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IgM antibody level against proinflammatory bacterial peptidoglycan is inversely correlated with extent of atherosclerotic disease

  • Manon M.Oude Nijhuis
    Affiliations
    Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center Utrecht, Room G02.523, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands

    Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands

    Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
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  • Yolanda van der Graaf
    Affiliations
    Julius Center, University Medical Center Utrecht, The Netherlands
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  • Marie-José Melief
    Affiliations
    Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
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  • Arjan H Schoneveld
    Affiliations
    Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center Utrecht, Room G02.523, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands

    Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
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  • Dominique P.V de Kleijn
    Affiliations
    Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center Utrecht, Room G02.523, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands

    Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
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  • Jon D Laman
    Affiliations
    Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
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  • Gerard Pasterkamp
    Correspondence
    Corresponding author. Tel.: +31-30-250-7155; fax: +31-30-252-2693.
    Affiliations
    Experimental Cardiology Laboratory, Heart Lung Center Utrecht, University Medical Center Utrecht, Room G02.523, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands
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  • for the SMART Studygroup, members listed in
    1
  • Author Footnotes
    1 A. Algra (M.D., Ph.D.), Julius Center for General Practice and Patient Oriented Research and Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands; J.D. Banga (M.D., Ph.D.), F.L.J. Visseren, T.J. Rabelink, Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; B.C. Eikelboom (M.D., Ph.D.), Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Y. van der Graaf (M.D., Ph.D.), D.E. Grobbee (M.D., Ph.D.), Julius Center for General Practice and Patient Oriented Research, University Medical Center Utrecht, Utrecht, The Netherlands; P.P.Th. de Jaegere (M.D., Ph.D.), Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands; L.J. Kappelle (M.D., Ph.D.), Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands; H.A. Koomans (M.D., Ph.D.), Department of Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands.

      Abstract

      Objective: Atherosclerosis may lead to acute clinical events by rupture of a vulnerable atherosclerotic plaque. Previously, we demonstrated that peptidoglycan (PGN), a major cell wall component of gram-positive bacteria that induces production of proinflammatory cytokines through TLR2 and CD14, is prevalent in atherosclerotic lesions with histological features associated with plaque vulnerability. We hypothesized that in atherosclerotic patients antibody levels against PGN may differ compared with matched controls. Methods and results: ELISA was performed to measure immunoglobulin levels against PGN in sera of 80 atherosclerotic patients versus 77 control patients with an increased cardiovascular risk, frequency-matched for age, sex and risk factors for atherosclerotic disease. In all patients and controls, intima-media (IMT) thickness was assessed using an array transducer. Significantly lower levels of IgM directed against PGN were found in atherosclerotic patients compared with the control patients without clinically manifested disease (P=0.02). The IgM levels against PGN decreased with increasing mean common carotid IMT thickness (P=0.006). Conclusions: These results show that patients suffering from atherosclerotic disease have decreased IgM levels against PGN. The data suggest that an antibody response against PGN could have a protective effect against the development or activity of atherosclerotic disease.

      Abbreviations:

      PGN (peptidoglycan), TLR (toll-like receptor), SMART (Second Manifestations of ARTerial disease), IMT (intima-media thickness), Ig (immunoglobulin), ABPI (ankle-brachial pressure index)

      Keywords

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