Autoantibodies to the Human Thyrotropin Receptor Are Not Species Specific

Abstract

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.

Properties of thyrotropin (TSH) binding to plasma membranes prepared from rat fat tissues.

“…A significant correlation between the inhibition activities of Graves' IgG on TSH binding to guinea pig fat and human or porcine thyroid membranes was reported (Kishihara et al 1979b;Parkes et al 1985). From these findings it is conceivable that TRAb is not species specific as reported by Davies (1981) and Strakosch et al (1982).…”

Inhibition of TSH binding to chicken thyroid by some cases of LATS(long acting thyroid stimulator).

“…Davies (1981) has reported that antibodies to TSH receptor did not show any species specificity based on the results using human, porcine or ovine receptors. Also Strakosch et al (1982) examined TSH receptor assay using human, guinea pig, calf, pig and dog thyroid receptors.…”

“…TSH receptor antibody (TRAb) assay is done by measuring the displacement of labelled TSH from receptor (Smith&Hall 1981). TRAb assay has been reported using TSH receptor of mammalian thyroid or fat tissue (Petersen et al, 1977;Shewring& mith 1982;Strakosch et al, 1982;Humphries et al, 1982;Manley et al, 1974;Kishihara et al, 1979;1981), but there are no reports about TRAb assay using non-mammalian TSH receptor. It is felt that LATS stimulates the mammalian thyroid, but not the non-mammalian thyroid (Lepp&Oliner 1967;Ochi&De-Groot 1970).…”

“…For the determination of TRAb usually mammalian species such as human (Petersen et al Endocrinol. Japon. June 1986June et al, 1977, porcine (Shewring&Smith 1982;Strakosch et al, 1982), bovine (Humphries et al, 1982) and guinea pig thyroid (Manley et al, 1974), or guinea pig fat cell membrane (Kishihara et al, 1979;1981) are used. However, there are no reports of TRAb determination using nonmammalian thyroid.…”

Immunological similarity of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) with animal IgG

“…Zoological specificity of LATS and TSAb has been reported [19,20]. Available reports showed that LATS (TSAb) has high binding to TSH receptor of porcine and bovine thyroid compared to human.…”