Autoantibodies neutralizing type I interferons in older twin pairs: Low concordance.

Abstract

Autoantibodies (auto-Abs) neutralizing type I interferons (IFN-I) underlie various life-threatening viral infections, and the prevalence of these auto-Abs rises sharply between 65 and 70 years of age. We investigated the familial aggregation of neutralizing IFN-I auto-Abs by assessing concordance rates in Danish older twins, including 3,270 twins aged 65-96 years in a sample comprising 1,318 intact twin pairs (2,636 individuals) and 634 twins from broken twin pairs (634 individuals). Neutralizing IFN-I auto-Abs were detected in 1.5% (50/3,270) of all twins tested, including 1.4% (37/2,636) in twins from intact pairs and 2.1% (13/634) in twins from broken pairs. A total of 50 twins had neutralizing IFN-I auto-Abs, including one concordant monozygotic pair and 35 discordant pairs, yielding a low overall concordance rate. A slight, but nonsignificant, increase in mortality was associated with harboring neutralizing IFN-I auto-Abs. Collectively, these findings do not reveal any familial aggregation of IFN-I auto-Abs, arguing against a strong germline genetic etiology of IFN-I auto-Abs in older adults.