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Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis
  1. I C van Eijk1,*,
  2. M E Tushuizen2,
  3. A Sturk3,
  4. B A C Dijkmans4,
  5. M Boers5,
  6. A E Voskuyl6,
  7. M Diamant2,
  8. G.J. Wolbink5,
  9. R Nieuwland3,
  10. M T Nurmohamed5
  1. 1 Jan van Breemen Institute, Netherlands;
  2. 2 Department of Endocrinology, VU University Medical Center, Netherlands;
  3. 3 Laboratory for Experimental Clinical Chemistry, Academic Medical Center, Netherlands;
  4. 4 VU University Medical Center, Netherlands;
  5. 5 Department of Rheumatology, Jan van Breemen Institute, Netherlands;
  6. 6 Department of Rheumatology, VU University Medical Center, Netherlands
  1. Correspondence to: I.C. van Eijk, Rheumatology, Jan van Breemen Institute, Dr. Jan van Breemenstraat, Amsterdam, 1056 AB, Netherlands; i.v.eijk{at}janvanbreemen.nl

Abstract

Objectives: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovitis and joint destruction. The pathogenesis of RA is not clear, but is considered to be an immune-mediated inflammatory disorder, in which the complement system plays an important role. Although cell-derived microparticles (MP) have been associated with inflammation and complement activation, it is unknown whether MP are either cause or consequence. Therefore, we investigated whether circulating MP differ between very early yet untreated arthritis patients and healthy controls, and whether intensive anti-inflammatory treatment of such patients affects circulating MP.

Methods: RA patients (n=24) and controls (n=15) were included. Nine RA patients were re-evaluated after 8 weeks of intensive treatment with a combination of drugs (COBRA-scheme). Disease activity was measured by ESR, C-reactive protein (CRP) and disease activity score of 28 joints (DAS28). Flow cytometry was used to study MP and exposure of complement activator molecules and complement components.

Results: At baseline, concentrations of MP exposing C1q, CRP or SAP were all significantly elevated in early RA patients compared to controls (p=0.003, p=0.002, and p=0.003, respectively). Upon treatment, DAS28, ESR and CRP significantly decreased (P=0.008, P=0.008 and P=0.012), but the concentrations of circulating MP and MP exposing complement components or activator molecules were unaffected.

Conclusion: Circulating MP exposing complement components or activator molecules are elevated in early RA. Since a strong anti-inflammatory therapy suppressed inflammation in early RA patients but not levels of circulating MP, it is unlikely that inflammation is the main underlying cause of MP release in these patients.

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