Rare genetic condition links immune system breakdown to severe viral vulnerability
Researchers found that over one-third of women with incontinentia pigmenti—a rare X-linked genetic disorder—develop antibodies that disable their natural antiviral defenses, leaving them exposed to life-threatening infections. The discovery identifies a new mechanism linking genetic thymus damage to autoimmune disease and could redirect vaccine and immunotherapy strategies for at-risk populations.
Originaltitel: Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases
<p>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.</p>