Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Effect of Disease Modifying Anti-Rheumatic Drugs (DMARDs) On Anti-CCP2 and Anti-Citrullinated Protein Antibody (ACPA) Levels During Longitudinal Assessments In Rheumatoid Arthritis Patients.
Soejima1, Makoto, Patel1, Aarat M., Goudeau1, Danielle, Jones1, Donald M., Amity1, Christine L., Frydrych1, Lynne M., McBride1, Dawn
Anti-citrullinated protein antibodies (ACPA) are specific markers for rheumatoid arthritis (RA) and may have a pathogenic role in the development of rheumatoid synovitis. ACPA are produced by B cells and some studies suggest that TNF regulates B cell development. Therefore, the purpose of these studies was to determine the effect of TNF antagonists on ACPA levels and to correlate these changes with changes in B cell subsets in patients with RA.
115 RA patients with 3 longitudinal samples in the University of Pittsburgh Medical Center Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry and 226 RA patients with 4 longitudinal samples in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) study were clinically assessed at each visit. Quantitative serum levels of ACPA were measured using ELISAs. B cell subsets were analyzed using flow cytometry. The effect of treatment on ACPA levels and on B cell subset numbers were analyzed using a mixed effects regression model, ANOVA, and t-test. Disease activity was controlled for in the analyses.
Age, sex, race, rheumatoid factor (RF), and disease activity scores at baseline were similar among the different treatment groups within each cohort. ACPA levels changed following therapy and changes in ACPA levels were similar in the TEAR and RACER cohorts. ACPA levels decreased during the first 6 months of oral DMARD and TNF antagonist therapy. After 6 months, ACPA levels declined further in patients treated with oral DMARDs but returned to baseline levels in patients treated with TNF antagonists. This resulted in significant differences in ACPA levels between these groups (for TEAR subjects, p=0.0015 for anti-CCP2 (cyclic citrullinated peptide), p=0.0045 for anti-P6c (citrullinated fibrinogen peptide) and p=0.0058 for anti-P20c (citrullinated fillagrin peptide)). The percentages of pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells in RA patients treated with TNF antagonists were significantly lower than in healthy control subjects and subjects treated with oral DMARDs only (p=0.0018 and p=0.0018, respectively). The percentage of naïve B cells was higher among RA subjects treated with TNF antagonists compared to subjects treated with oral DMARDs only (p=0.0068).
We found a differential effect of oral DMARD therapy versus anti-TNF therapy on ACPA levels in patients with RA. After 612 months of treatment, TNF therapy was associated with an increase in ACPA levels, a lower percentage of peripheral blood (PB) pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells and with an increase in naïve B cells. Naïve B cells in RA patients as compared to healthy subjects have been reported to produce higher levels of autoreactive antibodies. Taken together, these studies suggest that TNF blockade in RA patients may initially lower ACPA levels via diminished inflammation within the synovium where ACPA are produced. However, TNF blockade later leads to increased numbers of naïve autoreactive B cells that subsequently lead to increased ACPA levels.
To cite this abstract, please use the following information:
Soejima, Makoto, Patel, Aarat M., Goudeau, Danielle, Jones, Donald M., Amity, Christine L., Frydrych, Lynne M., et al; Effect of Disease Modifying Anti-Rheumatic Drugs (DMARDs) On Anti-CCP2 and Anti-Citrullinated Protein Antibody (ACPA) Levels During Longitudinal Assessments In Rheumatoid Arthritis Patients. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :393