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Development of immunoabsorption therapy in patients with dilated cardiomyopathy

Research Project

Project/Area Number 13670753
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKANAZAWA MEDICAL UNIVERSITY

Principal Investigator

MATSUI Shinobu  KANAZAWA MEDICAL UNIVERSITY, Medical Research Institute, Professor, 総合医学研究所, 教授 (00064600)

Co-Investigator(Kenkyū-buntansha) HAYASE Mituru  KANAZAWA MEDICAL UNIVERSITY, Department of Clinical Pathology, Lecturer, 医学部, 講師 (90064592)
YAMAGUCHI Nobuo  KANAZAWA MEDICAL UNIVERSITY, Department of Serology, Professor, 医学部, 教授 (10106916)
KATSUDA Shogo  KANAZAWA MEDICAL UNIVERSITY, Department of Pathology, Professor, 医学部, 教授 (40110613)
KURIHARA Takayuki  KANAZAWA MEDICAL UNIVERSITY, Medical Research Institute, Lecturer, 総合医学研究所, 講師 (20064595)
ASAJI Takayosi  KANAZAWA MEDICAL UNIVERSITY, Department of Cardiology, Lecturer, 医学部, 講師 (00183137)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsdilated cardiomyopathy / β1-adrenoceptor / muscarinic-2 receptor / autoantibody / immunoabsorption / autoimmune disease / SCIDマウス / β_1受容体
Research Abstract

One of the main mechanisms for dilated cardiomyopathy is likely to be autoimmune-mediated myocardial damage. So far, a variety of autoantibodies have been detected against a number of putative autoantigen in the sera of patients with dilated cardiomyopathy. A growing body of studies have conformed that autoantibodies against, the second extracellular loop of β1-adrenoceptor and M2-muscarinic receptor are present in 30-40% of patients with dilated cardiomyopathy. These two autoantibodies posesses an 'agonist-like' effects on the target receptors. In order to elucidate whether the autoantibodies against these autoimmune epitopes play an important role in pathogenesis of dilated cardiomyopathy, we immunized rabbits over a period of one year with synthetic peptides corresponding to the second extracellular loop of the β1-adrenoceptor(β1-peptide) and the M2-muscarinic receptor(M2-peptide). These peptides induced morphological changes in the heart similar to those found in dilated cardiomyopathy. These clinical and experimental findings suggest that these anti-β1-adrenoceptor and M2-muscarinic receptor autoantibodies are of pathogenic importance in the development of dilated cardiomyopathy in vivo.
Based on these findings, we attempted to develope the immunoadborption colume which is able to extract anti-β1-adrenoceptor autoantibodies, selectively. The efficacy of this colume was about 70% against the sera of anti-β1-adrenoceptor autoantibody-positive absorbing-patients with dilated cardiomyopathy. Thereafter, rabbits immunized with β1-peptide or M2-peptide underwent immunoabsorption with anti-IgG colume. As a result, anti-IgG immunoabsorption therapy was performed safely and resulted in significant reduction of titer of anti-β1-adrenoceptor and M2-muscarmnic receptor autoantibodies. Now, we are trying to assess the effectiveness and safty using the rabbits with experimental autoimmue cardiomyopaty induced by immunization of β1-peptide.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Matsui S: "Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor"J Cardiovasc Pharmacol. 38(Suppl.1). 217-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S: "Prevention of experimental autoimmune cardiomyopathy in rabbits by receptor blockers"Autoimmunity. 34. 217-220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zong ZP: "Growth hormone interferes with the progression of myocarditis in rats"Eur J Pharmacol. 415. 51-60 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Song BC: "Methimazole interferes with the progression of experimental autoimmune myocarditis in rats"Autoimmunity. 34. 265-274 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S: "Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice."J Cardiovasc Pharmacol. 42(Suppl.1). S99-S103 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S: "Amiodarone minimizes experimental autoimmune myocarditis in rats"Eur J Pharmacol. 469. 165-173 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S, et al.: "Beneficial effect of muscarinic-2 antagonist on dilated cardiomyopathy induced by autoimmune mechanism against muscarinic-2 receptor."J Cardiovasc Pharmacol. 38(Suppl.1). S43-S49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S, et al.: "Prevention of experimental autoimmune cardiomyopathy in rabbits by receptor blockers."Autoimmunity. 34. 217-220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zong ZP, et al.: "Growth hormone interferes with the progression of myocarditis in rats."Eur J Pharmacol. 415. 51-60 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Song BC, et al.: "Methimazole interferes with the progression of experimental autoimmune myocarditis in rats."Autoimmunity. 34. 265-274 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S, et al.: "Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice."J Cardiovasc Pharmacol. 42(Suppl.1). S99-S103 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S, et al.: "Amiodarone minimizes experimental autoimmune myocarditis in rats."Eur J Pharmacol. 469. 165-173 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui S: "Transfer of rabbit autoimmune cardiomyopathy into severe combined immunodeficiency mice."J caardiovasc Pharmacol. 42(suppl 1). SS99-S103 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsui S: "Amiodarone minimizes experimental autoimmune myocarditis."Eur J Pharmacol. 469. 165-173 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsui S.: "Beneficial Effect of Muscarinic-2 Antagonist on Dilated Cardiomyopathy Induced by Autoimmune Mechanism against Muscarinic-2 Receptor"J Cardiovasc. Pharmacol. 38(Suppl.1). S43-S49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsui S.: "Prevention of Experimental Autoimmune Cardiomyopathy in Rabbits by Receptor Blockers"Autoimmunity. 34. 217-220 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Song B.C.: "Methimazole interferes with the progression of experimental autoimmune myocarditis in rats"Autoimmunity. 34. 265-274 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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