{"doi":"10.1084/jem.20231152","title":"Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases","abstract":"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.","journal":"The Journal of Experimental Medicine","year":2024,"id":426646,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":618891,"name":"Tom Le Voyer","orcid":"0000-0002-7253-3135","position":1,"is_corresponding":false},{"id":1019801,"name":"Xian Liu","orcid":"0000-0001-6546-3725","position":2,"is_corresponding":false},{"id":615375,"name":"Adrian Gervais","orcid":"0000-0002-1083-5787","position":3,"is_corresponding":false},{"id":1226058,"name":"Laura Polivka","orcid":"0000-0002-5142-6234","position":4,"is_corresponding":false},{"id":1019802,"name":"Axel Cederholm","orcid":"0009-0006-5973-9637","position":5,"is_corresponding":false},{"id":642456,"name":"Laureline Berteloot","orcid":"0000-0001-9681-3142","position":6,"is_corresponding":false},{"id":312358,"name":"Audrey V. 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