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Preferential decrease of IgG4 anti-citrullinated protein antibodies during treatment with TNF blocking agents in patients with rheumatoid arthritis
  1. Wouter H Bos (w.bos{at}janvanbreemen.nl)
  1. Sanquin Research, Amsterdam, Netherlands
    1. Geertje M Bartelds (m.bartelds{at}janvanbreemen.nl)
    1. Jan van Breemen Institute, Netherlands
      1. Marijn Vis (m.vis{at}vumc.nl)
      1. VU University medical center, Netherlands
        1. Ann R van der Horst (a.vanderhorst{at}sanquin.nl)
        1. Sanquin Diagnostic Services, Amsterdam, Netherlands
          1. Gerrit Jan Wolbink (g.wolbink{at}janvanbreemen.nl)
          1. Jan van Breemen Institute, Netherlands
            1. Rob van de Stadt (r.vd.stadt{at}janvanbreemen.nl)
            1. Jan van Breemen Institute, Netherlands
              1. Dirkjan van Schaardenburg (d.v.schaardenburg{at}janvanbreemen.nl)
              1. Jan van Breemen Institute, Netherlands
                1. Ben AC Dijkmans (bac.dijkmans{at}vumc.nl)
                1. VU University medical center, Netherlands
                  1. Willem F Lems (wf.lems{at}vumc.nl)
                  1. VU University medical center, Netherlands
                    1. Michael T Nurmohamed (m.nurmohamed{at}janvanbreemen.nl)
                    1. VU University medical center, Netherlands
                      1. Lucien Aarden (l.aarden{at}sanquin.nl)
                      1. Sanquin Research, Amsterdam, Netherlands
                        1. Dorte Hamann (d.hamann{at}sanquin.nl)
                        1. Sanquin Diagnostic Services, Amsterdam, Netherlands

                          Abstract

                          Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibodies (ACPA) subclasses during anti-TNF treatment in patients with rheumatoid arthritis (RA).

                          Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on citrullinated fibrinogen (ACF) and IgG1:IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks.

                          Results: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4:IgG1 ACF ratio in the infliximab cohort. In the adalimumab treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4:IgG1 ratio was reduced by 24% (all percentage values P < 0.05). The decrease in antibody levels was correlated with the clinical response; EULAR good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4:IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels.

                          Conclusion: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4:IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on the chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.

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