Infection, thyroid disease, and autoimmunity

The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basis for this review. Classical AITD (i.e. Graves' disease and Hashimoto's thyroiditis) has been shown to be associated with a variety of infectious agents (e.g. Yersinia enterocolitica, retroviruses) while infections of the thyroid gland (e.g. subacute thyroiditis, congenital rubella) have been shown to be associated with thyroid autoimmune phenomena. However, the causative role of infectious agents in AITD has not been definitively demonstrated in humans although AITD can be induced in experimental animals by certain viral infections. Infectious agents may induce thyroid autoimmunity by a variety of diverse mechanisms, such as inducing modifications of self-antigens, mimicking self-molecules, inducing polyclonal T cell activation (for example by superantigens), altering the idiotypic network, forming immune complexes, and inducing expression of MHC molecules on thyroid epithelial cells. While indirect data suggesting involvement of the infecting organisms in the pathogenesis of human AITD is abundant, only a limited number of studies have employed direct approaches. Such a direct approach would involve isolation or molecular identification of the potentially infecting organisms from the thyroid gland and the subsequent induction of AITD in an experimental model.