title: Evidence against the importance in the disease process of antibodies to bovine thyroid-stimulating hormone found in some patients with Graves' disease.
abstract: The antibody to TSH (TSH-Ab) found in some patients with Graves' disease may be either an antiidiotype (anti-id-Ab) to the TSH receptor antibody (TRAb) or the antigen (idiotype) for which the anti-id-Ab is in fact TRAb. Four groups have found antibodies to bovine TSH (bTSH-Ab) in Graves' disease patients in a TSH binding-inhibiting immunoglobulin (TBII) RRA that uses [125I]bTSH. In this assay serum samples containing bTSH-Ab give highly negative TBII values. The purpose of this study was to look for any clinical significance of potential idiotypic-antiidiotypic network regulation related to bTSH-Ab. Twenty-one (0.49%) of 4285 Graves' disease patients had TBII values less than the mean -4 SD of normal subjects. In all 21, bTSH-Ab was found by incubation of [125I]bTSH with the patient's serum, and significant inhibition of binding of bTSH-Ab to bTSH by human TSH was found in only 3 of these serum samples. We investigated next whether the binding site of the anti-TSH-Ab mimicked the TSH receptor-binding site. Binding of [125I]bTSH to bTSH-Ab-positive serum was not inhibited by bTSH-Ab-negative, thyroid-stimulating immunoglobulin-positive [(+)], and/or TBII(+) immunoglobulin G. In one patient with human TSH-Ab, TSH-Ab appeared and disappeared, and when TSH-Ab was negative, TBII was positive. Inhibition of [125I]bTSH binding to TSH-Ab by the same patient's serum when that patient was serum thyroid-stimulating immunoglobulin(+), TBII(+), and TSH-Ab-negative was sought but not found. Changes in serum TSH-Ab activity and disease activity were not correlated in this patient. In six untreated patients with Graves' hyperthyroidism with bTSH-Ab, the serum T3 and T4 concentrations and the time required to become euthyroid during antithyroid drug treatment were not significantly different from those in 52 such patients without bTSH-Ab. These data suggest that bTSH-Ab is not an anti-id-Ab to TRAb and that TSH-Ab does not directly modulate the activity of Graves' disease.
authors.affiliation: Ito Hospital, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Noh
authors.forename: N
authors.initials: N
authors.lastname: Hamada
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Oyanagi
authors.forename: N
authors.initials: N
authors.lastname: Ishikawa
authors.forename: N
authors.initials: N
authors.lastname: Momotani
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Morii
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001666:Binding Sites, Antibody; D002417:Cattle; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D013972:Thyrotropin / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D013972:Thyrotropin