Autoantibodies to the human thyrotropin receptor are not species specific.
To ascertain the clinical usefulness of nonhuman thyroid-dependent TSH radioligand-receptor assays, we have reexamined the species specificity of the human TSH receptor-binding site and the unique TSH binding-inhibiting activity (TBI) found in sera from patients with Graves' disease. The human TSH receptor had a high affinity for nonprimate TSH (0.7 + 0.1 x 10(10) M(-1). However, porcine TSH receptors were of higher affinity and ovine TSH receptors were of lower affinity than the human binding site. A human TSH preparation had a similar potency against bovine TSH standard (NIH-B8) when assessed in both human and porcine radioligand-receptor assays (10 + 1.4 U/mg), suggesting that human TSH receptors showed no evidence of species preference. Although immunoglobulins from normal sera had enhanced nonspecific binding to human rather than porcine or ovine thyroid, the interaction of Graves'-specific immunoglobulin was most dependent on the affinity of the TSH receptor for TSH rather than the species from which the thyroid was derived. Hence, of 10 individual globulin fractions chosen to span the range of TBI obtained with human TSH receptor system, there was complete agreement between human and porcine TBI indices. In contrast, 5 preparations became TBI negative using ovine thyroid. These negative globulin fractions were the lowest 5 titers examined, suggesting that titer was the important factor rather than receptor species. Neither the human TSH receptor-binding site nor the TBI activity found in sera from patients with Graves' disease demonstrated true species specificity. Hence, porcine thyroid may be substituted for human tissue in clinically applicable TBI assays.
D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D002417:Cattle; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology*; D011989:Receptors, Thyrotropin; D013045:Species Specificity; D013552:Swine; D013961:Thyroid Gland / Q000276:immunology; D013972:Thyrotropin / Q000378:metabolism
D001323:Autoantibodies; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin; D013972:Thyrotropin