Activated complement components and complement activator
molecules on the surface of cell-derived microparticles
in patients with rheumatoid arthritis and healthy
individuals
Eva Biro 1*, Rienk Nieuwland 1, Paul P Tak 2, Loes M Pronk 1, Marianne CL Schaap 1, Augueste Sturk 1 and C Erik Hack 3
1 Academic Medical Center, University of Amsterdam, Netherlands
2 AMC Amsterdam, Netherlands
3 Crucell, Leiden, Netherlands
* To whom correspondence should be addressed. E-mail: e.biro{at}amc.nl.
Accepted 21 January 2007
 | 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.
Keywords:
complement activation, microparticles, rheumatoid arthritis
