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J Rheumatol. 2008 Oct;35(10):1972-7. Epub 2008 Sep 1.

Differential response of the rheumatoid factor and anticitrullinated protein antibodies during adalimumab treatment in patients with rheumatoid arthritis.

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  • 1Jan van Breemen Instituut, Sanquin Research, and VU University Medical Center, Department of Rheumatology, Amsterdam, The Netherlands.



To investigate the effect of anti-tumor necrosis factor (TNF) treatment on rheumatoid factor (IgM-RF) and anticitrullinated protein antibodies (ACPA) and its association with treatment response and acute-phase reactants.


In a cohort of 188 consecutive patients with rheumatoid arthritis (RA) treated with adalimumab, baseline IgM-RF and ACPA were determined by ELISA, and compared to levels after 28 weeks of treatment. ACPA were measured as antibodies to cyclic citrullinated peptide (anti-CCP). The relative change of antibody levels was correlated to the European League Against Rheumatism response criteria and to the change in acute-phase reactants [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)].


The median decline in IgM-RF levels was greater than the decline in ACPA levels (31% vs 8%; p<0.001). The decrease in antibody levels was greater in the group of good responders than in the group of nonresponders [43% vs 7% for IgM-RF (p<0.0001) and 16 vs -4% for ACPA (p=0.03)]. Seventeen percent of IgM-RF-positive patients at baseline turned negative at 28 weeks; this qualitative effect was not observed for ACPA. Further, the decline in IgM-RF, but not ACPA, was associated with a decrease in CRP and ESR (p=0.004 and p=0.006, respectively).


TNF treatment directly influences IgM-RF and ACPA levels, but in those responding to treatment only. The effect on IgM-RF levels and positivity status is greater than on ACPA levels and is associated with the decline in markers of inflammation. These results further emphasize the differential role these autoantibodies may play in RA; IgM-RF as marker of inflammatory activity, and ACPA as qualitatively stable hallmark of RA.

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