Article
作者: Charmeteau-De Muylder, Bénédicte ; Lambert, Nathalie ; Béziat, Vivien ; Welfringer-Morin, Anne ; Cheynier, Rémi ; Lévy, Romain ; Bizien, Lucy ; Bastard, Paul ; Yasumi, Takahiro ; Dorgham, Karim ; Deswarte, Caroline ; Sacko-Sow, Aissata ; Materna, Marie ; Gao, Liwei ; Taniguchi, Maki ; Le Floc’h, Corentin ; Boisson, Bertrand ; Martinovic, Jelena ; Marr, Nico ; Blanchard-Rohner, Géraldine ; Rozenberg, Flore ; Steffann, Julie ; Berteloot, Laureline ; Khan, Taushif ; Soudais, Claire ; Poziomczyk, Cláudia S. ; Hadj-Rabia, Smail ; Pasparakis, Manolis ; Minic, Snezana ; Rosain, Jérémie ; Hadjem, Lillia ; Roelens, Marie ; Desguerre, Isabelle ; Philippot, Quentin ; Esnaola Azcoiti, Maria ; Fauvarque, Marie-Odile ; Li, Hailun ; Utsumi, Takanori ; Abel, Laurent ; Aubart, Mélodie ; Picard, Capucine ; Le Voyer, Tom ; Fekkar, Arnaud ; Parent, Audrey V. ; Rheault, Sylvie ; Gervais, Adrian ; Geraldo, Amyrath ; Muti, Christine ; Kanai, Sotaro ; Has, Cristina ; Boucherit, Soraya ; Migaud, Mélanie ; Catherinot, Emilie ; Bustamante, Jacinta ; Tani, Hiroo ; Bodemer, Christine ; Pescatore, Alessandra ; Casanova, Jean-Laurent ; Neehus, Anna-Lena ; Eriksson, Daniel ; L’Honneur, Anne-Sophie ; Luche, Hervé ; Pellegrini, Silvia ; Hübner, Stefanie ; Ursini, Matilde Valeria ; Milner, Joshua D. ; Bobrie-Moyrand, Claire ; Marchal, Astrid ; Courtois, Gilles ; Ünal, Sinem ; Kiszewski, Ana Elisa ; Trpinac, Dusan ; Fusco, Francesca ; Cederholm, Axel ; Landegren, Nils ; Okada, Satoshi ; Piemonti, Lorenzo ; Falcone, Emilia Liana ; Liu, Xian ; Soudée, Camille ; Goffard, Jean-Christophe ; Puel, Mathilde ; Cobat, Aurélie ; Izawa, Kazushi ; Jouanguy, Emmanuelle ; Fuleihan, Ramsay L. ; Spinosa, Ezia ; Vabres, Pierre ; Boddaert, Nathalie ; Zhang, Shen-Ying ; Zhang, Qian ; Polivka, Laura ; Thibault, Chloé ; Tsumura, Miyuki ; Miller, Corey N. ; Gorochov, Guy ; Amador-Borrero, Blanca ; Anderson, Mark S. ; Puel, Anne
Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases.