Specific HLA alleles have a higher affinity to autoantigenic thyroidal peptides and can contribute to autoimmune thyroid disease development. Specifically, in Hashimotos disease, aberrant expression of HLA II on thyrocytes has been demonstrated. They can present thyroid autoantigens and initiate autoimmune thyroid disease. Susceptibility alleles are not consistent in Hashimotos disease. In Caucasians, various alleles are reported to be associated with the disease, including DR3, DR5 and DQ7. CTLA-4 genes
This gene is the second major immune-regulatory gene related to autoimmune thyroid disease. CTLA-4 gene polymorphisms may contribute to the reduced inhibition of T-cell proliferation and increase susceptibility to autoimmune response. CTLA-4 is a major thyroid autoantibody susceptibility gene. A linkage of the CTLA-4 region to the presence of thyroid autoantibodies was demonstrated by a whole-genome linkage analysis. CTLA-4 was confirmed as the main locus for thyroid autoantibodies. Protein tyrosine phosphatase nonreceptor-type 22 gene
PTPN22 is the most recently identified immune-regulatory gene associated with autoimmune thyroid disease. It is located on chromosome 1p13 and expressed in lymphocytes. It acts as a negative regulator of T-cell activation. Mutation in this gene is a risk factor for many autoimmune diseases. Weaker T-cell signaling may lead to impaired thymic deletion of autoreactive T cells, and increased PTPN22 function may result in inhibition of regulatory T cells, which protect against autoimmunity. Immune-related genes
IFN-γ promotes cell-mediated cytotoxicity against thyroid mutations causing increased production of IFN-γ were associated with the severity of hypothyroidism.
History
Also known as Hashimotos disease, Hashimotos thyroiditis is named after Japanese physician Hakaru Hashimoto (1881−1934) of the medical school at Kyushu University, who first described the symptoms of persons with struma lymphomatosa, an intense infiltration of lymphocytes within the thyroid, in 1912 in the German journal called Archiv für Klinische Chirurgie. This paper was made up of 30 pages and 5 illustrations all describing the histological changes in the thyroid tissue. Furthermore, all results in his first study were collected from four women. These results explained the pathological characteristics observed in these women especially the infiltration of lymphoid and plasma cells as well as the formation of lymphoid follicles with germinal centers, fibrosis, degenerated thyroid epithelial cells and leukocytes in the lumen. He described these traits to be histologically similar to those of Mikulics disease. Like mentioned above, once he discovered these traits in this new disease, he names the disease struma lymphomatosa. This disease emphasized the lymphoid cell infiltration and formation of the lymphoid follicles with germinal centers, neither of which had ever been previously reported.Despite Dr. Hashimotos discovery and publication, the disease was unfortunately not recognized as distinct from Reidels Thyroiditis which was a common disease at that time in Europe. Although many other articles were reported and published by other researchers, Hashimotos struma lymphomatosa was only recognized as an early phase of Reidels Thyroiditis in the early 1900s.