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慢性関節リウマチにおける自己抗体の産生と病因的意義の研究

Research Project

Project/Area Number 05454241
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionFukushima Medical University

Principal Investigator

粕川 禮司  福島県立医科大学, 医学部, 教授 (80045632)

Co-Investigator(Kenkyū-buntansha) 佐藤 由紀夫  福島県立医科大学, 医学部, 助手 (20254013)
宮田 昌之  福島県立医科大学, 医学部, 助手 (40219788)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsIgMリウマトイド因子 / アミノ酸配列 / 熱ショック蛋白65 / ヒト熱ショック蛋白60 / γδ^+T細胞 / 補体活性化 / 熱ショック蛋白 / gammadelta^+T細胞
Research Abstract

RA患者滑膜から得られたB細胞をEBウイルスでトランスホームし、IgM-RF産生クローンを得た。
IgG-FCとのみ反応するmonoreactive RFが、他のssDNAやコラゲンIIと反応するpolyreactiveRFより、より多く得られた。monoreactiveIgM-RFのIgGFC結合力はpolyreactiveIgM-RFより強く、C4結合能も高かった。RA滑膜B細胞クローンから得られたIgA-RF産生細胞のRNAから得られたVH域のcDNA解析でVHのgermline DD66と87%のhomologyが認められ、VHcDNAのCDR1と2域に体細胞突然変異が多く認められた。
RA患者滑液中にはマイコバクテリウムHSP65KDaに対するIgG,IgM,IgA抗体が血清中より、より高値で認められた。
RA患者滑液単核球には末血単核球よりマイコバクテリウムHSP65KDaに対して3Hサイミジン取り込みでみられるより強い反応が認められた。この反応性と単核球中のHLA-DR^+γδ^+T細胞比率との間に相関が認められたことから、γδ^+T細胞がHSP65に対して強い反応を示すことが推測された。
RA患者血清にはヒトHSP60と反応する抗体が証明され、RA滑膜から得られたcDNAのクローンから得られたヒトHSP60のエピトープは他種HSPとhomologyの高い部位のほかに、他のいくつかの部位にも存在することが認められた。RA患者血清は他の膠原病患者血清に比しいくつかのエピトープと反応することが多く、しかも、epitopeが経時的に拡散するのが認められた。

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 粕川禮司 他: "自己抗体の産生機序" nano GIGA. 2. 28-34 (1993)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyata M.& Kasukawa R.: "Rheumatoid factor:A review of the mode of formation and role in transplantation." Fukushima J Med Sci. 39. 15-28 (1993)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato Y.,Kasukawa R.et al: "Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors." Ann Rheum Dis. 52. 795-800 (1993)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Oda A.,Kasukawa R.et al: "Antibodies to 65kd heat shock protein were elevated in rheumatoid arthritis." Clin Rheumatol. 13. 261-264 (1994)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kogre A.,Kasukawa R.et al: "Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65KDa." J Rheumatol. 21. 1403-1408 (1994)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kokubun M.,Kasusawa R et al: "Multiple B cell epitopes on human heat shock protein 60,in the patients with rheumatoid arthritis" Arthritis rheum. 37. S313- (1994)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sato Y.,Kasukawa R.et al: "Sjogren′s Syndome(ed by M.Homma)Kugler Publications" Variable region gene analysis of IgA rheumatoid factor derived from a patient with Sjogren′s syndrome., 4 (1993)

    • Related Report
      1994 Final Research Report Summary
  • [Publications] 粕川 禮司 他: "自己抗体の産生機序" nano GIGA. 2. 28-34 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Miyata M.& Kasukawa R.: "Rheumatoid factor:A review of the mode of formation and role in transplantation." Fukushima J Med Sci. 39. 15-28 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato Y.,Kasukawa R.et al: "Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors." Ann Rheum D_<1S>. 52. 795-800 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Oda A.,Kasukawa R.et al: "Antibodies to 65kd heat shock protein were elevated in rheumatoid arthritis." Clin Rheumatol. 13. 261-264 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kogre A.,Kasukawa R.et al: "Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65KDa." J Rheumatol. 21. 1403-1408 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kokubun M.,Kasukawa R et al: "Multiple B cell epitopes on human heat shock protein 60,in the patients with rheumatoid arthritis" Arthritis rheum. 37. S313- (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato Y.,Kasukawa R.et al: "Sjogren's Syndome(ed by M.Homma)Kugler Publications" Variable region gene analysis of IgA rheumatoid factor derived from a patient with Sjogren's syndrome., 4 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sato Y.,Kasukawa R.,et al: "Complement activating properties of monoreactive and polyre-active IgM rheumatoid factor." Ann Rheum Dis. 52. 795 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato Y.,Kasukawa R.,et al: "Estimation of complement activating properties of IgM rheuma-toid factor reacted with IgG subclasses" J Rheumatol. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Oda A.,Kasukawa R.,et al: "Antibodies to 65Kd heat-shock protein were elevated in rheuma-toid arthritis" Clin Rheumatol. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kogure A.,Kasukawa R.,et al: "Proliferactive response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to Mycobacterial 65Kd heat shock protein and its association with HLA DR gammadelta T cells." J Rheumatol. (in press).

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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