The role-playing autoantibodies in autoimmune thyroid diseases and their extra-thyroidal manifestations: review article

The presence of the antibodies against the main thyroid antigens, which include thyroid peroxidase (TPO) or microsomal antigen, thyroglobulin (Tg) as well as thyrotropin receptor or Thyroid Stimulating Hormone Receptor (TSH-R), is a hallmark and symbol of the autoimmune thyroid diseases (AITDs) as one of the most common autoimmune diseases (AD) around the world. The prevalence of the thyroid peroxidase antibodies (anti-TPO antibody) and the thyroglobulin antibodies (anti-Tg antibody) is considerably higher in patients suffering from Graves’ disease (GD) and Hashimoto's thyroiditis (HT, chronic autoimmune thyroiditis, autoimmune hypothyroidism). While the TSH receptor antibodies (TRAbs) are common in the patients suffering from GD, they are relatively rare and infrequent in HT patients. This fact may indicate that TRAbs are more specific than other antibodies. In fact, TRAbs as one of the most important autoantibodies against the different thyroid antigens, are a set of the heterogeneous group of antibodies that based on the function, fall into three categories, including TSHR-stimulating antibodies (TSAbs), TSHR-blocking antibodies (TBAbs), and the neutral antibodies (no effect on receptor). TSAbs and TBAbs result in overproduction and reduction of intracellular cAMP respectively. Therefore the induction of the relevant signaling pathways can be the cause of different clinical symptoms in the form of hyperthyroidism or hypothyroidism consecutively. The extra-thyroidal effects of TRAbs as the extra-thyroid GD manifestations, such as ophthalmopathy and dermopathy, often have an effect on the eyes as well as the skin with the relatively well-known immunological mechanisms of the antibodies functions. Hashimoto encephalopathy is an extra-thyroidal effects of anti-TPO that provokes the central nervous system. On the other hand, anti-TPO like anti-Tg can affect the reproductive organs of women and lead to infertility by an unknown mechanism. Moreover, the circulating antibodies against the thyroid antigens can also be detected in other autoimmune diseases such as rheumatoid arthritis (RA), type I diabetes (T1DM) and celiac disease (CD). In this review article, the most important types of thyroid autoantibodies, their essential immunological processes in AITD as well as the main and important clinical extra-thyroidal manifestations of them have been discussed and reviewed.