Delineating the autoimmune mechanisms in Graves’ disease

Abstract

The immunologic processes involved in autoimmune thyroid disease (AITD), particularly Graves’ disease (GD), are similar to other autoimmune diseases with the emphasis on the antibodies as the most unique aspect. These characteristics include a lymphocytic infiltrate at the target organs, the presence of antigen-reactive T and B cells and antibodies, and the establishment of animal models of GD by antibody transfer or immunization with antigen. Similar to other autoimmune diseases, risk factors for GD include the presence of multiple susceptibility genes, including certain HLA alleles, and the TSHR gene itself. In addition, a variety of known risk factors and precipitators have been characterized including the influence of sex and sex hormones, pregnancy, stress, infection, iodine and other potential environmental factors. The pathogenesis of GD is likely the result of a breakdown in the tolerance mechanisms, both at central and peripheral levels. Different subsets of T and B cells together with their regulatory populations play important roles in the propagation and maintenance of the disease process. Understanding different mechanistic in the complex system biology interplay will help to identify unique factors contributing to the AITD pathogenesis.

Iodine-131 therapy alters the immune/inflammatory responses in the thyroids of patients with Graves' disease

“…GD pathogenesis is generally characterized by abnormalities in T-cell subsets (2,3), innate immune cells (4), and various cytokines, which ultimately decreases immune tolerance and excessively activates B cells, promoting the production of thyroid stimulating hormone (TSH) receptor antibody (TRAb). The biased activation of helper T (Th) cells has an important role in GD development (5,6) and the imbalance of Th1/Th2 cell immunity may result in a shift toward the Th2-type immune response (7).…”

Polymorphism of IL37 gene as a protective factor for autoimmune thyroid disease

“…HT is a T cell-mediated organ-specific autoimmune disease characterized by lymphocytic infiltration that leads to thyroid cells loss, clinically manifested as hypothyroidism (Antonelli et al 2015). In contrast, GD is characterized by hyperthyroidism due to overproduction of thyroid hormone induced by specific auto-antibodies against thyrotropin receptor (TSHR) (Morshed et al 2012).…”

Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto’s disease

“…Therefore, IL-10 has been confirmed to play both immunoprotective and immunodestructive roles in diabetes [32]. Because the target tissues of HD and autoimmune diabetes have been shown to be destroyed by cytotoxic T cells [1][2][3], we hypothesized that local production of IL-10 may accelerate the cytotoxic activity of T cells in the thyroid glands of HD patients and that once thyroid-specific autoimmune destruction occurs, lower expression of let-7e may cause higher production of IL-10 and induce greater destruction of the thyroid glands in patients with severe HD.…”