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

Title: Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases
Authors: Rosain, Jeremie; 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, Chloe; Azcoiti, Maria Esnaola; Martinovic, Jelena; Philippot, Quentin; Khan, Taushif; Marchal, Astrid; Charmeteau-De Muylder, Benedicte; Bizien, Lucy; Deswarte, Caroline; Hadjem, Lillia; Fauvarque, Marie-Odile; Dorgham, Karim; Eriksson, Daniel; Falcone, Emilia Liana; Puel, Mathilde; Uenal, Sinem; Geraldo, Amyrath; Le Floc'h, Corentin; Li, Hailun; Rheault, Sylvie; Muti, Christine; Bobrie-Moyrand, Claire; Welfringer-Morin, Anne; Fuleihan, Ramsay L.; Levy, Romain; Roelens, Marie; Gao, Liwei; Materna, Marie; Pellegrini, Silvia; Piemonti, Lorenzo; Catherinot, Emilie; Goffard, Jean-Christophe; Fekkar, Arnaud; Sacko-Sow, Aissata; Soudee, Camille; Boucherit, Soraya; Neehus, Anna-Lena; Has, Cristina; Huebner, Stefanie; Blanchard-Rohner, Geraldine; Amador-Borrero, Blanca; Utsumi, Takanori; Taniguchi, Maki; Tani, Hiroo; Izawa, Kazushi; Yasumi, Takahiro; Kanai, Sotaro; Migaud, Melanie; Aubart, Melodie; 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, Claudia S.; Abel, Laurent; Okada, Satoshi; Jouanguy, Emmanuelle; Cheynier, Remi; Zhang, Qian; Cobat, Aurelie; Beziat, Vivien; Boisson, Bertrand; Steffann, Julie; Fusco, Francesca; Ursini, Matilde Valeria; Hadj-Rabia, Smail; Bodemer, Christine; Bustamante, Jacinta; Luche, Herve; Puel, Anne; Courtois, Gilles; Bastard, Paul; Landegren, Nils; Anderson, Mark S.; Casanova, Jean-Laurent
Publisher Information: Uppsala universitet, Science for Life Laboratory, SciLifeLab; Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi; Uppsala universitet, Institutionen för immunologi, genetik och patologi; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.;Necker Hosp Sick Children, Assistance Publ Hop Paris AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.;St Louis Hosp, AP HP, Clin Immunol Dept, Paris, France.; Univ Calif San Francisco, Diabet Ctr, San Francisco, CA USA.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.; Univ Paris Cite, Necker Hosp Sick Children, Reference Ctr Genodermatosis & Rare Skin Dis MAGE, Dept Dermatol,AP HP, F-75015 Paris, France.;Necker Hosp Sick Children, AP HP, Reference Ctr Mastocytosis CEREMAST, Paris, France.; Necker Hosp Sick Children, AP HP, Pediat Radiol Dept, U1163,Imagine Inserm Inst, Paris, France.; IGB CNR, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy.; Clin Ctr Serbia, Clin Dermatovenerol, Belgrade, Serbia.;Univ Belgrade, Sch Med, Belgrade, Serbia.; Fed Univ Hlth Sci Porto Alegre, Sect Dermatol, Porto Alegre, Brazil.;Hosp Crianca Santo Antonio, Sect Pediat Dermatol, Irmandade Santo Casa Misericordia Porto Alegre, Porto Alegre, Brazil.; Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan.; Paris Saclay Univ, Hosp Antoine Beclere, Unit Fetal Pathol, Paris, France.; Sidra Med, Dept Immunol, Doha, Qatar.; Univ Paris Cite, Inst Cochin, CNRS, INSERM, Paris, France.; Aix Marseille Univ, Immunophen Ctr CIPHE, INSERM, CNRS, Marseille, France.; Univ Grenoble Alpes, CEA, INSERM, BGE UA13, Grenoble, France.; Sorbonne Univ, Ctr Immunol & Microbial Infect, CIMI Paris, INSERM, Paris, France.; Montreal Clin Res Inst IRCM, Ctr Immun Inflammat & Infect Dis, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Montreal, PQ, Canada.; Necker Hosp Sick Children, Assistance Publ Hop Paris AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.; Univ Montreal, Dept Med, Montreal, PQ, Canada.;Univ Montreal, Ctr Res Geriatr Univ Inst Montreal, Montreal, PQ, Canada.; Andre Mignot Hosp, Dept Genet, Versailles, France.; Andre Mignot Hosp, Dept Obstet & Gynecol, Versailles, France.; Univ Paris Cite, Necker Hosp Sick Children, Reference Ctr Genodermatosis & Rare Skin Dis MAGE, Dept Dermatol,AP HP, F-75015 Paris, France.; Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.;Necker Hosp Sick Children, AP HP, Pediat Hematol Immunol & Rheumatol Unit, Paris, France.; Univ Paris Cite, Imagine Inst, Paris, France.;Necker Hosp Sick Children, Assistance Publ Hop Paris AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.; IRCCS Osped San Raffaele, Diabet Res Inst, Milan, Italy.; Foch Hosp, Dept Resp Dis, Suresnes, France.; Free Univ Brussels, Brussels Univ Hosp, Internal Med, Anderlecht, Belgium.