Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases
Archive ouverte
Rosain, Jérémie | Le Voyer, Tom | Liu, Xian | Gervais, Adrian | Polivka, Laura | Cederholm, Axel | Berteloot, Laureline | Parent, Audrey, V | Pescatore, Alessandra | Spinosa, Ezia | Minic, Snezana | Kiszewski, Ana Elisa | Tsumura, Miyuki | Thibault, Chloé | Esnaola Azcoiti, Maria | Martinovic, Jelena | Philippot, Quentin | Khan, Taushif | Marchal, Astrid | Charmeteau-de Muylder, Bénédicte | Bizien, Lucy | Deswarte, Caroline | Hadjem, Lillia | Fauvarque, Marie-Odile | Dorgham, Karim | Eriksson, Daniel | Falcone, Emilia Liana | Puel, Mathilde | Ünal, Sinem | Geraldo, Amyrath | Le Floc’h, Corentin | Li, Hailun | Rheault, Sylvie | Muti, Christine | Bobrie-Moyrand, Claire | Welfringer-Morin, Anne | Fuleihan, Ramsay, L | Lévy, Romain | Roelens, Marie | Gao, Liwei | Materna, Marie | Pellegrini, Silvia | Piemonti, Lorenzo | Catherinot, Emilie | Goffard, Jean-Christophe | Fekkar, Arnaud | Sacko-Sow, Aissata | Soudée, Camille | Boucherit, Soraya | Neehus, Anna-Lena | Has, Cristina | Hübner, Stefanie | Blanchard-Rohner, Géraldine | Amador-Borrero, Blanca | Utsumi, Takanori | Taniguchi, Maki | Tani, Hiroo | Izawa, Kazushi | Yasumi, Takahiro | Kanai, Sotaro | Migaud, Mélanie | Aubart, Mélodie | Lambert, Nathalie | Gorochov, Guy | Picard, Capucine | Soudais, Claire | L’honneur, Anne-Sophie | Rozenberg, Flore | Milner, Joshua, D | Zhang, Shen-Ying | Vabres, Pierre | Trpinac, Dusan | Marr, Nico | Boddaert, Nathalie | Desguerre, Isabelle | Pasparakis, Manolis | Miller, Corey, N | Poziomczyk, Cláudia, S | Abel, Laurent | Okada, Satoshi | Jouanguy, Emmanuelle | Cheynier, Rémi | Zhang, Qian | Cobat, Aurélie | Béziat, Vivien | Boisson, Bertrand | Steffann, Julie | Fusco, Francesca | Ursini, Matilde Valeria | Hadj-Rabia, Smail | Bodemer, Christine | Bustamante, Jacinta | Luche, Hervé | Puel, Anne | Courtois, Gilles | Bastard, Paul | Landegren, Nils | Anderson, Mark, S | Casanova, Jean-Laurent
Edité par
CCSD ; Rockefeller University Press -
International audience.
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.
