Biological activity of anti‐thyrotropin anti‐idiotypic antibody

Abstract

Rabbit anti-rat anti-human thyrotropin anti-idiotypic antibodies have been raised. These antibodies were active at the thyrotropin (TSH) receptor, in that they inhibited 125I-labeled bovine TSH binding to thyroid plasma membranes, stimulated adenylate cyclase activity through a guanyl nucleotide-dependent mechanism, augmented radioiodide transport into isolated porcine thyroid follicular cells and induced such cultured cells to organize into follicles. Aside from substantiating the expectation that anti-hormone anti-idiotypic antibodies may possess properties of the original hormone, this work raised the possibility that thyroid-stimulating antibodies which cause the hyperthyroidism of Graves' disease may be anti-TSH anti-idiotypic antibodies.

Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

“…Recently, it has been shown that anti-id antibodies to anti-TSH antibodies have the capability of binding to the TSH receptor and causing stimulation (27). Similar studies have been performed using acetyl-choline (5), beta adrenergic (8), insulin (28), and F-met-leu-phe (29) receptors.…”

“…Similar studies have been performed using acetyl-choline (5), beta adrenergic (8), insulin (28), and F-met-leu-phe (29) receptors. Islam et al (27) have suggested than an antibody response to TSH may be the initiating event in Graves' disease, with the Rbabs being anti-id antibodies that develop in response to the anti-TSH (I 1). This is unlikely, in our view, for a number ofreasons.…”

Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

“…One of the sera obtained inhibited TSH binding to TM and had both inhibitory and stimulatory effects on thyroidal adenyl cyclase, depending on the experimental conditions (20). Current studies have demonstrated that an antiidiotype with thyroid-stimulating activity can arise as an autoantiidiotype in animals immunized with TSH.…”

“…Antiidiotypic antibodies to anti-TSH were previously obtained by Islam and co-workers who immunized rabbits with rat anti-TSH (20). One of the sera obtained inhibited TSH binding to TM and had both inhibitory and stimulatory effects on thyroidal adenyl cyclase, depending on the experimental conditions (20).…”

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“…Similarly, antithyrotropin antibodies induce antiidiotypic autoantibodies which bind to thyrotropin receptors on cells. These autoantibodies also express a CRI (32). It has further been shown that antireovirus antibodies provoke an anti-Id response directed against cellular reovirus receptors (33).…”