Thyroid Autoantibodies: Thyroid Peroxidase and Thyroglobulin Antibodies

Graves disease (GD) and Hashimoto thyroiditis (HT) are two autoimmune disorders that commonly affect the thyroid gland. Thyroid peroxidase (TPO) and thyroglobulin (Tg) are two key thyroid antigens targeted by the immune system in autoimmune thyroid disease (AITD). The TPO antibodies are found in the majority of GD and HT patients and were recently found to react with two immunodominant epitopes located on the overlapping A and B domains. TPO antibodies recognize mostly conformational epitopes that depend on the structure and folding of the protein. Tg antibodies are less sensitive and specific than TPO antibodies in GD and HT. However, the Tg gene is one of the major autoimmune thyroid disease (AITD) susceptibility genes and is believed to be the key antigen-triggering AITD. Tg antigenicity may be influenced by post-translational modifications. It has been suggested that epitope spreading from Tg to TPO may occur in AITD, with Tg being the primary antigen responsible for breaking T- and B-cell tolerance and TPO being responsible for the maintenance of autoimmunity in AITD.