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Arthritis development in arthralgia patients is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study
  1. Wouter H Bos (w.bos{at}janvanbreemen.nl)
  1. Jan van Breemen Instituut, Netherlands
    1. Gerrit Jan Wolbink (g.wolbink{at}janvanbreemen.nl)
    1. Jan van Breemen Instituut, Netherlands
      1. Maarten Boers (m.boers{at}vumc.nl)
      1. VU University Medical Center, Netherlands
        1. Gerard J Tijhuis (g.tijhuis{at}janvanbreemen.nl)
        1. Jan van Breemen Instituut, Netherlands
          1. Niek de Vries (niek.devries{at}amc.uva.nl)
          1. AMC/University of Amsterdam, Department of Clinical Immunology & Rheumatology, Netherlands
            1. Irene E van der Horst-Bruinsma (ie.vanderhorst{at}vumc.nl)
            1. VU University Medical Center, Netherlands
              1. Paul P Tak (p.p.tak{at}amc.uva.nl)
              1. AMC/University of Amsterdam, Department of Clinical Immunology & Rheumatology, Netherlands
                1. Rob van de Stadt (r.vd.stadt{at}janvanbreemen.nl)
                1. Jan van Breemen Instituut, Netherlands
                  1. Conny J van der Laken (j.vanderlaken{at}vumc.nl)
                  1. VU University Medical Center, Netherlands
                    1. Ben A C Dijkmans (bac.dijkmans{at}vumc.nl)
                    1. VU University Medical Center, Netherlands
                      1. Dirkjan van Schaardenburg (d.v.schaardenburg{at}janvanbreemen.nl)
                      1. Jan van Breemen Instituut, Netherlands

                        Abstract

                        Background: Anti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. We prospectively investigated the effect of ACPA presence and levels on arthritis development in arthralgia patients.

                        Methods: Arthralgia patients positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox-regression hazard analyses were used to calculate hazard ratios (HR) for arthritis development.

                        Results: 147 arthralgia patients were included (52 ACPA positive, 50 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range [IQR] 19-39), 29 patients developed arthritis in a median of 4 (IQR 3-6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR 6.0; 95% confidence interval [95% CI] 1.8-20.1; P = 0.003), but not of IgM-RF (HR 1.4, 95% CI 0.6-3.1) nor the SE (HR 1.5, 95% CI 0.7-3.0) was associated with arthritis development. Within the group of ACPA positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR 3.0; 95% CI 1.3-6.9; P = 0.01 and high ACPA levels (HR 1.7; 95% CI 1.1-2.5; P = 0.008), but not the SE (HR 1.0; 95% C.I. 0.5-2.1; P = 1.0).

                        Conclusion: In arthralgia patients the presence of ACPA, (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.

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