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1995 Fiscal Year Final Research Report Summary

Analysis of pathogenesis of autoimmune thyroid disease

Research Project

Project/Area Number 06454341
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionNagasaki University

Principal Investigator

NAGATAKI Shigenobu  Nagasaki University, School of Medicine, Professor, 医学部, 教授 (70010311)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Naokata  Nagasaki University, School of Medicine, Assistnt, 医学部, 助手 (10240219)
Project Period (FY) 1994 – 1995
KeywordsAutoimmune thyroid diseas / Thyrotropin (TSH) receptor / TSH receptor antibody / Fusion protein
Research Abstract

Both humonal and cellular immunity play an important role in the pathogenesis of autoimmune thyroid disease (AITD). It remains, however, to be elucidated whether the thyrotropin receptor (TSHR) protein is involved in pathogenesis of AITD through cellular immunity. In the present disease, we expressed the extracellular domain of TSHR as a fusion protein with maltose-binding protein (TSHR-MBP) in bacteria and examined its abilities to induce functionally relevant anti-TSHR antibodies and experimental autoimmune thyroiditis in four different H-2 strains of mice and also to interact with TSH and Graves'sera. TSHR-MBP fusion protein was expressed in a soluble form and purified with an amylose resin column and gel extraction. Immunization with purified TSHR-MBP as well as purified MBP fused to a short sequence of beta-galactosidase elicited a good serum antibody-response to these proteins, but not functionally relevant anti-TSHR antibodies or experimental thyroiditis, in all strains of mice examined. Nevertheless, the significant decrease in serum concentrations of thyroxine was observed in majority of mice immunized with either TSHR-MBP or MBP-beta gal, suggesting a non-specific effect of immunization. Finally, neither TSH or Graves' sera could bind to MBP-TSHR specifically. These data, although some are contradictory to previous reports, suggest that the TSHR extracellular domain may not play a significant role in cellular immunity for the pathogenesis of AITD at least in an animal model, and further reinforce our previous conclusion that TSH and anti-TSHR autoantibodies in patients with AITD interact with conformationally intact TSHR.

  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kaoru Fuijiyama: "Suppressive doses of thyroxine do not accelerate age-related bone loss in late postmenopausal women." Thyroid. 5. 13-17 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaoru Fijiyama: "Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism." J Chin Endocr Metab. 80. 2135-2138 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Thyrotropin binding specificity for the thyrotropin receptor." J Endocrinol Invest. 18. 283-287 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takeshita: "Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan." J Chin Endocr Metab. 8. 2607-2611 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maria C.Villadolid: "Untreated Graves' disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance." J Clin Endocr Metab. 80. 2830-2833 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Ito: "Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology." Thyroid. 5. 365-368 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhide Tsuda: "Automated measurement of urinary iodine with use of ultraviolet irradiation." Clinical Chemistry. 41. 581-585 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "High affinity binding of thyrotropin(TSH)and thyroid-stimulating autoantibody for the TSH receptor extracellular domain." Thyroid. 4. 155-159 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akira Takeshita: "Sequence analysis of the thyrotropin (TSH) receptor gene in congenital primary hypothyroidism associated with TSH unresponsiveness." Thyroid. 4. 255-259 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells." Endocrinology. 135. 1060-1065 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuji Nagayama: "Exacerbation of thyroid autoimmunity by interferon α treatment in patients with chronic viral hepatitis : our studies and review of the literature." Endocrine Journal. 41. 565-572 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaoru Fujiyama: "Suppressive doses of thyroxine do not accelerate age-related bone loss in late postmenopausal women." Thyroid. 5. 13-17 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaoru Fujiyama: "Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism." J Clin Endocr Metab. 80. 2135-2138 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nagayama: "Thyrotropin binding specificity for the thyrotropin receptor." J Endocrinol Invest. 18. 283-287 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Takeshita: "Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan." J Clin Endocr Metab. 8. 2607-2611 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maria C.Villadolid: "Untreated Graves'disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM) enlargement by magnetic resonance." J Clin Endocr Metab. 80. 2830-2833 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masahiro Ito: "Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology." Thyroid. 5. 365-368 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhide Tsuda: "Automated measurement of urinary iodine with use of ultraviolet irradiation." Clinical Chemistry. 41. 581-585 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nagayama: "High affinity binding of thyrotropin (TSH) and thyroid-stimulating autoantibody for the TSH receptor extracellular domain." Thyroid. 4. 155-159 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akira Takeshita: "Sequence analysis of the thyrotropin (TSH) receptor gene in congenital primary hypothyrodism associated with TSH unresponsiveness." Thyroid. 4. 255-259 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nagayamai: "Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells." Endocrinology. 135. 1060-1065 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuji Nagayama: "Exacerbation of thyroid autoimmunity by interferon alpha treatment in patients with chronic viral hepatitis : our studies and review of the literature." Endocrine Journal. 41. 565-572 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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