Patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), develop autoantibodies to multiple self-proteins. The patients have high titer autoantibodies to multiple cytokines, most prominently to type 1 interferons and cytokines associated with Th17 cell functions. In addition to these signature autoantibodies, APECED patients develop autoantibodies to many other self-proteins characteristic to autoimmune diseases and display broad autoantibody repertoires with high inter-individual variations. These autoantibodies have gone through somatic hypermutation during their affinity maturation, and the autoantibody targets are enriched for evolutionarily conserved phosphoproteins, including tumor-specific autoantigens. Interestingly, the target autoantigens are not limited to proteins expressed in thymic medullary epithelial cells, and in contrast, many are expressed in lymphoid type of cells. Our findings support the hypothesis that specific protein properties contribute to the etiology of B cell autoimmunity.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology