B Cells and Autoantibodies in AIRE Deficiency.

Anette S B Wolff,Bergithe E Oftedal,Sarah Braun,Eystein S Husebye

doi:10.3390/biomedicines9091274

Abstract

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare but severe monogenetic autoimmune endocrine disease caused by failure of the Autoimmune Regulator (AIRE). AIRE regulates the negative selection of T cells in the thymus, and the main pathogenic mechanisms are believed to be T cell-mediated, but little is known about the role of B cells. Here, we give an overview of the role of B cells in thymic and peripheral tolerance in APS-1 patients and different AIRE-deficient mouse models. We also look closely into which autoantibodies have been described for this disorder, and their implications. Based on what is known about B cell therapy in other autoimmune disorders, we outline the potential of B cell therapies in APS-1 and highlight the unresolved research questions to be answered.

Highlights

Autoimmune polyendocrine syndrome type 1 (APS-1), known as autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), is a monogenetic autoimmune disease with an estimated prevalence of 1:100,000 caused by mutations in the autoimmune regulator (AIRE) gene [1,2,3,4,5]
AIRE is mainly expressed in a subset of thymic medullary epithelial cells, regulating the expression of 20% of the 20,000 unique tissue-restricted antigens (TRAs) to be presented to the developing T cells during negative selection [17,18,19,20,21]
The development of marginal zone B cell (MZB) lymphoma has further been linked to increased levels of B cell-activating factor of the TNF family (BAFF) produced by dendritic cells (DCs) in the periphery upon IFN-α stimulation, highlighting that AIRE regulates T cell-independent