Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases.

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. © 2024 Rosain et al.

Citation

Jérémie Rosain, Tom Le Voyer, Xian Liu, Adrian Gervais, Laura Polivka, Axel Cederholm, Laureline Berteloot, Audrey V Parent, Alessandra Pescatore, Ezia Spinosa, Snezana Minic, Ana Elisa Kiszewski, Miyuki Tsumura, Chloé Thibault, Maria Esnaola Azcoiti, Jelena Martinovic, Quentin Philippot, Taushif Khan, Astrid Marchal, Bénédicte Charmeteau-De Muylder, Lucy Bizien, Caroline Deswarte, Lillia Hadjem, Marie-Odile Fauvarque, Karim Dorgham, Daniel Eriksson, Emilia Liana Falcone, Mathilde Puel, Sinem Ünal, Amyrath Geraldo, Corentin Le Floc'h, Hailun Li, Sylvie Rheault, Christine Muti, Claire Bobrie-Moyrand, Anne Welfringer-Morin, Ramsay L Fuleihan, Romain Lévy, Marie Roelens, Liwei Gao, Marie Materna, Silvia Pellegrini, Lorenzo Piemonti, Emilie Catherinot, Jean-Christophe Goffard, Arnaud Fekkar, Aissata Sacko-Sow, Camille Soudée, Soraya Boucherit, Anna-Lena Neehus, Cristina Has, Stefanie Hübner, Géraldine Blanchard-Rohner, Blanca Amador-Borrero, Takanori Utsumi, Maki Taniguchi, Hiroo Tani, Kazushi Izawa, Takahiro Yasumi, Sotaro Kanai, Mélanie Migaud, Mélodie Aubart, Nathalie Lambert, Guy Gorochov, Capucine Picard, Claire Soudais, Anne-Sophie L'Honneur, Flore Rozenberg, Joshua D Milner, Shen-Ying Zhang, Pierre Vabres, Dusan Trpinac, Nico Marr, Nathalie Boddaert, Isabelle Desguerre, Manolis Pasparakis, Corey N Miller, Cláudia S Poziomczyk, Laurent Abel, Satoshi Okada, Emmanuelle Jouanguy, Rémi Cheynier, Qian Zhang, Aurélie Cobat, Vivien Béziat, Bertrand Boisson, Julie Steffann, Francesca Fusco, Matilde Valeria Ursini, Smail Hadj-Rabia, Christine Bodemer, Jacinta Bustamante, Hervé Luche, Anne Puel, Gilles Courtois, Paul Bastard, Nils Landegren, Mark S Anderson, Jean-Laurent Casanova. Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases. The Journal of experimental medicine. 2024 Nov 04;221(11)

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PMID: 39352576

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