Antithyroid autoantibodies
Antithyroid autoantibodies (or simply antithyroid antibodies) are
Subtypes
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
TSH receptor antibodies
The thyrotropin receptor (TSH receptor) is the antigen for TSH receptor antibodies (TRAbs). It is a seven transmembrane G protein-coupled receptor that is involved in thyroid hormone signalling. TRAbs are grouped depending on their effects on receptor signalling; activating antibodies (associated with hyperthyroidism), blocking antibodies (associated with thyroiditis) and neutral antibodies (no effect on receptor). Activating and blocking antibodies mostly bind to conformational epitopes, whereas neutral antibodies bind to linear epitopes. Binding of the antibody to the amino terminus of the TSH receptor shows stimulatory activity, whereas binding to residues 261-370 or 388-403 block the activity. TRAbs are present in 70–100% of Graves' disease (85–100% for activating antibodies and 75–96% for blocking antibodies) and 1–2% of normal individuals.[1][2][11]
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.[2][13]
The clinical and physiological relevance of neutral antibodies remains unclear. However, they may be involved in prolonging the TSH receptor half-life.[2]
Thyroglobulin (TG) antibodies
Thyroglobulin antibodies are specific for thyroglobulin, a 660 kDa matrix protein involved in the process of thyroid hormone production. They are found in 70% of Hashimoto's thyroiditis, 60% of idiopathic hypothyroidism, 30% of Graves' disease, a small proportion of thyroid carcinoma and 3% of normal individuals.[1][3] 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.[14]
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.[1]
Pathogenesis
The production of antibodies in Graves' disease is thought to arise by activation of
While anti-thyroid antibodies are used to track the presence of autoimmune thyroiditis, they are generally not considered to contribute directly to the destruction of the thyroid.[10]
Effect on human reproduction
The presence of anti-thyroid antibodies is associated with an increased risk of
History
In 1912 Hakaru Hashimoto described hypothyroidism and goiter associated with thyroid lymphoid infiltration. In 1956 the anti-Tg antibody was detected in similar cases, elucidating the autoimmune cause of these characteristics. Later the same year, activating TSH receptor antibodies were discovered. Thyroid microsomal antibodies were discovered in 1964, which were subsequently renamed anti-TPO antibodies due to the identification of their autoantigen.[1]