, Roper, Amanda, Szymiczek, Kinga, Sutherland, Isobel, O’Brien, Linda, Connell, Joanne, Davies, Kim, Lewis, Tracy, Omar, Zohra, Perkins, Emma, Sathe, Sonia, Davies, Ellie, Lyon, Alex, Mapfunde, Isheunesu, Willis, Charlotte, Hitchcock, Rachael, Hall, Kathryn, King, Christopher, Fagan, Andrew, Nazari, Roonak, Worsley, Lucy, Allibone, Suzanne, Kasipandian, Vidya, Patel, Amit, Cutting, Parisa, Genetu, Roman, Mac, Ainhi, Murphy, Anthony, Ward, Sinead, Butt, Fatima, Ayers, Amanda, Harrison, Wendy, Mackintosh, Katherine, North, Julie, Ashton, Lydia, Bi, Rehana, Owen, Samantha, Winmill, Helen, Scholefield, Barney, Blowing, Hannah, Williams, Erin, Duskova, Michaela, Edwards, Michelle, Rees, Alun, Thomas, Helen, Brooks, Jolene, Phipps, Janet, Brooks, Suzanne, Dennis, Catherine, Parris, Vicki, Srikaran, Sinduya, Sukha, Anisha, McGregor, Alistair, Tiongson, Gerlynn, Adams, Katie, Andrew, Benedict, Brayne, Adam, Carter, Sasha, Findlay, Louise, Fisher, Emma, Jackson, Peter, Kaye, Duncan, Parkin, Juliet, Tuckey, Victoria, Hunt, Jane, Love, Nicholas, van Koutrick, Lynne, Hanson, Ashley, Dent, Kathy, Horsley, Elizabeth, Pearson, Sandra, Spencer, Sue, Hutchinson, Dorothy, Potoczna, Dorota, Akhtar, Muhammad Nauman, Cottam, Lisa-Jayne, Sanders, Jack, Garcia, Sara Mingo, pakou, Glykeria, Filipe, Helder, Maharajh, Amitaa, de Neef, Mark, Martin, Daniel, Eastgate, Christine, Teoh, Poh Choo, Barrett, Fiona, Bradley, Clare, Donaldson, Avril, Mascarenhas, Mairi, O’Hara, Marianne, Okeefe, Laura, Clarke, Noreen, Whiteside, Jonathan, Campbell, Rachael, Matheson, Joanna, McDonald, Deborah, Patience, Donna, Rice, Polly, Clapham, Melanie, Mutch, Rachel, Craig, Hannah, Poultney, Una, Burns, Karen, Twiss, Sophie, Barton, Janet, George, Linsha, Harrop, Clare, Mathew, Sherly, Wright, David Justin, Harrison, Rachel, Toohie, Jordan, Chandler, Ben, Turnbull, Alison, Mallinson, Janine, Elliott, Kerry, Wolf-Roberts, Rebecca, Tench, Helen, Hobrok, Maria, Loosley, Ronda, McGuinness, Heather, Sims, Tanya, Afolabi, Deborah, Allison, Kathryn Sian, Anderson, Taya, Dore, Rachael, Jones, Dawn, Rogers, Naomi, Saunderson, Paula, Whitbread, Jennifer, O’Malley, Laura, Rad, Laura, Hawcutt, Daniel, Aldridge, Jonathan, Tolson, Melanie, Garrioch, Sweyn, Tomlinson, Joanne, Grosdenier, Michael, Loader, David, Kapoor, Ritoo, Hector, Gemma, Scherewode, Joslan, Sri-Chandana, Chunda, Stephenson, Lorraine, Marsh, Sarah, Rosa, Arnold Dela, Jhanji, Shaman, Bemand, Thomas, Howle, Ryan, Baikady, Ravishankar Rao, Thomas, Benjamin, Black, Ethel, Tatham, Kate, Gurram, Sambasivarao, Watson, Ekaterina, Quaid, Sheena, Saunderson, Anne, O’Brien, Rachel, Moultrie, Sam, Service, Jen, Cheyne, Clare, Odam, Miranda, Wiliams, Alison, Barnes, Nicky, Csabi, Peter, Rocha, Joana Da, Glynou, Louika, Huffenberger, Amy, Bryant, Jade, Pickard, Amy, Roe, Nicholas, Bellini, Arianna, Mayer, Anton, Burrow, Amy, Colley, Natalie, Evans, Jayne, Howlett, Alex, Khalifeh, Zeinab, Pryce, Jerldine, Gorman, Claire, Brady, Rebecca, Timlick, Elizabeth, Antoine, Pierre, Gupta, Abhinhav, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tucci, Arianna, Tariq, Ambreen, Tagliavini, Emma, Ramsay, Becky, Fidler, Katy, Donnelly, Kevin, Hollis, Rebecca, Barr, Jocelyn, Boyd, Elizabeth, Irvine, Val, Shelley, Ben, Buckley, Julie, Hamilton, Charlene, Valdeavella, Kathryn, Bircham, Sarah, Liggett, Steven, Patil, Anand, Siddiq, Afshan, Goddard, Peter, Donovan, Sally, Zainy, Tala, Maleady-Crowe, Fiona, Todd, Linda, Salehi, Shahla, Elgar, Greg, Chan, Georgia, Arumugam, Prabhu, Patch, Christine, Rendon, Augusto, Bentley, David, Kingsley, Clare, Fowler, Tom A., Elliott, Paul, Tenesa, Albert, Aitkin, Emma, Aravindan, Latha, Armstrong, Ruth, Biggs, Heather, Boz, Ceilia, Brown, Adam, Chikowore, Primmy, Coutts, Audrey, Coyle, Judy, Cullum, Louise, Das, Sukamal, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Finernan, Paul, Fourman, Max Head, Furlong, Anita, Furniss, James, Gallagher, Bernadette, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Hamilton, Debbie, Hendry, Ross, Kearns, Naomi, Law, Dawn, Law, Rachel, Law, Sarah, Lidstone-Scott, Rebecca, Lauder, Christen, Macgillivray, Louise, Maclean, Alan, Mal, Hanning, McCafferty, Sarah, Mcmaster, Ellie, Meikle, Jen, Moore, Shona C., Murphy, Sheena, Mybaya, Hellen, Oosthuyzen, Wilna, Zheng, Chenqing, Chen, Jiantao, Paterson, Trevor, Tucker, Petra, Schon, Katherine, Stenhouse, Andrew, Das, Mihaela, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Turtle, Lance, Wackett, Tony, Ward, Mairi, Weaver, Jane, Wrobel, Nicola, Rakitko, Alexander, Ilinsky, Valery, Yermakovich, Danat, Popov, Iaroslav, Chernitsov, Alexander, Kovalenko, Elena, Vergasova, Ekaterina, Prokhorov, Alexandr, Krasnenko, Anna, Plotnikov, Nikolay, Stetsenko, Ivan, Kim, Anna, Cirulli, Elizabeth T., Schiabor Barrett, Kelly M., Bolze, Alexandre, White, Simon, Washington, Nicole L., Lu, James T., Riffle, Stephen, Tanudjaja, Francisco, Wang, Xueqing, Ramirez, Jimmy M., Leonetti, Nicole, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Grzymski, Joseph J., Joshi, Madhvi N., Dixit, Raghav D., Shah, Pranay K., Upadhyay, Kamlesh J., Chuhan, Naresh T., Desai, Kairavi J., Shah, Meenakshi R., Modi, Bhavesh, Joshi, Chaitanya G., Pandit, Ramesh J., Singh, Indra, Ansari, Afzal I., Raval, Janvi N., Patel, Zarna Z., Moreno-Estrada, Andres, Vázquez-Pérez, Joel Armando, Castillejos-López, Manuel, Aquino-Gálvez, Arnoldo, Shamah-Levy, Teresa, Ávila-Arcos, María C., Luna, María Teresa Tusié, Hidalgo-Miranda, Alfredo, Barberena-Jonas, Carmina, Quinto-Cortés, Consuelo D., Ávila-Arcos, Marco Antonio, Huerta-Chagoya, Alicia, García-García, Lourdes, Barnetche, Jesús Martinez, Alpuche-Aranda, Celia, Rivera, Juan A., Gutiérrez, Tonatiuh Barrientos, Ochoa-Guzmán, Ana, Ordoñez-Sánchez, Maria Luisa, Segura-Kato, Yayoi, Herrera-Montalvo, Luis Alonso, Mendoza-Vargas, Alfredo, Reyes-Grajeda, Juan Pablo, Cruz-Cruz, Alonso D., Velázquez-Cruz, Rafael, Torres-Espíndola, Luz María, Sierra-Vargas, Martha Patricia, Camarena, Angel, Ruiz, Víctor, Chávez-Alderete, Jaime, Jaime-Capetillo, María Esther, Guadarrama-Pérez, Cristóbal, Zúñiga-Ramos, Joaquin, Olivera-Ramírez, Alejandra, Martínez, Miguel Angel López, Serna-Muñoz, Ricardo, Garmendia, Adriana, Namkoong, Ho, Okada, Yukinori, Imoto, Seiya, Katayama, Kazuhiko, Fukunaga, Koichi, Kitagawa, Yuko, Sato, Toshiro, Hasegawa, Naoki, Kumanogoh, Atsushi, Kimura, Akinori, Ai, Masumi, Tokunaga, Katsushi, Kanai, Takanori, Miyano, Satoru, Ogawa, Seishi, Edahiro, Ryuya, Sonehara, Kyuto, Shirai, Yuya, Ishii, Makoto, Kabata, Hiroki, Masaki, Katsunori, Kamata, Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Tanaka, Hiromu, Morita, Atsuho, Lee, Ho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Mikami, Yohei, Tomono, Kazunori, Kato, Kazuto, Matsuda, Fumihiko, Takahashi, Meiko, Hizawa, Nobuyuki, Takeda, Yoshito, Hirata, Haruhiko, Shiroyama, Takayuki, Miyawaki, Satoru, Suzuki, Ken, Maeda, Yuichi, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Takahashi, Kunihiko, Anzai, Tatsuhiko, Hasegawa, Takanori, Ito, Satoshi, Koike, Ryuji, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro, Nakajima, Jun, Nannya, Yasuhito, Omae, Yosuke, Takahashi, Kazuhisa, Harada, Norihiro, Hiki, Makoto, Takagi, Haruhi, Nakamura, Ai, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Ishiguro, Takashi, Takayanagi, Noboru, Isono, Taisuke, Takaku, Yotaro, Takano, Kenji, Anan, Ryusuke, Nakajima, Yukiko, Nakano, Yasushi, Nishio, Kazumi, Ueda, Soichiro, Hayashi, Reina, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Mitamura, Keiko, Saito, Fumitake, Ueda, Tetsuya, Azuma, Masanori, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Yoshiyama, Takashi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Watanabe, Kazuyoshi, Manabe, Tadashi, Ito, Fumimaro, Fukui, Takahiro, Funatsu, Yohei, Koh, Hidefumi, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Saito, Fukuki, Yoshiya, Kazuhisa, Yoshihara, Tomoyuki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Nishi, Koichi, Nishitsuji, Masaru, Tani, Maiko, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Ogura, Takashi, Kitamura, Hideya, Murohashi, Kota, Nakachi, Ichiro, Baba, Rie, Arai, Daisuke, Fuke, Satoshi, Saito, Hiroshi, Kuwahara, Naota, Fujiwara, Akiko, Okada, Takenori, Baba, Tomoya, Noda, Junya, Mashimo, Shuko, Yagi, Kazuma, Shiomi, Tetsuya, Hashiguchi, Mizuha, Odani, Toshio, Mochimaru, Takao, Oyamada, Yoshitaka, Mori, Nobuaki, Izumi, Namiki, Nagata, Kaoru, Taki, Reiko, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Gon, Yasuhiro, Fujitani, Shigeki, Tsuchida, Tomoya, Yoshida, Toru, Kagaya, Takashi, Kita, Toshiyuki, Sakagami, Satoru, Kimizuka, Yoshifumi, Kawana, Akihiko, Nakamura, Yoshihiko, Ishikura, Hiroyasu, Takata, Tohru, Kikuchi, Takahide, Taniyama, Daisuke, Nakamura, Morio, Kodama, Nobuhiro, Kaneyama, Yasunari, Maeda, Shunsuke, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Ito, Akihiro, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Hashimoto, Naozumi, Wakahara, Keiko, Ando, Akira, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Sageshima, Hisako, Nakada, Taka-Aki, Abe, Ryuzo, Shimada, Tadanaga, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Yamasaki, Masaki, Hashimoto, Satoru, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Takada, Minoru, Kanda, Hidenori, Komase, Yuko, Sano, Fumiaki, Asano, Koichiro, Oguma, Tsuyoshi, Harada, Masahiro, Takahashi, Takeshi, Shibusawa, Takayuki, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Izumo, Takehiro, Inomata, Minoru, Awano, Nobuyasu, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Kitagawa, Yuichiro, Yoshida, Shozo, Ogura, Shinji, Nishiyama, Kei, Yoshida, Kousuke, Beppu, Satoru, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Inoue, Yoshiaki, Yamagata, Kunihiro, Chiba, Shigeru, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Shibata, Yoko, Tanino, Yoshinori, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Imamura, Tomonori, Umeda, Akira, Shimada, Hisato, Endo, Mayu, Hayashi, Shinichi, Takahashi, Mai, Nakano, Shigefumi, Yatomi, Masakiyo, Maeno, Toshitaka, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Nishida, Nao, Kawai, Yosuke, Sugiyama, Masaya, Alawneh, Laith