[Topics on immunogenic regions in TSH receptors for thyroid disease]

Immunogenic regions in human TSH receptors responsible for autoimmune thyroid disease were studied using synthetic TSH receptor-related peptides. Eight different peptides corresponding to segments of the extracellular domain of TSH receptor were synthesized. Immunoglobulin G(IgG) of patients with Graves' disease bound to two of eight peptides, peptide # 1 (32-56) and peptide # 5(309-337). IgG of patients with Hashimoto's thyroiditis bound to a different region of TSH receptors, peptide #8 (333-359). One of three rabbit antisera against peptide #1 showed significant thyroid stimulating activity, although rabbit antisera against peptide #5 lacked the stimulating activity. An antiserum against peptide #1, but none of those one against peptide #5, recognized TSH receptor-like immunoreactivity in human peripheral blood. The molecular weight of the immunoreactivity was approximately 60kDa, on both high performance gel filtration chromatography and Western blot analysis. The amount of peptide #1 immunoreactivity was significantly higher in Graves' plasma than that in plasma of either normal or hypothyroid patients with Hashimoto's thyroiditis. These results indicate that the main immunogenic region for Graves' IgG exists near the N-terminal of human TSH receptors and TSH receptor-like immunoreactivity is present in human peripheral blood, which may contribute to the pathophysiology of Graves' disease.