1998 Fiscal Year Final Research Report Summary
Deveolpment of new laboratory examination for autoimmune thyroid desease
| Project/Area Number |
09672355
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SUGAWA Hideo Medicine, Laboratory Medicine, Kyoto University, lecturer, 医学研究科, 講師 (70162857)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUGI Shinji Medicine, Laboratory Medicine, Kyoto University, assistant, 医学研究科, 助手 (50252432)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Autoimmunity / Thyroid / Thyrotropin receptor / Autoantibody / Epitope spreading / ELISPOT / Diagnosis / helper T cell |
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| Research Abstract |
Monoclonal antibodies were established by immunizing mice with a synthetic peptide (P354-14) corresponding to "the immunogenic peptide" of human thyrotropin receptor (hTSH-R). Obtained antibodies showed various biological activities, and gave an evidence of B-cell epitope spreading. These antibodies were radiolabeled and used for binding assay to hTSH-R-expressed CHO cell. To this system, many sera from patients with Graves' disease showed inhibitory action. But the clinical features did not correlate with their inhibitory profiles. Simultaneously, the spleen cells were subjected to antigen-specific ELISPOT assay in co-culture with various synthetic peptides of THS-R.Used cytokines were Interferon gamma (IFN-gamma ) for Th1, and Interleukin 4 (IL-4) for Th2. Results indicated that immunization with C-terminal TSH-R-specific insert peptide causes fluctuation in the Th2 cell population but not Th1 cells in the autoimmune system against the TSH-R, and the recognition repertoire of Th2 was expanded by the peptide. This supported the results of former B-cell epitope spreading at the level of helper T cells. Then, we established stable antigen-specific assay system of ELISPOT to measure activated helper T cells at their subclass levels. We applied this assay to examine the activation of T cell from Graves' patients. Basal activity of Th2 cells and their responsibility to TSH-R were increased in Graves' patients than healthy controls. No difference of Th1 activity was observed in Graves' patients. In conclusion, antigen-specific ELISPOT assay using synthetic peptides corresponding to human TSH-R is very useful to diagnose and research for autoimmune thyroid disease (Graves' disease).
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Research Products
(32 results)
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[Publications] Shinji, Kosugi, Akira, Matsuda, Noritake, Hai, Norihiko, Aoki, Hideo, Sugawa, and Toru, Mori: "Aspartate-474 in the first exoplasmic loop of the thyrotropin receptor is crutial for receptor activation" FEBS letter. 406. 139-141 (1997)
Description
「研究成果報告書概要(和文)」より
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[Publications] Toru, Mori, Hideo, Sugawa, Shinji, Kosugi, Michiko, Ueda, Noritaka, Hai and Akira, Matsuda: "Recent trends in the management of Graves' hyperthyroidism in Japan : Opinion Survey results, especially on the combination of antithyroid drug and thyroid hormone." Endocrine Journal. 44. 509-517 (1997)
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「研究成果報告書概要(和文)」より
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[Publications] Toru, Mori, Hideo, Sugawa, Shinji, Kosugi, Michiko, Ueda, Daisuke, Inoue and Takashi, Akamizu: "Effectiveness of a short-term steroid treatment on the reduction in goiter size in antithyroid drug-treated patients with Graves' disease." Endocrine Journal. 44. 575-580 (1997)
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「研究成果報告書概要(和文)」より
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[Publications] 赤水, 尚史, Michele, Sale, Donald Bowden, Stepben, Rich, 奥田, 譲治, 須川, 秀夫, 吉村, 弘, 岩崎, 博幸, 伊藤, 國彦, 横田, 敏彦, 横, 俊清, 井上, 大輔, 渋谷, 雄平, 森, 徹, 中尾, 一和: "TSH受容体遺伝子マイクロサテライト多型と自己免疫性甲状腺疾患との関連" 日本内分泌学会雑誌. 73. 236 (1997)
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「研究成果報告書概要(和文)」より
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[Publications] Hideo, Sugawa, Yoshihiro, Ueda, Michiko, Ueda, Shinji, Kosugi, Satoshi, Ichiyama, and Toru, Mori: "Immunization with the ‘immunogenic peptide' of TSH receptor induces oligoclonal antibodies with various biological activities." Peptides. 19. 1303-1307 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Akio, Yoshida, Norihito, Sasaki, Atsusi,Mori, Shinichi, Taniguchi, Yoshihiro, Ueta, Kimihiko, Hattori, Yasunori, Tanaka, Osamu, Igawa, Mariko, Tsuboi, Hideo, Sugawa, Ryoichi, Sato, Ichiro, Hisatome, Chiaki, Shigemasa, Evelyn F., Grollman, Shinji, Kosugi: "Differences in the electrophysiological response to I^1 and the inhibitory anions SCN^- and CLO_4^-, studied in FRTL-5 cells." Biochimica et Biophysica Acta. 1414. 231-237 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Hideo, Sugawa, Michiko, Ueda, Akira, Matuda, Noritaka, Hai, Akio, Yoshida and Shinji, Kosugi: "Lack of measurable maximal capacity of inorganic iodide pool in non-thyroid cell." International Journal Thyroidology, Clinical and Experimental. in press. (1999)
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「研究成果報告書概要(和文)」より
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[Publications] 上田, 路子, 裴, 紀堯, 小杉, 眞司, 一山, 智, 森, 徹, 須川, 秀夫: "モノクローナル甲状腺刺激ホルモン受容体体抗体の臨床応用のための基礎検討(1)" 第41回日本臨床病理学会近畿支部総会抄録集. 82 (1998)
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「研究成果報告書概要(和文)」より
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[Publications] Akio Yoshida, Norihito Sasaki, Atsusi Mori, Shinichi Taniguchi, Yoshihiro Ueda, Kimihiko Hattori, Yasunori Tanaka, Osamu Igawa, Mariko Tsuboi, Hideo Sugawa, Ryoichi Sato, Ichiro Hisatome, Chiaki Shigemasa, Evelyn F.Grollman, Shinji Kosugi.: "Difference in the electrophysiological response to I and the inhibitory anions SCN and CLO_4, studied in FRTL-5 cells." Biochimica et Biophysica Acta. 1414. 231-237 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takashi Akamizu, Michele Sale, Donald Bowden, Stepben Rich, Jyouji Okuda, Hideo Sugawa, Hiroshi Yoshimura, Hiroyuki Iwasaki, Kunihiko Ito, Toshihiko Yokota, Shunsei Kou, Daisuke Inoue, Yuuhei Shibuya, Toru Mori, Kazuwa Nakao.: "Relationship between microsatelitte polymorphism of TSH receptor gene and autoimmune thyroid disease." Folia Endocrinologica Japonica. vol73. 236 (1997)
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