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

: Hetemäki Iivo, Laakso Saila, Välimaa Hannamari, Kleino Iivari, Kekäläinen Eliisa, Mäkitie Outi, Arstila T. Petteri

: 2021

: Clinical Immunology

: Clinical immunology (Orlando, Fla.)

: Clin Immunol

: 108851

: 231

: 1521-6616

: 1521-7035

DOI: https://doi.org/10.1016/j.clim.2021.108851

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.