The rise in prevalence of autoantibodies neutralizing type I interferons reaches a plateau in centenarians

While autoantibodies (auto-Abs) neutralizing type I interferons (IFN-I) are relatively rare before the age of 65 (<1%), their prevalence reaches 2-3% between 70 and 80 years and >6% in individuals above 80 years in the general population. To assess the prevalence of IFN-I auto-Abs at the extreme end of human lifespan, we performed a multinational study of centenarians from four geographically and ethnically distinct cohorts collected in Denmark (n = 258), Colombia (n = 99), Australia (n = 281), and Japan (n = 300), comprising 938 individuals. Across cohorts, 51/938 centenarians (5.4%) harbored auto-Abs neutralizing IFN-I, ranging from 3.3% (Japan) to 9.1% (Colombia). We found that the prevalence of IFN-I auto-Abs levels off in centenarians compared with individuals ≥80 years from the general population, demonstrating that neutralizing IFN-I auto-Abs are not incompatible with longevity, despite conferring a risk of life-threatening viral infections. Yet, the plateau of their prevalence in centenarians suggests that they may not be beneficial for reaching exceptional longevity and may negatively impact mortality.