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Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals
  1. Eva Biro (e.biro{at}amc.nl)
  1. Academic Medical Center, University of Amsterdam, Netherlands
    1. Rienk Nieuwland (r.nieuwland{at}amc.nl)
    1. Academic Medical Center, University of Amsterdam, Netherlands
      1. Paul P Tak (p.p.tak{at}amc.uva.nl)
      1. AMC Amsterdam, Netherlands
        1. Loes M Pronk (lpronk{at}incresearch.com)
        1. Academic Medical Center, University of Amsterdam, Netherlands
          1. Marianne CL Schaap (m.c.schaap{at}amc.nl)
          1. Academic Medical Center, University of Amsterdam, Netherlands
            1. Augueste Sturk (a.sturk{at}amc.nl)
            1. Academic Medical Center, University of Amsterdam, Netherlands
              1. C Erik Hack (e.hack{at}crucell.com)
              1. Crucell, Leiden, Netherlands

                Abstract

                Objectives In vitro, microparticles can activate complement via the classical pathway. If demonstrable ex vivo, this mechanism may contribute to the pathogenesis of RA. We therefore investigated the presence of activated complement components and complement activator molecules on the surface of cell-derived microparticles of rheumatoid arthritis (RA) patients and healthy individuals.

                Methods Microparticles from synovial fluid (n=8) and plasma (n=9) of ten RA patients and plasma of sex- and age-matched healthy individuals (n=10) were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules [C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M, IgG].

                Results Microparticles with bound C1q, C4 and/or C3 were abundant in RA synovial fluid, while in RA and control plasma much lower levels were present. Microparticles with bound C1q correlated to those with bound C3 in synovial fluid (r=0.961, P=0.0001), and to those with bound C4 in plasma (RA: r=0.908, P=0.0007; control: r=0.632, P=0.0498), indicating classical pathway activation. In synovial fluid, microparticles with IgM and IgG correlated to those with C1q (r=0.728, P=0.0408; r=0.952, P=0.0003, respectively), and in plasma, microparticles with CRP correlated to those with C1q (RA: r=0.903, P=0.0021; control: r=0.683, P=0.0296), implicating IgG and IgM in the classical pathway activation in RA synovial fluid, and CRP in the low- level classical pathway activation in plasma.

                Conclusions This study demonstrates the presence of bound complement components and activator molecules on microparticles ex vivo, and supports their role in low-grade complement activation in plasma and increased complement activation in RA synovial fluid.

                • complement activation
                • microparticles
                • rheumatoid arthritis

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