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Hop La Pitie Salpetriere, AP HP, Dept Parasitol Mycol, Paris, France.; Jean Verdier Hosp, AP HP, Dept Pediat, Bondy, France.; Univ Freiburg, Med Ctr, Dept Dermatol, Freiburg, Germany.;European Reference Network ERN Rare & Undiagnosed, Paris, France.; Univ Freiburg, Med Ctr, Dept Dermatol, Freiburg, Germany.; Geneva Univ Hosp, Div Gen Pediat, Dept Woman Child & Adolescent Med, Unit Immunol Vaccinol & Rheumatol, Geneva, Switzerland.;Univ Geneva, Fac Med, Geneva, Switzerland.; Univ Paris Cite, Lariboisiere Hosp, AP HP, Internal Med Dept, Paris, France.; Hiroshima Univ Hosp, Dept Pediat, Hiroshima, Japan.;Hiroshima Prefectural Hosp, Dept Pediat, Hiroshima, Japan.; Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto, Japan.; Tottori Univ, Div Child Neurol, Dept Brain & Neurosci, Fac Med, Yonago, Japan.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Univ Paris Cite, AP HP, Necker Hosp Sick Children, Dept Pediat Neurol, Paris, France.; Sorbonne Univ, Ctr Immunol & Microbial Infect, CIMI Paris, INSERM, Paris, France.;Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris, France.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Necker Hosp Sick Children, Assistance Publ Hop Paris AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.;INSERM, Lab Lymphocyte Activat & Susceptibil EBV Infect, U1163, Paris, France.; INSERM, Lab Lymphocyte Activat & Susceptibil EBV Infect, U1163, Paris, France.; Univ Paris Cite, Dept Virol, Paris, France.;Cochin Hosp, AP HP, Paris, France.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.; Dijon Bourgogne Univ Hosp, MAGEC Reference Ctr Rare Skin Dis, Dijon, France.; Univ Belgrade, Inst Histol & Embryol, Sch Med, Belgrade, Serbia.; Sidra Med, Dept Immunol, Doha, Qatar.;Hamad Bin Khalifa Univ, Coll Hlth & Life Sci, Doha, Qatar.; Univ Paris Cite, AP HP, Necker Hosp Sick Children, Dept Pediat Neurol, Paris, France.; Univ Cologne, Inst Genet, Cologne, Germany.; Private Dermatol Practice, Porto Alegre, RS, Brazil.; Univ Paris Cite, Necker Hosp Sick Children, AP HP, Dept Genom Med, Paris, France.; Uppsala Univ, Sci Life Lab, Dept Med Biochem & Microbiol, Uppsala, Sweden.;Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.; Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM,U1163, Paris, France.;Univ Paris Cite, Imagine Inst, Paris, France.;Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.;Necker Hosp Sick Children, AP HP, Dept Pediat, Paris, France.;Howard Hughes Med Inst, New York, NY 10032 USA.
Publication Year: 2024
Collection: Uppsala University: Publications (DiVA)
Subject Terms: Immunology in the medical area; Immunologi inom det medicinska området; Clinical Medicine; Klinisk medicin; Pediatrics; Pediatrik
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-alpha and/or IFN-omega, 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
File Description: application/pdf
Language: English
Relation: Journal of Experimental Medicine, 0022-1007, 2024, 221:11; PMID 39352576; ISI:001326891400001
DOI: 10.1084/jem.20231152
Availability: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540695; https://doi.org/10.1084/jem.20231152
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.40966F84
Database: BASE