M., Maswadeh, Kinda B., Alsoub, Fatima S., AlRawashdeh, Tala J., Esawi, Ezaldeen, Abu Alragheb, Bayan O., Maswadeh, Ahmad B., Al-Kadash, Abdulfattah, Al-Ani, Abdallah, Alsafadi, Dana B., Shahin, Mohammad A., Qtaish, Nuseibah Al, Alawneh, Fade M., Abulail, Joseph A., Zhlawi, Hadi J., Alhousani, Tasneem N., Alzuraiqi, Mohammad R., Al-Ja’afreh, Mohammad M., Allouzy, Sara K., ALjalamdeh, Mothafer, Mansour, Tareq M., Alamer, Lina M., Issa, Ali Banni, Bani younis, Fatima M., Hawari, Feras I., Hayajneh, Wail A., Obeidat, Nathir M., Ahram, Mamoun, Zhlawi, Moh’d Wahib J., Alshaer, Walhan, Al-Kasasbeh, Malak M., Naffa, Randa G., Ismail, Mohammad A., Abdullah, Mohammed S., Ismail, Said I., Obeidat, Ma’en, Hernández Cordero, Ana I., Sin, Don D., Bossé, Yohan, Joubert, Philippe, Hao, Ke, Nickle, David, Timens, Wim, van den Berge, Maarten, Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Mandla, Ravi, Schroeder, Philip, Perez, Emma F., Lee, Seung Hyuk T., Flores-Silva, Fernando Daniel, Chiquete, Erwin, Cantú-Brito, Carlos, Sifuentes-Osornio, José, de León-Garduño, Alfredo Ponce, Román-Montes, Carla Marina, Chávez-Manzanera, Emma, Velasco, Donaji Gómez, Martagón-Rosado, Alexandro, Cruz-Bautista, Ivette, Gómez-Pérez, Francisco Javier, Díaz-Olavarrieta, Claudia, Valdés, Paloma Almeda, Muñóz-Hernández, Linda Liliana, Mehta, Roopa Pravin, Elías-López, Daniel, Tusié-Luna, Teresa, Pajukanta, Päivi, Sukhatme, Mihir G., Moreno-Macías, Hortensia, Ruth, Johnson, González-Behn-Eschenburg, Sebastián, García-Grimshaw, Miguel, Guillen-Pineda, Luz Elizabeth, de los Ángeles Vargas-Martínez, María, Rodríguez, Maribel, Rodríguez-Guillén, Rosario, Ordoñez, María Luisa, Rajme-López, Sandra, González-Lara, María Fernanda, Luna-Moreno, Dalia, de Jesús Suárez López, Jannet, Guillén-Quintero, Daniela Mariel, Vega, Juan, Duran-Coyote, Salvador, Guerra-García, María Teresa, Durán-Gómez, Michelle, Vigueras-Hernández, Alma, Ramírez-Jiménez, Marco Eduardo, Grajeda-González, Samara Lissete, Ramos-Galicia, Enrique Manuel, Ramírez-Carrillo, Martha Fernanda, Fernandez-Ruiz, Juan, Chirino-Pérez, Amanda, Romero-Molina, Ángel Omar, Zavaleta, David Alejandro Fuentes, Jaramillo, María Andrea Mac Donald, López, Katia Jarely Prieto, Incontri-Abraham, Diego, Rosado, Wendy Natalia, Catalán, María Alonso, Aguilar, Sonia Evelyn Vital, Zamudio, Ileana Paola Montero, Ruíz-Ruíz, Eduardo, de Jesús Carrera García, Kevin, Guerrero, Cristina Villarreal, Martínez, Ana Isabel Rodríguez, Moscoso-Sánchez, Rogelio, del Consuelo Rodríguez Mancilla, María, Villa, Antonio, Luna-Ramírez, Samuel Alejandro, Hernández-Hernández, Sergio, Frias, Erika, Campos, Alejandro, Morales-Sosa, Paola Alessandra, Toxqui-Merchant, Luis Enrique, García, Karla, Pasaniuc, Bogdan, Butte, Manish J., Geschwind, Daniel H., Aguilar-Salinas, Carlos A., Heidecker, Bettina, Kurth, Florian, Sander, Leif E., Skurk, Carsten, Landmesser, Ulf, Karadeniz, Zehra, Wang, Xiaomin, Poller, Wolfgang, Suwalski, Phillip, Ripke, Stephan, Braun, Alice, Kraft, Julia, Mayer, Alena, Lippert, Lena J., Helbig, Elisa T., Thibeault, Charlotte, Awasthi, Swapnil, Mbarek, Hamdi, Saad, Chadi, Al-Sarraj, Yaser, Badji, Radja Messai, Al-Muftah, Wadha, Thani, Asma Al, Afifi, Nahla, Sadiq, Fouzia, Khan, Mohammad I., Bhutta, Muhammad J., Khan, Hania, Khan, Madeeha, Ain, Quratul, Junaid, Ayesha, Khan, Ejaz A., Sypniewski, Mateusz, Lejman, Adrian, Zawadzki, Paweł, Sztromwasser, Paweł, Król, Zbigniew, Dobosz, Paula, Stojak, Joanna, Flores, Carlos, Carracedo, Ángel, Aguilar, Carlos, Arranz, María J., Baptista-Rosas, Raúl C., Bezerra, Joao F., Bezerra, Marcos A. C., Brugada, Ramón, Bustos, Matilde, Castano, Luis, Conde-Vicente, Rosa, Cordero-Lorenzana, M. Lourdes, De Martino-Rodríguez, Alba, Domínguez-Garrido, Elena, Fariñas, María Carmen, Gil-Fournier, Belén, Herrero, María José, Lattig, María Claudia, Martín-López, Caridad, Martín, Vicente, Martinez-Nieto, Oscar, Martinez-Lopez, Iciar, Mazzeu, Juliana F., Macías, Eleuterio Merayo, Cuerda, Victor Moreno, Silbiger, Vivian N., Oliveira, Silviene F., Parellada, Mara, Santos, Ney P. C., Pérez-Matute, Patricia, Perez, Patricia, Perucho, Teresa, Porras-Hurtado, Gloria L., Pujol, Aurora, Fernández-Rodríguez, Amanda, Jimenez-Sousa, María A., Rodríguez-Ruiz, Emilio, Rodriguez-Artalejo, Fernando, Rodriguez-Garcia, José A., Ruiz-Cabello, Francisco, Soria, José Manuel, Tamayo, Eduardo, Teper, Alejandro, Torres-Tobar, Lilian, Urioste, Miguel, Yáñez, Zuleima, Zarate, Ruth, Guillen-Navarro, Encarna, Ayuso, Carmen, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Lapunzina, Pablo, Cruz, Raquel, Diz-de Almeida, Silvia, Ceballos, Francisco C., Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Quintela, Inés, Pita, Guillermo, Gago-Domínguez, Manuela, Porras, Marta Sevilla, Tenorio-Castaño, Jair Antonio, Nevado, Julian, Aguado, Jose María, Aguilera-Albesa, Sergio, Almadana, Virginia, Almoguera, Berta, Alvarez, Nuria, Andreu-Bernabeu, Álvaro, Arango, Celso, Artiga, Maria-Jesus, Barreda-Sánchez, María, Belhassen-Garcia, Moncef, Boix-Palop, Lucía, Brion, María, Carbonell, Cristina, Castelao, Jose E., Cortes-Sanchez, Jose L., Corton, Marta, Darnaude, M. Teresa, del Campo-Pérez, Victor, de Bustamante, Aranzazu Diaz, Luchessi, Andre D., Eiros, Rocío, Sanabria, Gladys Mercedes Estigarribia, Fernández-Robelo, Uxía, Fernández-Villa, Tania, Gómez-Arrue, Javier, Álvarez, Beatriz González, de Quirós, Fernan Gonzalez Bernaldo, González-Peñas, Javier, Gutiérrez-Bautista, Juan F., Herrero-Gonzalez, Antonio, Borja, Anabel Liger, Lopez-Rodriguez, Rosario, Mancebo, Esther, Martinez-Resendez, Michel F., Martinez-Perez, Angel, Minguez, Pablo, Ortega-Paino, Eva, Paz-Artal, Estela, Pérez-Tomás, M. Elena, Pinsach-Abuin, Mel·lina, Pompa-Mera, Ericka N., León, Soraya Ramiro, Resino, Salvador, Fernandes, Marianne R., Ruiz-Hornillos, Javier, Ryan, Pablo, Souto, Juan Carlos, Tamayo-Velasco, Alvaro, Taracido-Fernandez, Juan Carlos, Valencia-Ramos, Juan, de Heredia, Miguel López, Pedersen, Ole B., Erikstrup, Christian, Ostrowski, Sisse R., Stefansson, Kari, Mikkelsen, Susan, Sørensen, Erik, Burgos, Celia, Andersen, Steffen, Brugdorf, Kristoffer, Hansen, Thomas F., Hjalgrim, Henrik, Jemec, Gregor B., Nyegaard, Mette, Werge, Thomas, Johansson, Pär I., Didriksen, Maria, Schwinn, Michael, Jacobsen, Rikke L., Hindhede, Lotte, Rostgaard, Klaus, Gudbjartsson, Daniel, Stefánsson, Hreinn, Þorsteinsdóttir, Unnur, Nielsen, Kaspar R., Bruun, Mie Topholm, Dinh, Khoa M., Larsen, Margit A. H., Sækmose, Susanne G., Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Tardif, Nicolas, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Heid, Iris M., Wagner, Ralf, Überla, Klaus, Winkler, Thomas W., Wiegrebe, Simon, Gorski, Mathias, Stark, Klaus J., Peterhoff, David, Einhauser, Sebastian, Niller, Hans-Helmut, Beileke, Stephanie, Johnson, Ruth, Freimer, Nelson, Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikolas, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Solomonson, Matthew, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Zhou, Wei, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicolas, Koelling, Nils, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlos, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler-Palacin, Pere, Colobran, Roger, Martin-Nalda, Andrea, Parra-Martínez, Alba, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas-Rodriguez, Elisa, Cal-Sabater, Paloma, Segura, Tomás, González-Villar, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, and Menéndez-Valladares, Paloma
Published: 2023

6. RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia

Author: Ministerio de Ciencia e Innovación (España), Launay, Nathalie, Ruiz, Montserrat, Planas-Serra, Laura, Verdura, Edgard, Rodríguez-Palmero, Agustí, Schlüter, Agatha, Goicoechea, Leire, Guilera, Cristina, Casas, Josefina, Campelo, Felix, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Boespflug-Tanguy, Odile, Vazquez Cancela, Maria, Gutiérrez-Solana, Luis González, Casasnovas, Carlos, Area-Gomez, Estela, Pujol, Aurora, Ministerio de Ciencia e Innovación (España), Launay, Nathalie, Ruiz, Montserrat, Planas-Serra, Laura, Verdura, Edgard, Rodríguez-Palmero, Agustí, Schlüter, Agatha, Goicoechea, Leire, Guilera, Cristina, Casas, Josefina, Campelo, Felix, Jouanguy, Emmanuelle, Casanova, Jean-Laurent, Boespflug-Tanguy, Odile, Vazquez Cancela, Maria, Gutiérrez-Solana, Luis González, Casasnovas, Carlos, Area-Gomez, Estela, and Pujol, Aurora
Abstract: The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1 loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development.
Published: 2023

7. Interleukin-23 receptor signaling impairs the stability and function of colonic regulatory T cells

Author: Jacobse, Justin, Brown, Rachel E., Li, Jing, Pilat, Jennifer M., Pham, Ly, Short, Sarah P., Peek, Christopher T., Rolong, Andrea, Washington, M. Kay, Martinez-Barricarte, Ruben, Byndloss, Mariana X., Shelton, Catherine, Markle, Janet G., Latour, Yvonne L., Allaman, Margaret M., Cassat, James E., Wilson, Keith T., Choksi, Yash A., Williams, Christopher S., Lau, Ken S., Flynn, Charles R., Casanova, Jean Laurent, Rings, Edmond H.H.M., Samsom, Janneke N., Goettel, Jeremy A., Jacobse, Justin, Brown, Rachel E., Li, Jing, Pilat, Jennifer M., Pham, Ly, Short, Sarah P., Peek, Christopher T., Rolong, Andrea, Washington, M. Kay, Martinez-Barricarte, Ruben, Byndloss, Mariana X., Shelton, Catherine, Markle, Janet G., Latour, Yvonne L., Allaman, Margaret M., Cassat, James E., Wilson, Keith T., Choksi, Yash A., Williams, Christopher S., Lau, Ken S., Flynn, Charles R., Casanova, Jean Laurent, Rings, Edmond H.H.M., Samsom, Janneke N., and Goettel, Jeremy A.
Abstract: The cytokine interleukin-23 (IL-23) is involved in the pathogenesis of inflammatory and autoimmune conditions including inflammatory bowel disease (IBD). IL23R is enriched in intestinal Tregs, yet whether IL-23 modulates intestinal Tregs remains unknown. Here, investigating IL-23R signaling in Tregs specifically, we show that colonic Tregs highly express Il23r compared with Tregs from other compartments and their frequency is reduced upon IL-23 administration and impairs Treg suppressive function. Similarly, colonic Treg frequency is increased in mice lacking Il23r specifically in Tregs and exhibits a competitive advantage over IL-23R-sufficient Tregs during inflammation. Finally, IL-23 antagonizes liver X receptor pathway, cellular cholesterol transporter Abca1, and increases Treg apoptosis. Our results show that IL-23R signaling regulates intestinal Tregs by increasing cell turnover, antagonizing suppression, and decreasing cholesterol efflux. These results suggest that IL-23 negatively regulates Tregs in the intestine with potential implications for promoting chronic inflammation in patients with IBD.
Published: 2023

8. Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Author: Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Cabildo de Tenerife, Fundació La Marató de TV3, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Consejo Superior de Investigaciones Científicas (España), European Commission, Pérez-Tur, Jordi [0000-0002-9111-1712], Lee, Danyel, Le Pen, Jeremie, Yatim, Ahmad, Dong, Beihua, Aquino, Yann, Ogishi, Masato, Pescarmona, Remi, Talouarn, Estelle, Rinchai, Darawan, Zhang, Peng, Perret, Magali, Rice, Charles M., Silverman, Robert H., Zhang, Shen-Ying, Casanova, Jean-Laurent, Liu, Zhiyong, Jordan, Iolanda, Bozdemir, Sefika Elmas, Bayhan, Gulsum Iclal, Beaufils, Camille, Bizien, Lucy, Bisiaux, Aurelie, Lei, Weite, Hasan, Milena, Chen, Jie, Gaughan, Christina, Asthana, Abhishek, Libri, Valentina, Luna, Joseph M., Jaffre, Fabrice, Hoffmann, H-Heinrich, Michailidis, Eleftherios, Moreews, Marion, Seeleuthner, Yoann, Bilguvar, Kaya, Mane, Shrikant, Flores, Carlos, Zhang, Yu, Arias, Andres A., Bailey, Rasheed, Schluter, Agatha, Milisavljevic, Baptiste, Bigio, Benedetta, Le Voyer, Tom, Materna, Marie, Gervais, Adrian, Moncada-Velez, Marcela, Pala, Francesca, Lazarov, Tomi, Levy, Romain, Neehus, Anna-Lena, Rosain, Jeremie, Peel, Jessica, Chan, Yi-Hao, Morin, Marie-Paule, Pino-Ramírez, Rosa María, Belkaya, Serkan, Lorenzo, Lazaro, Anton, Jordi, Delafontaine, Selket, Toubiana, Julie, Bajolle, Fanny, Fumado, Victoria, DeDiego, Marta L., Fidouh, Nadhira, Rozenberg, Flore, Pérez-Tur, Jordi, Chen, Shuibing, Evans, Todd, Geissmann, Frederic, Lebon, Pierre, Weiss, Susan R., Bonnet, Damien, Duval, Xavier, Pan-Hammarström, Qiang, Planas, Anna M., Meyts, Isabelle, Haerynck, Filomeen, Pujol, Aurora, Sancho-Shimizu, Vanessa, Dalgard, Clifford L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Boisson, Bertrand, Maniatis, Tom, Zhang, Qian, Bastard, Paul, Notarangelo, Luigi, Beziat, Vivien, Pérez de Diego, Rebeca, Rodriguez-Gallego, Carlos, Su, Helen C., Lifton, Richard P, Jouanguy, Emmanuelle, Cobat, Aurelie, Alsina, Laia, Keles, Sevgi, Haddad, Elie, Abel, Laurent, Belot, Alexandre, Quintana-Murci, Lluis, Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Cabildo de Tenerife, Fundació La Marató de TV3, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Consejo Superior de Investigaciones Científicas (España), European Commission, Pérez-Tur, Jordi [0000-0002-9111-1712], Lee, Danyel, Le Pen, Jeremie, Yatim, Ahmad, Dong, Beihua, Aquino, Yann, Ogishi, Masato, Pescarmona, Remi, Talouarn, Estelle, Rinchai, Darawan, Zhang, Peng, Perret, Magali, Rice, Charles M., Silverman, Robert H., Zhang, Shen-Ying, Casanova, Jean-Laurent, Liu, Zhiyong, Jordan, Iolanda, Bozdemir, Sefika Elmas, Bayhan, Gulsum Iclal, Beaufils, Camille, Bizien, Lucy, Bisiaux, Aurelie, Lei, Weite, Hasan, Milena, Chen, Jie, Gaughan, Christina, Asthana, Abhishek, Libri, Valentina, Luna, Joseph M., Jaffre, Fabrice, Hoffmann, H-Heinrich, Michailidis, Eleftherios, Moreews, Marion, Seeleuthner, Yoann, Bilguvar, Kaya, Mane, Shrikant, Flores, Carlos, Zhang, Yu, Arias, Andres A., Bailey, Rasheed, Schluter, Agatha, Milisavljevic, Baptiste, Bigio, Benedetta, Le Voyer, Tom, Materna, Marie, Gervais, Adrian, Moncada-Velez, Marcela, Pala, Francesca, Lazarov, Tomi, Levy, Romain, Neehus, Anna-Lena, Rosain, Jeremie, Peel, Jessica, Chan, Yi-Hao, Morin, Marie-Paule, Pino-Ramírez, Rosa María, Belkaya, Serkan, Lorenzo, Lazaro, Anton, Jordi, Delafontaine, Selket, Toubiana, Julie, Bajolle, Fanny, Fumado, Victoria, DeDiego, Marta L., Fidouh, Nadhira, Rozenberg, Flore, Pérez-Tur, Jordi, Chen, Shuibing, Evans, Todd, Geissmann, Frederic, Lebon, Pierre, Weiss, Susan R., Bonnet, Damien, Duval, Xavier, Pan-Hammarström, Qiang, Planas, Anna M., Meyts, Isabelle, Haerynck, Filomeen, Pujol, Aurora, Sancho-Shimizu, Vanessa, Dalgard, Clifford L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Boisson, Bertrand, Maniatis, Tom, Zhang, Qian, Bastard, Paul, Notarangelo, Luigi, Beziat, Vivien, Pérez de Diego, Rebeca, Rodriguez-Gallego, Carlos, Su, Helen C., Lifton, Richard P, Jouanguy, Emmanuelle, Cobat, Aurelie, Alsina, Laia, Keles, Sevgi, Haddad, Elie, Abel, Laurent, Belot, Alexandre, and Quintana-Murci, Lluis
Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C
Published: 2023

9. Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy

Author: Experimental Cardiology Laboratory, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Zhang, Yujiao, Vandestienne, Marie, Lavillegrand, Jean Rémi, Joffre, Jeremie, Santos-Zas, Icia, Lavelle, Aonghus, Zhong, Xiaodan, Le Goff, Wilfried, Guérin, Maryse, Al-Rifai, Rida, Laurans, Ludivine, Bruneval, Patrick, Guérin, Coralie, Diedisheim, Marc, Migaud, Melanie, Puel, Anne, Lanternier, Fanny, Casanova, Jean Laurent, Cochain, Clément, Zernecke, Alma, Saliba, Antoine Emmanuel, Mokry, Michal, Silvestre, Jean Sebastien, Tedgui, Alain, Mallat, Ziad, Taleb, Soraya, Lenoir, Olivia, Vindis, Cécile, Camus, Stéphane M., Sokol, Harry, Ait-Oufella, Hafid, Experimental Cardiology Laboratory, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Zhang, Yujiao, Vandestienne, Marie, Lavillegrand, Jean Rémi, Joffre, Jeremie, Santos-Zas, Icia, Lavelle, Aonghus, Zhong, Xiaodan, Le Goff, Wilfried, Guérin, Maryse, Al-Rifai, Rida, Laurans, Ludivine, Bruneval, Patrick, Guérin, Coralie, Diedisheim, Marc, Migaud, Melanie, Puel, Anne, Lanternier, Fanny, Casanova, Jean Laurent, Cochain, Clément, Zernecke, Alma, Saliba, Antoine Emmanuel, Mokry, Michal, Silvestre, Jean Sebastien, Tedgui, Alain, Mallat, Ziad, Taleb, Soraya, Lenoir, Olivia, Vindis, Cécile, Camus, Stéphane M., Sokol, Harry, and Ait-Oufella, Hafid
Published: 2023

10. Human genetic determinants of COVID-19 in Brazil: challenges and future plans

Author: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Instituto Nacional de Genética Médica Populacional (Brasil), Hospital de Clínicas de Porto Alegre, Fundo de Incentivo à Pesquisa e Eventos (Brasil), Fam, Bibiana S de Oliveira, Feira, Marilea Furtado, Cadore, Nathan Araujo, Sbruzzi, Renan, Hünemeier, Tábita, Abel, Laurent, Zhang, Qian, Casanova, Jean-Laurent, Vianna, Fernanda Sales Luiz, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Instituto Nacional de Genética Médica Populacional (Brasil), Hospital de Clínicas de Porto Alegre, Fundo de Incentivo à Pesquisa e Eventos (Brasil), Fam, Bibiana S de Oliveira, Feira, Marilea Furtado, Cadore, Nathan Araujo, Sbruzzi, Renan, Hünemeier, Tábita, Abel, Laurent, Zhang, Qian, Casanova, Jean-Laurent, and Vianna, Fernanda Sales Luiz
Abstract: COVID-19 pandemic represented a worldwide major challenge in different areas, and efforts undertaken by the scientific community led to the understanding of some of the genetic determinants that influence the different COVID-19 outcomes. In this paper, we review the studies about the role of human genetics in COVID-19 severity and how Brazilian studies also contributed to those findings. Rare variants in genes related to Inborn Errors of Immunity (IEI) in the type I interferons pathway, and its phenocopies, have been described as being causative of severe outcomes. IEI and its phenocopies are present in Brazil, not only in COVID-19 patients, but also in autoimmune conditions and severe reactions to yellow fever vaccine. In addition, studies focusing on common variants and GWAS studies encompassing worldwide patients have found several loci associated with COVID-19 severity. A GWAS study including only Brazilian COVID-19 patients identified a new locus 1q32.1 associated with COVID-19 severity. Thus, more comprehensive studies considering the Brazilian genomic diversity should be performed, since they can help to reveal not only what are the genetic determinants that contribute to the different outcomes for COVID-19 in the Brazilian population, but in the understanding of human genetics in different health conditions.
Published: 2023

11. A progeroid syndrome caused by a deep intronic variant in TAPT1 is revealed by RNA/SI-NET sequencing

Author: Reversade, Bruno; Altunoğlu, Umut (ORCID 0000-0002-3172-5368 & YÖK ID 126174); Sarıbaş, Burak; Nabavizadeh, Nasrinsadat; Escande-Beillard, Nathalie (ORCID 0000-0002-7706-1608 & YÖK ID 396501), Bressin, Annkatrin; Shboul, Mohammad; Moreno Traspas, Ricardo; Chia, Poh Hui; Bonnard, Carine; Szenker-Ravi, Emmanuelle; Beillard, Emmanuel; Hojati, Zohreh; Drutman, Scott; Freier, Susanne; El-Khateeb, Mohammad; Fathallah, Rajaa; Casanova, Jean-Laurent; Soror, Wesam; Arafat, Alaa; Mayer, Andreas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine; Graduate School of Health Sciences, Reversade, Bruno; Altunoğlu, Umut (ORCID 0000-0002-3172-5368 & YÖK ID 126174); Sarıbaş, Burak; Nabavizadeh, Nasrinsadat; Escande-Beillard, Nathalie (ORCID 0000-0002-7706-1608 & YÖK ID 396501), Bressin, Annkatrin; Shboul, Mohammad; Moreno Traspas, Ricardo; Chia, Poh Hui; Bonnard, Carine; Szenker-Ravi, Emmanuelle; Beillard, Emmanuel; Hojati, Zohreh; Drutman, Scott; Freier, Susanne; El-Khateeb, Mohammad; Fathallah, Rajaa; Casanova, Jean-Laurent; Soror, Wesam; Arafat, Alaa; Mayer, Andreas, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine; Graduate School of Health Sciences
Abstract: Exome sequencing has introduced a paradigm shift for the identification of germline variations responsible for Mendelian diseases. However, non-coding regions, which make up 98% of the genome, cannot be captured. The lack of functional annotation for intronic and intergenic variants makes RNA-seq a powerful companion diagnostic. Here, we illustrate this point by identifying six patients with a recessive Osteogenesis Imperfecta (OI) and neonatal progeria syndrome. By integrating homozygosity mapping and RNA-seq, we delineated a deep intronic TAPT1 mutation (c.1237-52 G>A) that segregated with the disease. Using SI-NET-seq, we document that TAPT1's nascent transcription was not affected in patients' fibroblasts, indicating instead that this variant leads to an alteration of pre-mRNA processing. Predicted to serve as an alternative splicing branchpoint, this mutation enhances TAPT1 exon 12 skipping, creating a protein-null allele. Additionally, our study reveals dysregulation of pathways involved in collagen and extracellular matrix biology in disease-relevant cells. Overall, our work highlights the power of transcriptomic approaches in deciphering the repercussions of non-coding variants, as well as in illuminating the molecular mechanisms of human diseases., Deutsche Forschungsgemeinschaft (DFG); Scientific and Technological Research Council of Turkey (TÜBİTAK); TÜBİTAK 2232 International Fellowship for Outstanding Researchers Program; Branco Weiss Foundation; EMBO Young Investigator; Strategic Positioning Fund on Genetic Orphan Diseases (GODAFIT); Use-Inspired Basic Research (UIBR) Grant; Agency for Science, Technology and Research (A*STAR); Max Planck Society
Published: 2023

