Analysis of TSH receptor antibodies by human TSH receptor mutant

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 04671459
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 内分泌・代謝学
• Research Institution: CHIBA UNIVERSITY
• Principal Investigator: TERANO Takashi CHIBA UNIVERSITY, 2nd Dpartment of Internal Medicine. assistant professor, 医学部・附属病院, 助手 (70237006)
• Co-Investigator(Kenkyū-buntansha): TAMURA Yasushi CHIBA UNIVERSITY, 2nd Dpartment of Internal Medicine. assistant professor, 医学部, 助教授 (90009671) ; TAHARA Kazuo CHIBA UNIVERSITY, 2nd Dpartment of Internal Medicine. assistant professor, 医学部・附属病院, 助手 (60241965)
• Project Period (FY): 1992 – 1993
• Keywords: TSH receptor antibody / human TSH receptor mutant / Graves' IgG / rat LH-CG receptor / epitope / Struma / Graves' ophthalmopathy / サイクリックAMP

Research Abstract

Thyroid stimulating antibodies (TSAbs) ate the main cause of hyperthyroidism and goitor of Graves' disease. Atudies using TSH receptor/rat lutropin-chonionic gonadotropin (LH-CG) receptor chimeras have shown that epitopes for TSAb in 94% Graves' patients exist within amino acid residues 90-165 on human TSH receptor extracellular domain, and those in 3% patients within residues 22-89, TSAb wpitopes for another 3% of Grves' patients do not exist within residues 22-165. thus, we are constracting new chimeric TSHreceptors which have LH-CG receptor sequences within residues 166-415 and investigating the epitopes for these particular type of TSAb.
This results indicate that Graves' TSAbs can be classified into at least three types, recgnizing defferent epitopes on human TSH receptor. Now, we are constracting new chimeric TSH recoptors, which have shorter segment (20 to40 aminoacids) LH-CG receptor sequence within residues 22-165 on human TSH critical determinants of receptor to identity TSAb epitopes. Study with a chimenic receptor which has LH-CG receptor sewuence within residues 260-370 clearly shows that non of all Graves' patients (more than 60 Graves' patients are sudied)has TSAb epitopes on this C-terminal region.
Correlation of clinical manifestations in Graves' patients with different types of TSAbs is also studied. There is no relationship of TSAb type with goiter, pretibial myxedema etc. except ophthalmopathy.
We find only two patients with TSAb epitope within residues 22-89, and these two patients have ophthalmopathy, It is not clear whether there is a correlation between this particular type of TSAb and ophthalmopaty, because only two patients are studied so far. More patients should be studied to clarity this question in future.