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Analysis of a novel RNA epitope recognized by sera in patients with rheumatic diseases using randomized RNA epitope library

Research Project

Project/Area Number 10670427
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionJuntendo University

Principal Investigator

TAKASAKI Yoshinari  Juntendo University, Rheumatology, Associate Professor, 医学部, 助教授 (80154772)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Ken  Juntendo University, Rheumatology, Assistant Professor, 医学部, 講師 (20281355)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
KeywordsRNA / autoantibody / randomized RNA library / epitope / rheumatic disease / 自己免疫
Research Abstract

We defined a novel RNA epitope recognized by serum from a patient with Sjogren's syndrome (SjS) from a randomized RNA epitope library, and investigated the epitope reactivity of the anti-RNA antibodies in patients with various connective tissue diseases. Serum from SjS patient TS was used to select ligands from the library of RNA oligomers with a central region of 25 degenerate nucleotides. Bound RNA was recovered by reverse transcription, PCR amplification and subcloning. Sera from 32 of 61 patients with SS (52.4%) precipitated with one of the selected RNA (TS1・RNA ; CGAAAGUCCGAUCGGCGUAAUGCA), whereas sera from 8 of 41 patients with systemic lupus erythematosus (19.5%) and 3 of 25 patients with rheumatoid arthritis (12.0%) precipitated. Frequency of anti-SS-A antibodies was significantly higher in anti-TS1・RNA positive patients but there was no cross-reactivity between anti-SS-A and anti-TS1・RNA.The epitopes on this RNA were further analyzed by immunoprecipitation using mutants of TS1・RNA.The reaction of patient sera with the RNAs declined when any part of the TS1・RNA was mutated. This finding indicates that the selected TS1・RNA is a novel sequence-specific RNA epitope that binds specifically sera with MCTD and SjS.Then we attempted to study the clinical significance of antibodies to TS1・RNA.Whereas there was no significant correlation between anti-TS1・RNA and clinical features in SjS patients, anti-TS1・RNA antibodies significantly correlated with the laboratory findings such as anti-dsDNA, Sm and U1 RNP, and low serum level of complement in MCTD patients. In addition, the activities of renal involvement was significantly correlated with the titer of anti-TS1・RNA.
These results suggested that anti-TS1・RNA antibody is a novel antibody against the sequence specific RNA in SiS and MCTD patients and may play certain roles associated with autoantibody-production and pathogenesis in MCTD.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Abe K,Takasaki Y,Ushiyama C,Asakawa J,Fukazawa T,Seki M,Hirashima M,Ogaki M,: "Expression of CD8O and CD86 on peripheral blood T lymphocytes in patients with systemic lupus erythematosus."J Clin Immunol. 9. 58-66 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shiroki K,Isoyama T,Kuge S,Ishii T,Ohmi S,Hata S,Suzuki K,Takasaki Y,Nomoto A: "Intracellular redistribution of truncutated La protein produced by Poiovirus 3Cpro-mediated cleavage."J Virol. 73. 2193-2200 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takasaki Y,Abe K,Tokano Y,Hashimoto H: "The expression of LFA-1, ICAM-1, CD80 and CD86 molecules in lupus patiens : Implication for immunotherapy."Intern Med. 38. 175-177 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Isoyama T,Kamoshita N,Yasui K,Iwai A,Shiroki K,Toyada H,Yamada A,Takasaki Y,Nomoto A: "Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than on poliovirus RNA"J Gen Virol. 80. 2319-2327 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogasawara H,Kaneko H,Hishikawa T,Sekigawa I,Takasaki Y,Hashimoto H,Hirose S,Kaneko H,: "Molecular mimicry between human endogenous rerrovirus clone 4-1 and HLA class Iantigen : with reference to the pathogenesis of systemic lupus"Rheumatology. 38. 1113-1164 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takasaki Y,Kogure T,Takeuchi K,Kaneda K,Yano T,Hirokawa K,Hirose S,Shirai T,Hashimoto H,: "Reactivity of anti-proliferating cell nuclear antigen(PCNA)murine monoclonal antibodies to the PCNA multiprotein complexes involved in cell proliferation"J Immunol. 166(In press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高崎芳成,官川 薫,竹内 健,金田和彦,池田圭吾:橋本博史: "MCTDおよび各種膠原病におけるエピトープの解析(厚生省特定疾患対策研究事業混合性結合組織病に関する研究班平成11年度研究報告書)"厚生省特定疾患対策研究事業混合性結合組織病に関する研究班. 53-55(74) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shiroki K, Isoyama T, Kuge S, Ishii T, Ohmi S, Hata S, Suzuki K, Takasaki Y, Nomoto A: "Intracellular redistribution of trunctuated La protein produced by Poiovirus 3Cpromediated cleavage."J Virol. 73. 2193-2200 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Isoyama T, Kamoshita N, Yasui K, Iwai A, Shiroki K, Toyoda H, Yamada A, Takasaki Y, Nomoto A: "Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than on poliovirus RNA."J Gen Virol. 80. 2319-2327 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takasaki Y, Kogure T, Takeuchi K, Kaneda K, Yano T, Hirokawa K, Hirose S, Shirai T, Hashimoto H: "Reactivity of anti-proliferating cell nuclear antigen (PCNA) murine monoclonal antibodies to the PCNA multiprotein complexes involved in cell proliferation."J Immunol. 166 (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Amano H,Morimoto S,Kaneko H,Tokano Y,Takasaki Y,Hashimoto H: "Effect of intravenous cyclophosphamide in systemic lupus erythematosus : relation to lymphocyte subsets and activation markers"Lupus. 9. 26-32 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takasaki Y,Kaneda K,Takeuchi K,Yano T,Hashimoto H: "Antibodies to PCNA and K1-A linked set of autoimmune response associated with celluar function of target antigens"AAA. 1. 88-109 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高崎芳成,村上明弘,小島和夫,矢野哲朗,宮川薫,金田和彦,川口里江子,竹内健,橋本博史: "MESACUP-2 RNPによる抗U1 RNP抗体の測定-MESACUP RNP IIとの比較検討"医学と薬学. 44. 599-609

