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HMG proteins : their intra-cellular trafficking and the role in inflammatory diseases

Research Project

Project/Area Number 10470125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OZAKI Shoichi  Kyoto Univ., Grad. Sch. Med, Lecturer, 医学研究科, 講師 (00231233)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Michiteru  Science Univ Tokyo, Professor, 基礎工学部, 教授 (20005648)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsHMG proteins / HMG1 / HMG2 / anti-HMG antibody / autoimmune disease / Autoimmune hepatitis / epitopes / intra-cellular localization / 抗好中球細胞質抗体 / 炎症性疾患 / amphoterin / 自己抗体
Research Abstract

We found the existence of anti-HMG1/HMG2 antibodies in 89% of patients with autoimmune hepatitis. These antibodies seemed to be useful clinical markers in the disease based on the highest prevalence and the correlation with disease activity.
To determine the B-cell epitopes recognized by circulating autoantibodies, we performed western blotting, in which antigens were a set of recombinant fragment peptides of HMG1 and HMG2. Antibody-positive sera from patients with autoimmune hepatitis were used. Our results indicated that the epitopes are located within a linker region between the two HMG boxes.
We also investigated the mechanism of the selective staining of neutrophil by anti-HMG1/HMG2 antibodies. Affinity-purified anti-HMG1/HMG2 antibodies from patient serum reacted only with neutrophils, but not with lymphocytes, HEp-2 or HL60 cells(a promyelocytic leukemia cell line) in indirect immunofluorescence. After HL60 were treated with all-trans retinoic acid to induce granulocyte differentiation, however, these cells became reactive to the antibodies. In western blotting, the antibodies showed a distinct pattern of bands in neutrophils and differentiated HL60 cells, which was different from those in lymphocytes and untreated HL60 cells. Northern blotting revealed no significant difference in mRNA of HMG1 and HMG2 during differentiation of HL60 cells. These results indicated that the epitopes of HMG1/HGM2 molecules in neutrophils are disclosed or modified to become reactive to the antibodies during granulocyte differentiation.
The linker region, which we determined to be the major epitope, is known to be necessary for the nuclear localization of HMG proteins. It seems therefore that the change of antigenicity of the region may affect the nuclear localization signal and the efficiency of transcription in mature neutrophils.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Sobajima J., Ozaki S., et al.: "Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis"Clin. Exp. Immunol.. 111・2. 402-407 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uesugi H., Ozaki S., et al.: "Prevalence and characterization of novel P-ANCA, antibodies to the high mobilty group non-histone chromosomal proteins HMGI and HMG2, in systemic rheumatic diseases"J. Rheumatol.. 25. 703-709 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka M., Ozaki S., et al.: "Cloning of follistatin-related protein (FRP) as a novel autoantigen in systemic rheumatic diseases"Int. immunol.. 10・9. 1305-1314 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sobajima J., Ozaki S., et al.: "High mobility group non-histone chromosomal proteins HMGI and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoinnune hepatitis"Gut. 44・6. 867-873 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinkura N., Ozaki S., et al.: "Autoantibodies to FK506 binding protein 12 (FKBP12) in autoimmune diseases"Autoimmunity. 29. 159-170 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ochiai k., Ozaki S.,et al: "Genetic regulation of anti-erythrocyte autoantibodeis and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice"Int. immunol.. 12・1. 1-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 尾崎承一(共著): "わかりやすい内科学"文光堂(東京)、井村裕夫、主幹編集. 1178 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 尾崎承一(共著): "内科学"文光堂(東京)、黒川清、松澤佑次、主幹編集. 2233 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sobajima J., Ozaki S., Uesugi H., Osakada F., Shirakawa H., Yoshida M., Nakao K.: "Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis."Clin. Exp. Immunol.. 111 (2). 402-407 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uesugi H., Ozaki S., Sobajima J., Osakada F., Shirakawa H., Yoshida M., Nakao K.: "Prevalence and characterization of novel P-ANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases."J. Rheumatol.. 25. 703-709 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka M., Ozaki S., Osakada F., Mori K., Nakao K.: "Cloning of follistatin-related protein (FRP) as a novel autoantigen in systemic rheumatic diseases."Int. Immunol.. 10 (9). 1305-1314 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shinkura N., Ikai I., Yamauchi A., Hirose T., Kawai Y., Inamoto T., Ozaki S., Iwai M., Bona C., Yamaoka Y.: "Autoantibodies to FK506 binding protein 12 (FKBP 12) in autoimmune diseases."Autoimmunity. 29. 159-170 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sobajima J., Ozaki S., Uesugi H., Osakada F., Inoue M., Fukuda Y., Shirakawa H., Yoshida M., Rokuhara A., Imai H., Kiyosawa K., Nakao K.: "High mobility group non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis."Gut. 44 (6). 3107-3314 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ochiai K. *, Ozaki S. *, Tanino A., Watanabe S., Ueno T., Mitsui K., Toei J., Inada Y., Hirose S., Shirai T., Nishimura H. (* the first two authors contributed equally to this work): "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice."Int. Immunol.. 12 (1). 1-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sobajima J.,Ozaki S.et al.: "Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis"Clin. Exp. Immunol.. 111・2. 402-407 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uesugi H.,Ozaki S.et al.: "Prevalence and characterization of novel P-ANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases"J. Rhenmatol.. 25. 703-709 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka M.,Ozaki S.et al.: "Cloning of follistatin related protein (FRP) as a novel autoantigen in systemic rheumatic diseases"Int. Immunol.. 10・9. 1305-1314 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sobajima J.,Ozaki S.et al.: "High mobility group non histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis"Gut. 44・6. 867-873 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shinkura N.,Ozaki S.et al.: "Autoantibodies to FK506 binding protein 12 (FKBP12) in autoimmune diseases"Autoimmunity. 29. 159-170 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ochiai K.,Ozaki S.et al.: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice"Int. Immunol.. 12・1. 1-8 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 尾崎承一(共著): "わかりやすい内科学"文光堂(東京)、井村裕夫・主幹編集. 1178 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 尾崎承一(共著): "内科学"文光堂(東京)、黒川清・松澤佑次・主幹編集. 2233 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sobajima J., Ozaki S., et al.: "Prevalence and characterization of P-ANCA directed against HMG1 and HMG2 in ulcerative colitis." Clin.Exp.Immunol.111・2. 402-407 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uesugi H., Ozaki S., et al.: "Prevalence and characterization of novel P-ANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases." J.Rheumatol.25. 703-709 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka M., Ozaki S., et al.: "Cloning of follistatin-related protein(FRP)as a novel autoantigen in systemic rheumatic diseases." Int.Immunol.10・9. 1305-1314 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinkura N., Ozaki S., et al.: "Autoantibodies to FK506 binding protein 12(FKBP12)in autoimmune diseases." Autoimmunity. (発表予定).

    • Related Report
      1998 Annual Research Report
  • [Publications] Sobajima J., Ozaki S., et al.: "High mobility group non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoinnune hepatitis." Gut. (発表予定).

    • Related Report
      1998 Annual Research Report
  • [Publications] 尾崎承一(共著): "自己免疫でおこる難治性疾患-実地医家のための最新情報-" 医薬ジャーナル社(東京)、坂根剛・編, 267

    • Related Report
      1998 Annual Research Report
  • [Publications] 尾崎承一(共著): "外来診療のすべて(改訂第2版)" メディカルビュー社(大阪)、高久史麿・総監修, 911

    • Related Report
      1998 Annual Research Report

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

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