Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections

Almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) have neutralizing antibodies against type 1 interferons (IFN), important mediators of antiviral defense. Recently, neutralizing anti-IFN antibodies were shown to be a risk factor of severe COVID-19. Here we show in a cohort of 44 patients with APS-1 that higher titers of neutralizing anti-IFNα4 antibodies are associated with a higher and earlier incidence of VZV reactivation (herpes zoster). The patients also present with uncommonly severe clinical sequelae of herpetic infections. APS-1 patients had decreased humoral immune responses to varicella zoster virus, but cellular responses were comparable to healthy controls. These results suggest that blocking the type I interferon pathway in patients with APS-1 patients leads to a clinically significant immune deficiency, and susceptibility to herpesviruses should be taken into account when treating patients with APS-1. •Patients with APS-1 have high incidence of VZV reactivation.•VZV reactivations are associated with high neutralizing anti-interferon antibody titers.•The patients have decreased humoral immune responses to varicella zoster virus.•The patients often present with severe clinical sequelae of herpesvirus infections.