Genetic and Immunological Features of Insulin-Dependent Diabetes Mellitus as a Clinical Manifestation of Type 1 Autoimmune Polyglandular Syndrome

Type 1 autoimmune polyglandular syndrome (APS1) is a rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE). The fundamental pathogenetic mechanism appears to be mediated by T cells since the translated Aire protein is involved in the transcriptional regulation of the expression of organ-specific antigens within the thymus. While a high prevalence of this monogenic disease is reported in Finland and Scandinavia (Norway), there are also clusters of similar patients in continental Italy and Sardinia, among Iranian Jews, and in other countries. Criteria for the diagnosis of the syndrome are the presence of at least 2 of the following disorders: chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Other endocrine or nonendocrine autoimmune conditions can be associated with it, including insulin-dependent diabetes mellitus (type 1 diabetes). Type 1 diabetes has been rarely reported in different series of patients affected by the syndrome and especially among Finnish patients. In this chapter we discuss the relevant studies that highlight the peculiar genetic and immunological features that in addition to the effect of AIRE gene mutations are responsible for the occurrence of type 1 diabetes within the APS1 population in different countries. (C) 2017 S. Karger AG, Basel