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The role of rheumatoid factor on altered immune responses of intra-articular lymhocytes in rheumatoid arthritis.

Research Project

Project/Area Number 01570354
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionUniversity of Tokyo

Principal Investigator

INOUE Tetsufumi  University of Tokyo, Department of Medicine, Associate Professor, 医学部(病)物療内科, 講師 (30092141)

Co-Investigator(Kenkyū-buntansha) SAWADA Tetsuji  University of Tokyo, Dep. of Medicine, Assistant Professor, 医学部(病)物療内科, 助手 (50235470)
HIROHATA Shunsei  University of Tokyo, Dep. of Medicine, Assistant Professor, 医学部(病)物療内科, 助手 (90189895)
木佐木 友成  東京大学, 医学部物療内科, 助手 (20169840)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsrheumatoid arthritis / interleukin 6 / rheumatoid factor / Fc receptor / hepatitis C virus / リウマチ因子 / FCレセプタ- / 単球
Research Abstract

Synovial fluids(SF)and sera(S)from patients witn rheumatoid arthritis(RA)were examined for IgM, IgM-rheumatoid factor(IgM-RF). albumin in and interleukin-6(IL-6)activity. The quotient of SFIS IGN-RF was elevated compared with that of SF/S albumin in 7 patients with seropositiye RA, although the quotient of SF/S IgN was low er than that of SF/S albumin. SF IL-6 activity was much higher than serum IL-6 activity in all the 7 RA patients. In synovial fluids from 22 seropositiye RA patients, SF IL-6 activity was significantly correlated with the SF I gill-RF. IGG-RF and IGA-RF, but not with SF[gM, [gG or IgA. Moreover, SF IGM-RF as well as SF IL-6 activity was significantly correlated with the Westergren erythrocyte sedimentation rate(ESR)or the Lansbury articular index. These results indicate that(L-6and RF might be Produced within the rheumatoid joints as a result of abnormal im mune system activation, which is associated with the disease activity of RA. Three of the 4 seronegative RA pat … More ients, however, showed high SF IL-6 without detectable levels of SF IGM-RF. indicating that IL-6 alone is not sufficient for IGM-RF production.
The expression of CD14, Fc gamma receptor l(FcgammaRI), FcrRH, and HLA-DR on peripheral blood monocutes from 9 atients with rheumatoid arthritis(RA)was studied to investigate their natures and their roles i. 1 the pathogenes is of rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients with active RA, 8 patien ts with RA in complete remission, and 14 healthy individuals, were stained with various monoclonal antibodies and analyzed on fluourescence activated cell sorter. The expression of CD14 as well as FcgammaRI and FcgammaRII was upregu lated on peripheral blood monocutes from active RA patients, although the expression of HLA-DR was not increased. In addition, the expression of FcgammaRI and FcRII on monocutes was still upregulated in RA patients in complete remi ssion, whereas the expression of CD14 on sonocytes was normalized in these patients. These results indicate that Peripheral blood sonocytes in active RA patients are already activated to express higher densities of CD14. In ad dition, our observation that C014 density was increased on a subset of circulating blood monocutes in active RA, that HLA-DR was not significantly altered and that FcgammaRI and FcgammaRIl were increased in both active and inactive RA is not compatible with the expected actions of IFN-gamma. Finally, it is suggested that peripheral blood monocut es in RA patients may have intrinsic abnormalities as evidenced by the enhanced expression of FcgammaRs, which is pe rsistently observed irrespective of the disease activity of RA. The development of rheumatoid arthritis(RA)has been considered to involve both genetic and environmental f actors. We describe a patient who developed Progressive RA after transfusion-associated hepatitis C virus infect ion. Of interest, our patient possessed the combination of HLA-DR4 and HLA-Bw54, which has been frequently observe d in Japanese patients with RA, indicating that he was genetically susceptible to the disease. This suggests that hepatitis C virus may trigger the development of RA in genetically susceptible individuals. It should of course be pointed out that RA could have been a chance occurrence in our patient. Patients with RA and hepatitis C virus infection should be studied prospectively to seek evidence in the joint fluid, joint tissue, or elsewhere, to distinguish whether the RA is triggered by hepatitis C infection or whether hepatitis C virus itself resides in th e joint, causing either an immune complex reaction or direct cytotoxicity. Less

