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

Iivo Hetemäki; Saila Laakso; Hannamari Välimaa; Iivari Kleino; Eliisa Kekäläinen; Outi Mäkitie; T Petteri Arstila

doi:10.1016/j.clim.2021.108851

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

Clin Immunol. 2021 Oct:231:108851. doi: 10.1016/j.clim.2021.108851. Epub 2021 Sep 8.

Authors

Iivo Hetemäki¹, Saila Laakso², Hannamari Välimaa³, Iivari Kleino⁴, Eliisa Kekäläinen⁵, Outi Mäkitie⁶, T Petteri Arstila⁵

Affiliations

¹ Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address: iivo.hetemaki@helsinki.fi.
² Folkhälsan Institute of Genetics, Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
³ Department of Virology, University of Helsinki, Helsinki, Finland; Department of Oral and Maxillofacial Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁴ Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁵ Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁶ Folkhälsan Institute of Genetics, Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Molecular Medicine, Karolinska Institutet, Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

Abstract

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.

Keywords: AIRE; Autoantibody; Herpes simplex; Herpes zoster; Immunodeficiency; Type I interferon; Varicella zoster.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Child
Cohort Studies
Female
Herpesvirus 3, Human*
Humans
Immunity, Cellular
Interferon-alpha / immunology
Male
Middle Aged
Polyendocrinopathies, Autoimmune / complications*
Polyendocrinopathies, Autoimmune / immunology
Risk Factors
Varicella Zoster Virus Infection / complications*
Varicella Zoster Virus Infection / pathology
Young Adult

Substances

Interferon-alpha

Supplementary concepts

Autoimmune polyendocrinopathy syndrome, type 1