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Study on the pathogenesis of thyroid-associated ophthalmopathy

Research Project

Project/Area Number 10671048
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKURUME UNIVERSITY

Principal Investigator

HIROMATSU Yuji  Kurume University School of Medicine, Associate professor, 医学部, 助教授 (10201740)

Co-Investigator(Kenkyū-buntansha) SOYEJIMA Eri  Kurume University School of Medicine, Associate, 医学部, 助手 (20301666)
MIYAKE Ikuyo  Kurume University School of Medicine, Associate, 医学部, 助手 (50291828)
SATO Masayuki  Kurume University School of Medicine, Associate, 医学部, 助手 (90215848)
長沢 徳子  久留米大学, 医学部, 助手 (60261070)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsGraves' ophthalmopathy / Thyroid-associated ophthalmopathy / cytokine / T cell receptor Vβ gene usage
Research Abstract

lt is generally accepted that thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder, which is closely associated with Graves' disease. However, the nature of autoantigen and its pathological mechanisms has not been clear. In the present study we have attempted (1) to investigate cytokine profile of the enlarged eye muscle tissues and retrobulbar fat tissues from patients with TAO. (2) We also investigated T cell receptor Vβ gene usage in these 2 sites of the lesions whether T cells recognize the same autoantigen or not.
We have studied 14 eye muscle tissues and 29 orbital fat tissues from 33 patients with TAO. Cytokine gene expression was assessed by RT-PCR. Th1 and proinflammatory cytokines were predominantly detected in eye muscle tissues, while Th2 cytokines were predominantly detected in orbital fat tissues. Eye muscle enlargement, assessed by CT, was significantly correlated with TNFα gene expression in eye muscle. On the other hand, orbital fat volume was negatively correlated with IL-4 and IL-10 gene expression. These results suggest that both Th1 like and Th2 like immune reactions may play role in the development of two components of ophthalmopathy.
We have investigated the T cell clonality in 3 extraocular muscle tissues and 5 retrobulbar fat tissues from patients with TAO. T cell receptor Vβ gene usage was assessed by RT-PCR and SSCP methods. Several bands were detected in each Vβ gene, suggesting the existence of T cell clonality in these tissues. Furthermore, there were several distinct bands at the same mobility between eye muscle and orbital fat tissues. The present study suggest that both T cells reactive with the same autoantigen between 2 sites (eye muscle tissue and orbital fat tissue) and T cells reactive with the other antigens, are accumulating in those 2 sites in TAO. T cell immunity may be important in the development of ophthalmopathy.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] Yuji Hiromatsu, et al.: "Cytokine Profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy"J Clin Endocrinol Metab. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuji Hiroamtsu, Damu Yang, Tomasz Bednarczuk, Ikuyo Miuake, Kyohei Nonaka. Yoichi Inoue: "Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy."J Clin Endocrinol Metab. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuji Hiromatsu,et al.: "Cytokine Profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy."J Clin Endocrinol Metab. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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