Immune cell subsets in autoimmune polyendocrine syndrome type I

Autoimmune Polyendocrine Syndrome Type 1 (APS-I) results from mutations in the Autoimmune Regulator (AIRE) gene and serves as a valuable model to understand autoimmunity and immune deficiency. Various studies have produced differing results on how AIRE dysfunction affects the balance of immune cell subsets in blood in humans. We conducted high-resolution whole blood immune cell subset analysis using a 36-panel mass cytometry assay in Norwegian APS-I patients (N = 18) and compared with age and sex-matched healthy subjects (N = 19). Additionally, we provide a comprehensive summary of findings from 28 other studies examining blood immune subset distributions in APS-I patients. Norwegian APS-I patients had significantly reduced numbers of B cells, which was driven by lower levels of the naïve and transitional B cell compartments. We further observed trends indicating reduced frequencies of NK cells, as well as deviations in CD16-expressing cells in several subsets in APS-I patients. Contrary to previous reports, our study did not find differences in regulatory T cell levels between APS-I patients and healthy controls. Several studies in our summary consistently reported lower frequencies of resting naïve B cells in APS-I patients and higher proportions of activated memory B cells in APS-I patients. The composition of other immune cell subsets was more diverse between studies, probably reflecting contributions by other factors like medications, ethnicity, disease complexity, insufficient sample sizes, time of sampling, ages, unique immune profiles and health conditions of the patients and controls. Future research should prioritize investigating antigen-specific responses in blood and tissues to further illuminate this complex area.