In vivo stimulation of thyroid hormone release by rabbit antibodies with thyroid stimulating activity raised against the mutated receptor peptide TSH-R-HIS17.
The present study was designed to examine whether thyroid stimulating antibodies (TSAb) against the mutated or non-mutated peptide of human TSH receptor stimulates release of thyroid hormones in mice in vivo. We generated antibodies against mutated TSH receptor peptide TSH-R-HIS17 and non-mutated TSH receptor peptide TSH-R-ASP17 immunizing the peptides to rabbits. We isolated immunoglobulin G (IgG) from these antibodies and injected iv into male ddy mice. Control mice were injected iv with bTSH or TSAb-negative normal rabbit IgG. Serum T3 and T4 concentrations were elevated after the administration of bTSH in a dose-dependent manner. Serum T3 and T4 concentrations were significantly elevated after the injection of IgG from the rabbit antibodies with TSAb activity produced against TSH-R-HIS17. However serum T3 and T4 remained within normal levels after the injection of IgG from the rabbit antibodies without TSAb activity toward TSH-R-ASP17. The present data offer in vivo support of the IgG with TSAb activity interaction with the TSH receptor of the thyroid and raise the possibility that TSAb against mutated human TSH receptor peptide might be contributed to induce thyroid hyperfunction.
Hirooka
Y
Y
Fourth Department of Internal Medicine, Aichi Medical University, Japan.
Mitsuma
T
T
Nogimori
T
T
Ishizuki
Y
Y
Sakai
J
J
Naruse
M
M
Fukayama
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001323:Autoantibodies / Q000494:pharmacology; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology; D018828:Immunoglobulins, Thyroid-Stimulating; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011817:Rabbits; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000276:immunology*; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones