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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Journal of experimental medicine. - 221, 11 (2024) , e20231152, ISSN: 1540-9538
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2024
- Creator
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Rosain, Jérémie
Has, Cristina
Hübner, Stefanie
Bastard, Paul
Landegren, Nils
Anderson, Mark S.
Casanova, Jean-Laurent
- DOI
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10.1084/jem.20231152
- URN
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urn:nbn:de:bsz:25-freidok-2587006
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:38 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Rosain, Jérémie
- Has, Cristina
- Hübner, Stefanie
- Bastard, Paul
- Landegren, Nils
- Anderson, Mark S.
- Casanova, Jean-Laurent
- Universität
Time of origin
- 2024
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