12. Immigration in science.

Author: Casanova, Jean-Laurent, Casanova, Jean-Laurent, Holtzman, David M, Kaech, Susan M, Lanier, Lewis L, Nathan, Carl F, Rudensky, Alexander Y, Tuveson, David, Wolchok, Jedd D, Casanova, Jean-Laurent, Casanova, Jean-Laurent, Holtzman, David M, Kaech, Susan M, Lanier, Lewis L, Nathan, Carl F, Rudensky, Alexander Y, Tuveson, David, and Wolchok, Jedd D
Abstract: The advance of science is dependent upon collaboration, which does not have a visa attached to it. Indeed, over 40% of all American-based Nobel Prize winners are immigrants, and data from the National Science Foundation show that 49% of postdocs and 29% of science and engineering faculty in the US are foreign-born. However, restrictive new immigration policies in the US have left many scientists deeply concerned about their future and many American-based laboratories worried about attracting the best talent. At JEM, we're celebrating immigration by sharing the experiences of immigrant and nonimmigrant scientists on our editorial board. Alexander Rudensky and Jean-Laurent Casanova give their firsthand perspective on immigrating to the US, while Jedd Wolchok, Carl Nathan, David Holtzman, Susan Kaech, Lewis Lanier, and David Tuveson reflect on how immigration has affected their laboratories.
Published: 2020

13. Immigration in science.

Author: Casanova, Jean-Laurent, Casanova, Jean-Laurent, Holtzman, David M, Kaech, Susan M, Lanier, Lewis L, Nathan, Carl F, Rudensky, Alexander Y, Tuveson, David, Wolchok, Jedd D, Casanova, Jean-Laurent, Casanova, Jean-Laurent, Holtzman, David M, Kaech, Susan M, Lanier, Lewis L, Nathan, Carl F, Rudensky, Alexander Y, Tuveson, David, and Wolchok, Jedd D
Abstract: The advance of science is dependent upon collaboration, which does not have a visa attached to it. Indeed, over 40% of all American-based Nobel Prize winners are immigrants, and data from the National Science Foundation show that 49% of postdocs and 29% of science and engineering faculty in the US are foreign-born. However, restrictive new immigration policies in the US have left many scientists deeply concerned about their future and many American-based laboratories worried about attracting the best talent. At JEM, we're celebrating immigration by sharing the experiences of immigrant and nonimmigrant scientists on our editorial board. Alexander Rudensky and Jean-Laurent Casanova give their firsthand perspective on immigrating to the US, while Jedd Wolchok, Carl Nathan, David Holtzman, Susan Kaech, Lewis Lanier, and David Tuveson reflect on how immigration has affected their laboratories.
Published: 2020

14. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Author: MMB Medische Staf, Infection & Immunity, MMB, Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C, Kaja, Elżbieta, Drolet, Beth A, Zhang, Qian, O'Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C, Casanova, Jean-Laurent, Spaan, András N, MMB Medische Staf, Infection & Immunity, MMB, Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C, Kaja, Elżbieta, Drolet, Beth A, Zhang, Qian, O'Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C, Casanova, Jean-Laurent, and Spaan, András N
Published: 2022

15. Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Author: Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
Published: 2022
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16. Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Author: Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
Published: 2022
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17. Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Author: Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
Published: 2022
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18. X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

Author: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, and Pan-Hammarstrom, Qiang
Abstract: Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
Published: 2022
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19. X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

Author: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, and Pan-Hammarstrom, Qiang
Abstract: Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
Published: 2022
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20. X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

Author: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, and Pan-Hammarstrom, Qiang
Abstract: Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
Published: 2022
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21. Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Author: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Zhang, Qian, Matuozzo, Daniela, Le Pen, Jérémie, Lee, Danyel, Moens, Leen, Asano, Takaki, Bohlen, Jonathan, Liu, Zhiyong, Moncada-Velez, Marcela, Kendir-Demirkol, Yasemin, Jing, Huie, Bizien, Lucy, Marchal, Astrid, Abolhassani, Hassan, Delafontaine, Selket, Bucciol, Giorgia, COVID Human Genetic Effort, Bayhan, Gulsum Ical, Keles, Sevgi, Kiykim, Ayca, Hancerli, Selda, Haerynck, Filomeen, Florkin, Benoit, Hatipoglu, Nevin, Ozcelik, Tayfun, Morelle, Guillaume, Zatz, Mayana, Ng, Lisa F P, Lye, David Chien, Young, Barnaby Edward, Leo, Yee-Sin, Dalgard, Clifton L, Lifton, Richard P, Renia, Laurent, Meyts, Isabelle, Jouanguy, Emmanuelle, Hammarström, Lennart, Pan-Hammarström, Qiang, Boisson, Bertrand, Bastard, Paul, Su, Helen C, Boisson-Dupuis, Stéphanie, Abel, Laurent, Rice, Charles M, Zhang, Shen-Ying, Cobat, Aurélie, Casanova, Jean-Laurent, Froidure, Antoine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Zhang, Qian, Matuozzo, Daniela, Le Pen, Jérémie, Lee, Danyel, Moens, Leen, Asano, Takaki, Bohlen, Jonathan, Liu, Zhiyong, Moncada-Velez, Marcela, Kendir-Demirkol, Yasemin, Jing, Huie, Bizien, Lucy, Marchal, Astrid, Abolhassani, Hassan, Delafontaine, Selket, Bucciol, Giorgia, COVID Human Genetic Effort, Bayhan, Gulsum Ical, Keles, Sevgi, Kiykim, Ayca, Hancerli, Selda, Haerynck, Filomeen, Florkin, Benoit, Hatipoglu, Nevin, Ozcelik, Tayfun, Morelle, Guillaume, Zatz, Mayana, Ng, Lisa F P, Lye, David Chien, Young, Barnaby Edward, Leo, Yee-Sin, Dalgard, Clifton L, Lifton, Richard P, Renia, Laurent, Meyts, Isabelle, Jouanguy, Emmanuelle, Hammarström, Lennart, Pan-Hammarström, Qiang, Boisson, Bertrand, Bastard, Paul, Su, Helen C, Boisson-Dupuis, Stéphanie, Abel, Laurent, Rice, Charles M, Zhang, Shen-Ying, Cobat, Aurélie, Casanova, Jean-Laurent, and Froidure, Antoine
Abstract: Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.
Published: 2022

22. Studying severe long COVID to understand post-infectious disorders beyond COVID-19.

Author: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de pneumologie, Brodin, Petter, Casari, Giorgio, Townsend, Liam, O'Farrelly, Cliona, Tancevski, Ivan, Löffler-Ragg, Judith, Mogensen, Trine H, Casanova, Jean Laurent, COVID Human Genetic Effort, Froidure, Antoine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de pneumologie, Brodin, Petter, Casari, Giorgio, Townsend, Liam, O'Farrelly, Cliona, Tancevski, Ivan, Löffler-Ragg, Judith, Mogensen, Trine H, Casanova, Jean Laurent, COVID Human Genetic Effort, and Froidure, Antoine
Published: 2022

23. Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

Author: Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Published: 2022
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24. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Author: Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., DeRisi, Joseph L., Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., and DeRisi, Joseph L.
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022
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25. Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Author: Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
Published: 2022
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26. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Author: Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., DeRisi, Joseph L., Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., and DeRisi, Joseph L.
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022
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27. Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

Author: Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Published: 2022
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28. Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

Author: Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Published: 2022
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29. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Author: Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., DeRisi, Joseph L., Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., and DeRisi, Joseph L.
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022
Full Text: View/download PDF

30. Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

Author: Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Published: 2022
Full Text: View/download PDF

31. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Author: Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., DeRisi, Joseph L., Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., and DeRisi, Joseph L.
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022
Full Text: View/download PDF

32. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Author: Vazquez, Sara E, Vazquez, Sara E, Mann, Sabrina A, Bodansky, Aaron, Kung, Andrew F, Quandt, Zoe, Ferré, Elise MN, Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y, Tagi, Veronica M, Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R, Kämpe, Olle, Dobbs, Kerry, Delmonte, Ottavia M, Bacchetta, Rosa, Notarangelo, Luigi D, Burns, Jane C, Casanova, Jean-Laurent, Lionakis, Michail S, Torgerson, Troy R, Anderson, Mark S, DeRisi, Joseph L, Vazquez, Sara E, Vazquez, Sara E, Mann, Sabrina A, Bodansky, Aaron, Kung, Andrew F, Quandt, Zoe, Ferré, Elise MN, Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y, Tagi, Veronica M, Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R, Kämpe, Olle, Dobbs, Kerry, Delmonte, Ottavia M, Bacchetta, Rosa, Notarangelo, Luigi D, Burns, Jane C, Casanova, Jean-Laurent, Lionakis, Michail S, Torgerson, Troy R, Anderson, Mark S, and DeRisi, Joseph L
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022

