| Title: |
Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases |
| Authors: |
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 |
| Source: |
ISSN: 0022-1007 ; The Journal of experimental medicine, vol. 221, no. 11 (2024) e20231152. |
| Publication Year: |
2024 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/618; Humans; Interferon Type I / immunology; Interferon Type I / metabolism; Female; Autoantibodies / immunology; Thymus Gland / immunology; Thymus Gland / pathology; Child; Incontinentia Pigmenti / immunology; Incontinentia Pigmenti / genetics; Incontinentia Pigmenti / pathology; Preschool; I-kappa B Kinase / genetics; I-kappa B Kinase / immunology; Virus Diseases / immunology; Infant; Adult; Adolescent; Young Adult |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39352576; unige:189138 |
| Availability: |
https://archive-ouverte.unige.ch/unige:189138 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.A36C9014 |
| Database: |
BASE |