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Hiroshi Oka,Shunsei Hirohata,Tetsufumi Inoue,Sachiko Iwamoto,Terumasa Miyamoto: "Quantitative determination of IgM-rheumatoi factor by enzyme immunoassay Standardization using a serum from rheumatoid arthritis patient." CLINICA CHIMICA ACTA. 188. 147-160 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shunsei Hirohara,Tetsufumi Inoue,Terumasa Miyamoto: "T cell regulation of in vitro IgM-rheumatoid factor production by normal human B cells:Differential effects of stimulation with immobilized monoclonal antibodies to CD3 and Staphylococcus aureus." Japanese Journal of Allergology. 39. 82-89 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shunsei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "Frequency analysis of human peripheral blood B cells producing IgM-rheumatoid factor." Journal of Immunology. 145. 1681-1686 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tetsuji Sawada,Shunsei Hirohata,Tetsufumi Inoue: "Correlation between rheumatoid factor and IL6 activity in synovial flaids from patients with rhematoid arthritis." Clinical and Experimental Rhaumatology. 9. 363-368 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tetsuji Sawada,Shunsei Hirohara,Tetsufmi Inoue: "Development of rheumatoid arthritis after hepatitis C virus infection : Report of a case." Arthitis and Rheumatism. 34. 1620-1621 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satoshi Shinohara,Shunsei Hirohata, Tetsufumi Inoue: "Pherotypic analysis of peripheral blood monocytes isolated from patients with rheumatoid arthritis." Journal of Rheumatology. 19. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] OKA, H., HIROHATA, S., INOUE, T.: "Quantitative determination of IgM-rheumatoid factor by enzyme immunoassay -standardization using a serum from rheumatoid arthritis patient." Clinic : Chemica Acta. 188. 147-160 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] HIROHATA, S., INOUE, T., MIYAMOTO, T.: "T cell regulation of in vitro IgM-rheumatoid factor production by normal human b cells-differential effects of stimulation with immobilized monoclonal antibodies to CD3 and staphylococcus aureus-." Allergy. 39. 82-89 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] HIROTA, S., INOUE, T., MIYAMOTO, T.: "Frequency analysis of human periheral blood B cells producing IgM-rheumatoid factor-differential effects of stimulation with monoclonal antibodies to CD3 and staphylococcus aureus-." J. Immunol. 145. 1681-1686 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] SAWADA, T., HIROTA, S., INOUE, T., ITO, K.: "Correlation Between rheumatoid factor and IL6 activity in synovial fluids from patients with rheumatoid arthritis." Clin. Exp. Rheumatol.9. 363-368 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] SAWADA, T. . HIROHATA, S., INOUE, T., ITO, K.: "Development of rheumatoid arthritis after hepatitis C virus infection : report of a case." Arthritis Rheum.34. 1620-1621 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] SHINOHARA, S., HIROHATA, S., INOUE, T., ITO, K: "Phenotypic analysis of peripheral blood monocytes isolated from patients with rheumatoid arthritis." J. Rheumatol. 19. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Oka,Shunsei Hirohata,Tetsufumi Inoue,Sachiko Iwamoto,Terumasa Miyamoto: "Quantitative determination of IgMーrheumatoid factor by enzyme immunoassay Stanolardization using a serum from rheumatoid arthritis patient." CLINCA CHIMICA ACTA. 188. 147-160 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shunsei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "T cell regulation of in vitro IgMーrheumatoid factor production by normal human B cells:Differential effects of stimulation with immobilized monodonal antibodies to CD3 and Staphylococcus acueus." Japanese Journal of Allergology. 39. 82-89 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shunsei Hirohata,Tetsufmi Inoue,Terumasa Miyamoto: "Frequency analysis of human peripheral blood B cells producing IgMーrheumatoid factor." Journal of Immunology. 145. 1681-1686 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tetsuji Sawada,Shunsei Hirohata,Tetsufumi Inoue: "Correlation between rheumatoid factor and IL6 activity in synoriol fluids from patients with rheumatoid arthritis." Clinical and Experimental Rheumatology. 9. 363-368 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tetsuji Sawada,Shunsei Hirohata,Tetsufumi Inoue: "Development of rheumatoid arthritis after hepatitis C virus infection:Report of a case." Arthritis and Rheumatism. 34. 1620-1621 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Satoshi Shinohara,Shunsei Hirohata,Tetsufumi Inoue: "Phenotypic analysis of peripheral blood inonocytes isolated from patients with rheumatoid arthritis" Journal of Rheumatology. 19. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Oka,Shuusei Hirohata,Tetsufumi Inoue,Sachiko Iwamoto,Terumasa Miyamoto: "Quantitative determination of IgMーrheumatoid factor by euzyme immunoassay standardization using a serum from rheumatoid arthritis patient." CLINICA CHIMICA ACTA. 188. 147-160 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shuusei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "T cell regulation of in vitro IgMーrheumatoid factor production by normal human B cells:Differenitial effects of stimulation with immobilized monoclonal antibodies to CD3 and staphylococcus aureus." Japanese Journal of Allergology. 39. 82-89 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shunsei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "Frequency analysis of human peripheral blood B cells producing IgMーrheumatoid factor" J Immunology. 145. 1681-1686 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Tetsuji Sawada,Shunsei Hirohata,Tetsufumi Inoue: "Correlation between rheumatoid factor and IL6 activity in synovial fluids from patients with rheumatoid arthritis." Clinical and Experimental Rheumatology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroshi Oka,Shunsei Hirohata,Tetsufumi Inoue,Sachiko Iwamoto,Terumasa Miyamoto: "Quantitative determination of IgM-rheumatoid factor by enzyme immunoassay.Standardization using a serum from rheumatoid arthritis patient." CLINICA CHIMICA ACTA.

    • Related Report
      1989 Annual Research Report
  • [Publications] Shunsei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "Tcell regulation of in vitro IgM-rheumatoid factor production by normal human B cells:Differential effects of stimulation with immobilized monoclonal antibodies to CD3 and Staphylococcus aureus" Japanese Journal of Allergology.

    • Related Report
      1989 Annual Research Report
  • [Publications] Shunsei Hirohata,Tetsufumi Inoue,Terumasa Miyamoto: "Frequency analysis of human peripheral blood B cells producing IgM-rheumatoid factor." J Immunol.

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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