33. X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

Author: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, and Pan-Hammarstrom, Qiang
Abstract: Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
Published: 2022
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34. Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Author: Ogishi, Masato, Augusto Arias, Andres, Yang, Rui, Han, Ji Eun, Zhang, Peng, Rinchai, Darawan, Halpern, Joshua, Mulwa, Jeanette, Keating, Narelle, Chrabieh, Maya, Laine, Candice, Seeleuthner, Yoann, Ramirez-Alejo, Noe, Nekooie-Marnany, Nioosha, Guennoun, Andrea, Muller-Fleckenstein, Ingrid, Fleckenstein, Bernhard, Kilic, Sara S., Minegishi, Yoshiyuki, Ehl, Stephan, Kaiser-Labusch, Petra, Kendir-Demirkol, Yasemin, Rozenberg, Flore, Errami, Abderrahmane, Zhang, Shen-Ying, Zhang, Qian, Bohlen, Jonathan, Puel, Anne, Jouanguy, Emmanuelle, Pourmoghaddas, Zahra, Bakhtiar, Shahrzad, Willasch, Andre M., Horneff, Gerd, Llanora, Genevieve, Shek, Lynette P., Chai, Louis Y. A., Tay, Sen Hee, Rahimi, Hamid H., Mahdaviani, Seyed Alireza, Nepesov, Serdar, Bousfiha, Aziz A., Erdeniz, Emine Hafize, Karbuz, Adem, Marr, Nico, Navarrete, Carmen, Adeli, Mehdi, Hammarstrom, Lennart, Abolhassani, Hassan, Parvaneh, Nima, Al Muhsen, Saleh, Alosaimi, Mohammed F., Alsohime, Fahad, Nourizadeh, Maryam, Moin, Mostafa, Arnaout, Rand, Alshareef, Saad, El-Baghdadi, Jamila, Genel, Ferah, Sherkat, Roya, Kiykim, Ayca, Yucel, Esra, Keles, Sevgi, Bustamante, Jacinta, Abel, Laurent, Casanova, Jean-Laurent, Boisson-Dupuis, Stephanie, Ogishi, Masato, Augusto Arias, Andres, Yang, Rui, Han, Ji Eun, Zhang, Peng, Rinchai, Darawan, Halpern, Joshua, Mulwa, Jeanette, Keating, Narelle, Chrabieh, Maya, Laine, Candice, Seeleuthner, Yoann, Ramirez-Alejo, Noe, Nekooie-Marnany, Nioosha, Guennoun, Andrea, Muller-Fleckenstein, Ingrid, Fleckenstein, Bernhard, Kilic, Sara S., Minegishi, Yoshiyuki, Ehl, Stephan, Kaiser-Labusch, Petra, Kendir-Demirkol, Yasemin, Rozenberg, Flore, Errami, Abderrahmane, Zhang, Shen-Ying, Zhang, Qian, Bohlen, Jonathan, Puel, Anne, Jouanguy, Emmanuelle, Pourmoghaddas, Zahra, Bakhtiar, Shahrzad, Willasch, Andre M., Horneff, Gerd, Llanora, Genevieve, Shek, Lynette P., Chai, Louis Y. A., Tay, Sen Hee, Rahimi, Hamid H., Mahdaviani, Seyed Alireza, Nepesov, Serdar, Bousfiha, Aziz A., Erdeniz, Emine Hafize, Karbuz, Adem, Marr, Nico, Navarrete, Carmen, Adeli, Mehdi, Hammarstrom, Lennart, Abolhassani, Hassan, Parvaneh, Nima, Al Muhsen, Saleh, Alosaimi, Mohammed F., Alsohime, Fahad, Nourizadeh, Maryam, Moin, Mostafa, Arnaout, Rand, Alshareef, Saad, El-Baghdadi, Jamila, Genel, Ferah, Sherkat, Roya, Kiykim, Ayca, Yucel, Esra, Keles, Sevgi, Bustamante, Jacinta, Abel, Laurent, Casanova, Jean-Laurent, and Boisson-Dupuis, Stephanie
Abstract: Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-gamma is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Published: 2022

35. Decoding the Human Genetic and Immunological Basis of COVID-19 mRNA Vaccine-Induced Myocarditis

Author: Bolze, Alexandre, Mogensen, Trine, Zhang, Shen-Ying, Abel, Laurent, Andreakos, Evangelos, Arkin, Lisa M., Borghesi, Alessandro, Brodin, Peter, Hagin, David, Novelli, Giuseppe, Okada, Satoshi, Peter, Jonny, Renia, Laurent, Severe, Karine, Tiberghien, Pierre, Vinh, Donald C., Cirulli, Elizabeth T., Casanova, Jean-Laurent, Pérez-Tur, Jordi, Planas, Anna M., Hsieh, Elena W. Y., Bolze, Alexandre, Mogensen, Trine, Zhang, Shen-Ying, Abel, Laurent, Andreakos, Evangelos, Arkin, Lisa M., Borghesi, Alessandro, Brodin, Peter, Hagin, David, Novelli, Giuseppe, Okada, Satoshi, Peter, Jonny, Renia, Laurent, Severe, Karine, Tiberghien, Pierre, Vinh, Donald C., Cirulli, Elizabeth T., Casanova, Jean-Laurent, Pérez-Tur, Jordi, Planas, Anna M., and Hsieh, Elena W. Y.
Abstract: More than 10 billion doses of COVID-19 vaccines have been administered worldwide in the span of 18 months, providing an unprecedented opportunity to study and understand immunological responses and clinical reactions to vaccines. While severe adverse reactions to live-attenuated viral or bacterial vaccines have been successfully deciphered since the 1950s, with the discovery of a wide range of underlying inborn errors of immunity [1, 2], there is currently no molecular, cellular, and immunological explanation for life-threatening reactions to any other type of vaccine. COVID-19 mRNA vaccines are very effective at preventing hypoxemic COVID-19 pneumonia. For example, their efficacy for preventing invasive mechanical ventilation and in-hospital death has been estimated at 90% (95% CI = 88–91%) [3]. COVID-19 mRNA vaccines are also well tolerated by most people, with either no side effects or mild local/systemic reactions, such as pain at the injection site, fever, or chills in the days following vaccination [4]. However, rare but serious adverse events have been observed, including anaphylaxis, myocarditis, Guillain-Barré syndrome, transverse myelitis, Bell’s palsy, and multisystem inflammatory syndrome [4,5,6,7]. These adverse events have a combined prevalence of about 90 per million doses administered [4]. It is unknown whether they are triggered by the adjuvant (lipid nanoparticles for the mRNA vaccines), the vaccine antigen (the perfusion-stabilized spike protein translated by the human cells), the core components of the vaccine (the nucleoside-modified mRNA), or a combination thereof. Some possible mechanisms have been suggested [8,9,10], but the underlying immunopathology and, hence, the risk factors predisposing a minority of vaccinees to experience any of these severe reactions remain unknown.
Published: 2022

36. The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments:Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021

Author: Tur, Carmen, Dubessy, Anne Laure, Otero-Romero, Susana, Amato, Maria Pia, Derfuss, Tobias, Di Pauli, Franziska, Iacobaeus, Ellen, Mycko, Marcin, Abboud, Hesham, Achiron, Anat, Bellinvia, Angelo, Boyko, Alexey, Casanova, Jean Laurent, Clifford, David, Dobson, Ruth, Farez, Mauricio F., Filippi, Massimo, Fitzgerald, Kathryn C., Fonderico, Mattia, Gouider, Riadh, Hacohen, Yael, Hellwig, Kerstin, Hemmer, Bernhard, Kappos, Ludwig, Ladeira, Filipa, Lebrun-Frénay, Christine, Louapre, Céline, Magyari, Melinda, Mehling, Matthias, Oreja-Guevara, Celia, Pandit, Lekha, Papeix, Caroline, Piehl, Fredrik, Portaccio, Emilio, Ruiz-Camps, Isabel, Selmaj, Krzysztof, Simpson-Yap, Steve, Siva, Aksel, Sorensen, Per Soelberg, Sormani, Maria Pia, Trojano, Maria, Vaknin-Dembinsky, Adi, Vukusic, Sandra, Weinshenker, Brian, Wiendl, Heinz, Winkelmann, Alexander, Zuluaga Rodas, María Isabel, Tintoré, Mar, Stankoff, Bruno, Tur, Carmen, Dubessy, Anne Laure, Otero-Romero, Susana, Amato, Maria Pia, Derfuss, Tobias, Di Pauli, Franziska, Iacobaeus, Ellen, Mycko, Marcin, Abboud, Hesham, Achiron, Anat, Bellinvia, Angelo, Boyko, Alexey, Casanova, Jean Laurent, Clifford, David, Dobson, Ruth, Farez, Mauricio F., Filippi, Massimo, Fitzgerald, Kathryn C., Fonderico, Mattia, Gouider, Riadh, Hacohen, Yael, Hellwig, Kerstin, Hemmer, Bernhard, Kappos, Ludwig, Ladeira, Filipa, Lebrun-Frénay, Christine, Louapre, Céline, Magyari, Melinda, Mehling, Matthias, Oreja-Guevara, Celia, Pandit, Lekha, Papeix, Caroline, Piehl, Fredrik, Portaccio, Emilio, Ruiz-Camps, Isabel, Selmaj, Krzysztof, Simpson-Yap, Steve, Siva, Aksel, Sorensen, Per Soelberg, Sormani, Maria Pia, Trojano, Maria, Vaknin-Dembinsky, Adi, Vukusic, Sandra, Weinshenker, Brian, Wiendl, Heinz, Winkelmann, Alexander, Zuluaga Rodas, María Isabel, Tintoré, Mar, and Stankoff, Bruno
Abstract: Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
Published: 2022

37. Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19

Author: Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Delavari, Samaneh, Landegren, Nils, Shokri, Sima, Bastard, Paul, Du, Likun, Zuo, Fanglei, Hajebi, Reza, Abolnezhadian, Farhad, Iranparast, Sara, Modaresi, Mohammadreza, Vosughimotlagh, Ahmad, Salami, Fereshte, Aranda-Guillen, Maribel, Cobat, Aurelie, Marcotte, Harold, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Casanova, Jean-Laurent, Kämpe, Olle, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. Objective: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. Methods: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. Results: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. Conclusions: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Published: 2022
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38. Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq

Author: Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., DeRisi, Joseph L., Vazquez, Sara E., Mann, Sabrina A., Bodansky, Aaron, Kung, Andrew F., Quandt, Zoe, Ferre, Elise M. N., Landegren, Nils, Eriksson, Daniel, Bastard, Paul, Zhang, Shen-Ying, Liu, Jamin, Mitchell, Anthea, Proekt, Irina, Yu, David, Mandel-Brehm, Caleigh, Wang, Chung-Yu, Miao, Brenda, Sowa, Gavin, Zorn, Kelsey, Chan, Alice Y., Tagi, Veronica M., Shimizu, Chisato, Tremoulet, Adriana, Lynch, Kara, Wilson, Michael R., Kaempe, Olle, Dobbs, Kerry, Delmonte, Ottavia M., Bacchetta, Rosa, Notarangelo, Luigi D., Burns, Jane C., Casanova, Jean-Laurent, Lionakis, Michail S., Torgerson, Troy R., Anderson, Mark S., and DeRisi, Joseph L.
Abstract: Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
Published: 2022
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39. Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome

Author: Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Landegren, Nils, Bastard, Paul, Materna, Marie, Modaresi, Mohammadreza, Du, Likun, Aranda-Guillen, Maribel, Sardh, Fabian, Zuo, Fanglei, Zhang, Peng, Marcotte, Harold, Marr, Nico, Khan, Taushif, Ata, Manar, Al-Ali, Fatima, Pescarmona, Remi, Belot, Alexandre, Beziat, Vivien, Zhang, Qian, Casanova, Jean-Laurent, Kämpe, Olle, Zhang, Shen-Ying, Hammarström, Lennart, and Pan-Hammarström, Qiang
Abstract: Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
Published: 2022
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40. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection

Author: National Institutes of Health (US), National Center for Advancing Translational Sciences (US), National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, Université de Paris, European Commission, Hellenic Foundation for Research and Innovation, Science Foundation Ireland, Regione Lazio, Generalitat de Catalunya, National Institute of Allergy and Infectious Diseases (US), Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C., Kaja, Elżbieta, Drolet, Beth A., Zhang, Qian, O’Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C., Casanova, Jean-Laurent, Spaan, András N., National Institutes of Health (US), National Center for Advancing Translational Sciences (US), National Human Genome Research Institute (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, Université de Paris, European Commission, Hellenic Foundation for Research and Innovation, Science Foundation Ireland, Regione Lazio, Generalitat de Catalunya, National Institute of Allergy and Infectious Diseases (US), Andreakos, Evangelos, Abel, Laurent, Vinh, Donald C., Kaja, Elżbieta, Drolet, Beth A., Zhang, Qian, O’Farrelly, Cliona, Novelli, Giuseppe, Rodríguez-Gallego, Carlos, Haerynck, Filomeen, Prando, Carolina, Pujol, Aurora, COVID Human Genetic Effort, Su, Helen C., Casanova, Jean-Laurent, and Spaan, András N.
Abstract: SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological determinants of resistance to infection per se remain unknown. Following the discovery that autosomal recessive deficiency in the DARC chemokine receptor confers resistance to Plasmodium vivax, autosomal recessive deficiencies of chemokine receptor 5 (CCR5) and the enzyme FUT2 were shown to underlie resistance to HIV-1 and noroviruses, respectively. Along the same lines, we propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.
Published: 2022

41. X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

Author: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, Pan-Hammarstrom, Qiang, Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillen, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kampe, Olle, Casanova, Jean-Laurent, Hammarstrom, Lennart, and Pan-Hammarstrom, Qiang
Abstract: Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
Published: 2022
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42. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal a-toxin

Author: MMB, Infection & Immunity, Immuno/reuma patientenzorg, MMB Research line 1, MMB Medische Staf, MS Reumatologie/Immunologie/Infectie, Medische Staf Intensive Care, Spaan, András N., Neehus, Anna Lena, Laplantine, Emmanuel, Staels, Frederik, Ogishi, Masato, Seeleuthner, Yoann, Rapaport, Franck, Lacey, Keenan A., Van Nieuwenhove, Erika, Chrabieh, Maya, Hum, David, Migaud, Mélanie, Izmiryan, Araksya, Lorenzo, Lazaro, Kochetkov, Tatiana, Heesterbeek, Dani A.C., Bardoel, Bart W., DuMont, Ashley L., Dobbs, Kerry, Chardonnet, Solenne, Heissel, Søren, Baslan, Timour, Zhang, Peng, Yang, Rui, Bogunovic, Dusan, Wunderink, Herman F., Haas, Pieter Jan A., Molina, Henrik, Van Buggenhout, Griet, Lyonnet, Stanislas, Notarangelo, Luigi D., Seppänen, Mikko R.J., Weil, Robert, Seminario, Gisela, Gomez-Tello, Héctor, Wouters, Carine, Mesdaghi, Mehrnaz, Shahrooei, Mohammad, Bossuyt, Xavier, Sag, Erdal, Topaloglu, Rezan, Ozen, Seza, Leavis, Helen L., van Eijk, Maarten M.J., Bezrodnik, Liliana, Galicia, Lizbeth Blancas, Hovnanian, Alain, Nassif, Aude, Bader-Meunier, Brigitte, Neven, Bénédicte, Meyts, Isabelle, Schrijvers, Rik, Puel, Anne, Bustamante, Jacinta, Aksentijevich, Ivona, Kastner, Daniel L., Torres, Victor J., Humblet-Baron, Stéphanie, Liston, Adrian, Abel, Laurent, Boisson, Bertrand, Casanova, Jean Laurent, MMB, Infection & Immunity, Immuno/reuma patientenzorg, MMB Research line 1, MMB Medische Staf, MS Reumatologie/Immunologie/Infectie, Medische Staf Intensive Care, Spaan, András N., Neehus, Anna Lena, Laplantine, Emmanuel, Staels, Frederik, Ogishi, Masato, Seeleuthner, Yoann, Rapaport, Franck, Lacey, Keenan A., Van Nieuwenhove, Erika, Chrabieh, Maya, Hum, David, Migaud, Mélanie, Izmiryan, Araksya, Lorenzo, Lazaro, Kochetkov, Tatiana, Heesterbeek, Dani A.C., Bardoel, Bart W., DuMont, Ashley L., Dobbs, Kerry, Chardonnet, Solenne, Heissel, Søren, Baslan, Timour, Zhang, Peng, Yang, Rui, Bogunovic, Dusan, Wunderink, Herman F., Haas, Pieter Jan A., Molina, Henrik, Van Buggenhout, Griet, Lyonnet, Stanislas, Notarangelo, Luigi D., Seppänen, Mikko R.J., Weil, Robert, Seminario, Gisela, Gomez-Tello, Héctor, Wouters, Carine, Mesdaghi, Mehrnaz, Shahrooei, Mohammad, Bossuyt, Xavier, Sag, Erdal, Topaloglu, Rezan, Ozen, Seza, Leavis, Helen L., van Eijk, Maarten M.J., Bezrodnik, Liliana, Galicia, Lizbeth Blancas, Hovnanian, Alain, Nassif, Aude, Bader-Meunier, Brigitte, Neven, Bénédicte, Meyts, Isabelle, Schrijvers, Rik, Puel, Anne, Bustamante, Jacinta, Aksentijevich, Ivona, Kastner, Daniel L., Torres, Victor J., Humblet-Baron, Stéphanie, Liston, Adrian, Abel, Laurent, Boisson, Bertrand, and Casanova, Jean Laurent
Published: 2022

43. Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease

Author: Le Voyer, Tom, Neehus, Anna Lena, Yang, Rui, Ogishi, Masato, Rosain, Jérémie, Alroqi, Fayhan, Alshalan, Maha, Blumental, Sophie, Ali, Fatima Al, Khan, Taushif, Ata, Manar, Rozen, Laurence, Demulder, Anne, Bastard, Paul, Gruber, Conor, Roynard, Manon, Seeleuthener, Yoann, Rapaport, Franck, Bigio, Benedetta, Chrabieh, Maya, Sng, Danielle, Berteloot, Laureline, Boddaert, Nathalie, Rozenberg, Flore, Al-Muhsen, Saleh, Bertoli-Avella, Aida, Abel, Laurent, Bogunovic, Dusan, Marr, Nico, Mansouri, Davood, Mutairi, Fuad Al, Béziat, Vivien, Weil, Dominique, Mahdaviani, Seyed Alireza, Ferster, Alina, Zhang, Shen Ying, Reversade, Bruno, Boisson-Dupuis, Stéphanie, Casanova, Jean-Laurent, Bustamante, Jacinta, Le Voyer, Tom, Neehus, Anna Lena, Yang, Rui, Ogishi, Masato, Rosain, Jérémie, Alroqi, Fayhan, Alshalan, Maha, Blumental, Sophie, Ali, Fatima Al, Khan, Taushif, Ata, Manar, Rozen, Laurence, Demulder, Anne, Bastard, Paul, Gruber, Conor, Roynard, Manon, Seeleuthener, Yoann, Rapaport, Franck, Bigio, Benedetta, Chrabieh, Maya, Sng, Danielle, Berteloot, Laureline, Boddaert, Nathalie, Rozenberg, Flore, Al-Muhsen, Saleh, Bertoli-Avella, Aida, Abel, Laurent, Bogunovic, Dusan, Marr, Nico, Mansouri, Davood, Mutairi, Fuad Al, Béziat, Vivien, Weil, Dominique, Mahdaviani, Seyed Alireza, Ferster, Alina, Zhang, Shen Ying, Reversade, Bruno, Boisson-Dupuis, Stéphanie, Casanova, Jean-Laurent, and Bustamante, Jacinta
Abstract: Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for ZNFX1 variants (p.S959* and p.E1606Rfs*10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs*10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

44. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Author: van der Wijst, Monique GP, van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, UCSF COMET consortium, van der Wijst, Monique GP, van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, and UCSF COMET consortium
Abstract: [Figure: see text].
Published: 2021

45. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.

