Anti-thyroid antibodies can be subdivided into groups according to their target antigen.
Anti-TPO antibodies Anti-thyroid peroxidase (anti-TPO) antibodies are specific for the
autoantigen TPO, an
enzyme that catalyses iodine oxidation and thyroglobulin tyrosyl iodination reactions in the thyroid gland. Most antibodies produced are directed to
conformational epitopes of the
immunogenic carboxyl-terminal region of the TPO protein, although antibodies to
linear epitopes have been seen. Anti-TPO antibodies are the most common anti-thyroid autoantibody, present in approximately 90% of
Hashimoto's thyroiditis, 75% of Graves' disease and 10–20% of
nodular goiter or
thyroid carcinoma. Also, 10–15% of normal individuals can have high level anti-TPO antibody titres. High serum antibodies are found in active phase chronic autoimmune thyroiditis. Thus, an
antibody titer can be used to assess disease activity in patients that have developed such antibodies. The majority of anti-TPO antibodies are produced by thyroid infiltrating
lymphocytes, with minor contributions from lymph nodes and the bone marrow. They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity.
Activating TRAbs are characteristic of Graves' disease (autoimmune hyperthyroidism). TPO antibody is measured more easily than the TSH receptor antibody, and so is often used as a surrogate in the diagnosis of Graves' disease. These antibodies activate adenylate cyclase by binding to the TSH receptor. This causes the production of thyroid hormones and subsequent growth and vascularisation of the thyroid.
Blocking TRAbs (also known as thyrotropin binding inhibitory immunoglobulins (TBII)) competitively block the activity of TSH on the receptor. This can cause hypothyroidism by reducing the thyrotropic effects of TSH. They are found in Hashimoto's thyroiditis and Graves' disease and may be cause of fluctuation of thyroid function in the latter. During treatment of Graves' disease they may also become the predominant antibody, which can cause hypothyroidism. Anti-TPO antibodies are present in 99% of cases where thyroglobulin antibodies are present, however only 35% of anti-TPO antibody positive cases also demonstrate thyroglobulin antibodies.
Anti–Na+/ I− symporter Anti-Na+/I− symporter antibodies are a more recent discovery of possible thyroid autoantibodies and their role in thyroid disease remains uncertain. They are present in approximately 20% of Graves' disease and 24% of Hashimoto's thyroiditis. ==Pathogenesis==