Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease[1]

Abstract

Type 1 diabetes mellitus results from an immune mediated or idiopathic destruction of the pancreatic beta cells. Its aetiopathogenesis remains to be elucidated, despite great progress in the characterisation of beta-cell antigens, T-lymphocyte and antibody markers as well as whole genome screening. The incidence of type 1 diabetes is rising in most countries. Moreover, a considerable proportion of patients initially presenting with type 2 diabetes mellitus have an underlying type 1 diabetes with a latent course. A proportion of type 1 diabetes patients have concomittant thyroid autoimmune disease, either Hashimoto's thyroiditis or Graves' disease. Whereas Hashimoto's thyroiditis shares the same destructive immune process as type 1 diabetes, Graves' disease is unique in stimulating specifically the TSH-receptor through high-affinity immunoglobulins. However, both the thyroid autoimmune disorders and type 1 diabetes have susceptibility genes in common, implying shared pathways of immunopathogenesis. It has become clear that the genetic composition of a host at least partly determines the course of an immune response leading either to an organ-specific autoimmune disease or creating a state of balance where antibodies are hallmarks of (auto)immunity but normal function prevails. Genetic factors including MHC (IDDM 1-genetic locus) and non-MHC genes (IDDM 2 - IDDM X) have been shown to determine susceptibility to autoimmunity in type 1 diabetes or lifelong tolerance. Currently the importance of the various diabetes associated genes is becoming clearer due to functional studies. Our review attempts to compile the relevant data that have accumulated in recent years and offers perspectives for prediction, prevention and possibly even therapy of immune-mediated endocrinopathies.

Key words

Autoimmunity - HLA - immunogenetics - immunological synapse - type 1 diabetes

1 This review is decicated to Klaus H. Usadel on the occasion of his 65th birthday.

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1 This review is decicated to Klaus H. Usadel on the occasion of his 65th birthday.