1. Infections in the monogenic autoimmune syndrome APECED.
- Author
-
Oikonomou V, Break TJ, Gaffen SL, Moutsopoulos NM, and Lionakis MS
- Subjects
- Animals, Autoimmunity, Bronchiectasis, COVID-19 epidemiology, COVID-19 genetics, Candidiasis, Cutaneous epidemiology, Candidiasis, Cutaneous genetics, Clonal Selection, Antigen-Mediated genetics, Disease Susceptibility, Humans, Immune Tolerance genetics, Polyendocrinopathies, Autoimmune epidemiology, Polyendocrinopathies, Autoimmune genetics, AIRE Protein, COVID-19 immunology, Candidiasis, Cutaneous immunology, Polyendocrinopathies, Autoimmune immunology, T-Lymphocytes immunology, Transcription Factors genetics
- 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., (Published by Elsevier Ltd.)
- Published
- 2021
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