The following is a summary of “Dysregulated germinal center reaction with expanded T follicular helper cells in autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy lymph nodes,” published in the May 2024 issue of Allergy & Immunology by Hetemäki, et al.

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED, also known as APS-1) is a genetic immune disorder marked by distinct B-cell autoimmunity, including the presence of neutralizing anti-IFN antibodies. Mutations in the AIRE gene associated with APECED disrupt the thymic negative selection of T cells, potentially leading to dysregulated B-cell responses. However, interactions between T and B cells within germinal centers (GCs) of patients’ secondary lymphatic tissues have not been previously explored. For a study, researchers sought to investigate the relationship between B cells and follicular T helper cells (TfH) in the peripheral blood and lymph node (LN) germinal centers of patients with APECED.

24 patients with APECED were immunophenotyping peripheral blood B cells and TfH cells. Additionally, highly multiplexed fluorescent immunohistochemical staining was utilized on 7 LN biopsy samples from these patients to analyze the spatial interactions of lymphocytes within the GCs at the single-cell level.

Peripheral B-cell analysis revealed a skewing towards a mature B-cell phenotype, with a notable reduction in transitional and naive B cells. While the frequency of circulating TfH cells was diminished, the TfH population in LNs was expanded. Furthermore, the frequency of Treg cells and their interactions with nonfollicular T cells were reduced in the LNs, suggesting an impairment in Treg cell function, potentially failing to limit TfH differentiation.

Germinal center reactions in APECED are disrupted due to defective T-cell control mechanisms. The disruption is characterized by altered B-cell phenotypes and dysfunctional interactions between Treg cells and TfH cells, highlighting the complex immune dysregulation in patients with APECED.

Reference: jacionline.org/article/S0091-6749(23)02454-5/fulltext