    • Related Report
      2000 Annual Research Report
  • [Publications] 高崎芳成,宮川薫,竹内健,金田和彦,池田圭吾,橋本博史: "MCTDおよび各種膠原病におけるエピトープの解析(厚生省特定疾患対策研究事業混合性結合組織病に関する研究班平成11年度研究報告書)"厚生省特定疾患対策研究事業混合性結合組織病に関する研究班. 53-55(74) (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takasaki Y, Abe Tokano Y, Hashimoto H: "The expression of LFA-1, ICAM-1, CD80 and CD86 molecules in lupus patiens: Implication for immunotherapy."Intern Med. 38. 175-177 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Abe K, Takasaki Y, Ushiyama C, Asakawa, J, Fukazawa T, et al: "Expression of CD80 and CD86 on peripheral blood Tlymphocytes in patients with systemic lupus erythematosus."J Clin Immunol. 19. 58-66 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shiroki K, Isoyama T, Kuge S, Ishii T, Ohmi S, Hata S, Takasaki Y, et al: "Intracellular redistribution of trunctuated La protein produced by Poiovirus 3Cpro-mediated cleavage."J Virol. 73. 2193-2200 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isoyama T, Kamoshita N, Yasui K, Iwai A, Shiroki K, Toyoda H, Takasaki Y, et al: "Lower concentration of La protein required for internal ribosome entry on hepatitis C virus RNA than on poliovirus RNA."J Gen Virol. 80. 2319-2327 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高崎芳成: "混合性結合組織病、内科学エッセンス"鈴木一、橋本博史編、朝倉書店. 3

    • Related Report
      1999 Annual Research Report
  • [Publications] 高崎芳成: "膠原病の内臓病変、内科学II"黒川清、松沢佑二編、文光堂. 4

    • Related Report
      1999 Annual Research Report
  • [Publications] Takasaki,Y et al: "Expression of cestimulatory molecule CD80 inperipheral blood T cells in patients with systemic lupus erythematosus" J.Rheumatol. 25. 1085-1071 (1998)

    • Related Report
      1998 Annual Research Report

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

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