Author: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Casanova, Jean-Laurent, Puel, Anne, Zhang, Qian, Cobat, Aurélie, Soumelis, Vassili, Amara, Ali, Jouanguy, Emmanuelle, Su, Helen C, Abel, Laurent, Notarangelo, Luigi D, Bastard, Paul, Lifton, Richard P, Béziat, Vivien, Zhang, Shen-Ying, Boisson-Dupuis, Stéphanie, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G, Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G, Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M, Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T, Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C I Edvard, Norlin, Anna-Carin, Campbell, Tessa M, Covill, Laura E, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N, Dalgard, Clifton L, Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid, Biobank, NIAID-USUHS COVID Study Group, Bustamante, Jacinta, Froidure, Antoine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Casanova, Jean-Laurent, Puel, Anne, Zhang, Qian, Cobat, Aurélie, Soumelis, Vassili, Amara, Ali, Jouanguy, Emmanuelle, Su, Helen C, Abel, Laurent, Notarangelo, Luigi D, Bastard, Paul, Lifton, Richard P, Béziat, Vivien, Zhang, Shen-Ying, Boisson-Dupuis, Stéphanie, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G, Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G, Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M, Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T, Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C I Edvard, Norlin, Anna-Carin, Campbell, Tessa M, Covill, Laura E, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N, Dalgard, Clifton L, Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid, Biobank, NIAID-USUHS COVID Study Group, Bustamante, Jacinta, and Froidure, Antoine
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such variants ( = 3.5 × 10). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (=2, 5 and 38 years), or moderate (=1, 5 years), severe (=1, 27 years), or critical (=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious variants in the male general population is < 6.5x10 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.
Published: 2021

46. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.

Author: UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G, Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G, Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M, Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T, Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C I Edvard, Norlin, Anna-Carin, Campbell, Tessa M, Covill, Laura E, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N, Dalgard, Clifton L, Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid, Biobank, NIAID-USUHS COVID Study Group, Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P, Bastard, Paul, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Froidure, Antoine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J, Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G, Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G, Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M, Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E, de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T, Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C I Edvard, Norlin, Anna-Carin, Campbell, Tessa M, Covill, Laura E, Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N, Dalgard, Clifton L, Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L, COVID Human Genetic Effort, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid, Biobank, NIAID-USUHS COVID Study Group, Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P, Bastard, Paul, Notarangelo, Luigi D, Abel, Laurent, Su, Helen C, Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, and Froidure, Antoine
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such variants ( = 3.5 × 10). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (=2, 5 and 38 years), or moderate (=1, 5 years), severe (=1, 27 years), or critical (=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious variants in the male general population is < 6.5x10 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.
Published: 2021

47. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Author: van der Wijst, Monique GP, van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, UCSF COMET consortium, van der Wijst, Monique GP, van der Wijst, Monique GP, Vazquez, Sara E, Hartoularos, George C, Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S, Greenland, John R, Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A, Lynch, Kara L, Yun, Cassandra, Havlir, Diane V, Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S, Norris, Philip J, Dumont, Larry J, Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J, Rao, Arjun Arkal, Song, Yun S, Fragiadakis, Gabriela K, Kangelaris, Kirsten, Calfee, Carolyn S, Erle, David J, Hendrickson, Carolyn, Krummel, Matthew F, Woodruff, Prescott G, Langelier, Charles R, Casanova, Jean-Laurent, Derisi, Joseph L, Anderson, Mark S, Ye, Chun Jimmie, and UCSF COMET consortium
Abstract: Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.
Published: 2021

48. Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance.

Author: Asano, Takaki, Asano, Takaki, Khourieh, Joëlle, Zhang, Peng, Rapaport, Franck, Spaan, András N, Li, Juan, Lei, Wei-Te, Pelham, Simon J, Hum, David, Chrabieh, Maya, Han, Ji Eun, Guérin, Antoine, Mackie, Joseph, Gupta, Sudhir, Saikia, Biman, Baghdadi, Jamila EI, Fadil, Ilham, Bousfiha, Aziz, Habib, Tanwir, Marr, Nico, Ganeshanandan, Luckshman, Peake, Jane, Droney, Luke, Williams, Andrew, Celmeli, Fatih, Hatipoglu, Nevin, Ozcelik, Tayfun, Picard, Capucine, Abel, Laurent, Tangye, Stuart G, Boisson-Dupuis, Stéphanie, Zhang, Qian, Puel, Anne, Béziat, Vivien, Casanova, Jean-Laurent, Boisson, Bertrand, Asano, Takaki, Asano, Takaki, Khourieh, Joëlle, Zhang, Peng, Rapaport, Franck, Spaan, András N, Li, Juan, Lei, Wei-Te, Pelham, Simon J, Hum, David, Chrabieh, Maya, Han, Ji Eun, Guérin, Antoine, Mackie, Joseph, Gupta, Sudhir, Saikia, Biman, Baghdadi, Jamila EI, Fadil, Ilham, Bousfiha, Aziz, Habib, Tanwir, Marr, Nico, Ganeshanandan, Luckshman, Peake, Jane, Droney, Luke, Williams, Andrew, Celmeli, Fatih, Hatipoglu, Nevin, Ozcelik, Tayfun, Picard, Capucine, Abel, Laurent, Tangye, Stuart G, Boisson-Dupuis, Stéphanie, Zhang, Qian, Puel, Anne, Béziat, Vivien, Casanova, Jean-Laurent, and Boisson, Bertrand
Abstract: Most patients with autosomal dominant hyper-IgE syndrome (AD-HIES) carry rare heterozygous STAT3 variants. Only six of the 135 in-frame variants reported have been experimentally shown to be dominant negative (DN), and it has been recently suggested that eight out-of-frame variants operate by haploinsufficiency. We experimentally tested these 143 variants, 7 novel out-of-frame variants found in HIES patients, and other STAT3 variants from the general population. Strikingly, all 15 out-of-frame variants were DN via their encoded (1) truncated proteins, (2) neoproteins generated from a translation reinitiation codon, and (3) isoforms from alternative transcripts or a combination thereof. Moreover, 128 of the 135 in-frame variants (95%) were also DN. The patients carrying the seven non-DN STAT3 in-frame variants have not been studied for other genetic etiologies. Finally, none of the variants from the general population tested, including an out-of-frame variant, were DN. Overall, our findings show that heterozygous STAT3 variants, whether in or out of frame, underlie AD-HIES through negative dominance rather than haploinsufficiency.
Published: 2021

49. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Author: Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, Casanova, J, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, Casanova, J, Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Christèle, Kyheng, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., de Diego, Rebeca Pérez, Keles, Sevgi, Aytekin, Gokhan, Akcan, Ozge Metin, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, and Casanova, Jean-Laurent
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10−4. We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.
Published: 2021

50. Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19

Author: Abers, M, Rosen, L, Delmonte, O, Shaw, E, Bastard, P, Imberti, L, Quaresima, V, Biondi, A, Bonfanti, P, Castagnoli, R, Casanova, J, Su, H, Notarangelo, L, Holland, S, Lionakis, M, Abers, Michael S, Rosen, Lindsey B, Delmonte, Ottavia M, Shaw, Elana, Bastard, Paul, Imberti, Luisa, Quaresima, Virginia, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Casanova, Jean-Laurent, Su, Helen C, Notarangelo, Luigi D, Holland, Steven M, Lionakis, Michail S, Abers, M, Rosen, L, Delmonte, O, Shaw, E, Bastard, P, Imberti, L, Quaresima, V, Biondi, A, Bonfanti, P, Castagnoli, R, Casanova, J, Su, H, Notarangelo, L, Holland, S, Lionakis, M, Abers, Michael S, Rosen, Lindsey B, Delmonte, Ottavia M, Shaw, Elana, Bastard, Paul, Imberti, Luisa, Quaresima, Virginia, Biondi, Andrea, Bonfanti, Paolo, Castagnoli, Riccardo, Casanova, Jean-Laurent, Su, Helen C, Notarangelo, Luigi D, Holland, Steven M, and Lionakis, Michail S
Abstract: Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms that contribute to illness severity remains unclear. In the present study, our goal was to gain insight into how type-I IFNs influence patient outcomes in patients with COVID-19. To achieve this goal, we compared clinical outcomes between 26 patients with neutralizing type-I IFN autoantibodies (AAbs) and 192 patients without AAbs who were hospitalized for COVID-19 at three Italian hospitals. The presence of circulating AAbs to type-I IFNs was associated with an increased risk of admission to the intensive care unit and a delayed time to viral clearance. However, survival was not adversely affected by the presence of type-I IFN AAbs. Our findings provide further support for the contribution of type-I IFN AAbs in impairing host antiviral defense and promoting the development of critical COVID-19 pneumonia in SARS-CoV-2-infected individuals.
Published: 2021

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