Thyroglobulin, thyroperoxidase, and thyrotropin-receptor autoantibodies

Thyroglobulin (Tg) plays an essential role in the storage of iodine and synthesis of iodinated thyroid hormones, thyroxine (T4) and triiodothyronine (T3). The main hormonogenic acceptor tyrosines are at positions 5, 1291, 2554, 2568, and 2747 of human Tg, while donor iodinated tyrosine sites are at positions 130, 847, and 1448. Normally, no more than 25% of the tyrosines are iodinated. The iodine content of Tg varies considerably with the diet of the individual. Evidence that dietary iodine plays a role in modulating autoimmune thyroiditis is based on clinical and epidemiological evidence and on experimental studies of thyroiditis-prone animals. Tg can be purified by ammonium sulfate precipitation of thyroidal extracts, followed by gel filtration chromatography using Sephacryl S-400. The large Tg molecule elutes right after the void volume. Tg antibodies are primarily IgG and distribute among the four IgG subclasses. IgG2 tends to predominate in Hashimoto's thyroiditis, whereas IgG4 is more represented in patients with Graves' disease, nontoxic goiter, and differentiated thyroid carcinoma. The subclass may reflect the type of T-helper cell population associated with the particular disease. Tg antibodies can be measured by indirect immunofluorescence, hemagglutination, radioimmunoassays, and enzyme-linked immunosorbent assay (ELISA). ELISA and hemagglutination are the two most commonly used procedures. Many assays for Tg autoantibody detection are FDA approved, although their results do not always agree. Patients, in fact, develop Tg autoantibodies that bind different epitopes, are in different subclasses, and have different affinities.