Infections in the monogenic autoimmune syndrome APECED

Curr Opin Immunol. 2021 Oct:72:286-297. doi: 10.1016/j.coi.2021.07.011. Epub 2021 Aug 18.

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune Regulator (AIRE) gene, which impair the thymic negative selection of self-reactive T-cells and underlie the development of autoimmunity that targets multiple endocrine and non-endocrine tissues. Beyond autoimmunity, APECED features heightened susceptibility to certain specific infections, which is mediated by anti-cytokine autoantibodies and/or T-cell driven autoimmune tissue injury. These include the 'signature' APECED infection chronic mucocutaneous candidiasis (CMC), but also life-threatening coronavirus disease 2019 (COVID-19) pneumonia, bronchiectasis-associated bacterial pneumonia, and sepsis by encapsulated bacteria. Here we discuss the expanding understanding of the immunological mechanisms that contribute to infection susceptibility in this prototypic syndrome of impaired central tolerance, which provide the foundation for devising improved diagnostic and therapeutic strategies for affected patients.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • AIRE Protein
  • Animals
  • Autoimmunity
  • Bronchiectasis
  • COVID-19 / epidemiology
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • Candidiasis, Cutaneous / epidemiology
  • Candidiasis, Cutaneous / genetics
  • Candidiasis, Cutaneous / immunology*
  • Clonal Selection, Antigen-Mediated / genetics
  • Disease Susceptibility
  • Humans
  • Immune Tolerance / genetics
  • Polyendocrinopathies, Autoimmune / epidemiology
  • Polyendocrinopathies, Autoimmune / genetics
  • Polyendocrinopathies, Autoimmune / immunology*
  • T-Lymphocytes / immunology*
  • Transcription Factors / genetics*

Substances

  • Transcription Factors