Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment

Abstract

The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30-6.75), 3.69 (2.67-4.62), 2.9 (2.39-4.65) and 3.71 (2.62-5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47-290 IU/ml) to 53 IU/ml (18-106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy.

Figure 1

Changes in disease activity in 30 patients with rheumatoid arthritis at different times during 78 weeks of infliximab therapy as determined by (a) Disease Activity Score (DAS 28) and (b) serum C-reactive protein (CRP) levels. The diamonds indicate median values, vertical bars indicate the interquartile range, and dotted lines indicate the upper normal limit.

Figure 2

Changes in the serum concentrations of (a) antinuclear antibodies (ANAs), (b) anti-double-stranded (ds)DNA antibodies, (c) anticardiolipin (aCL) IgG and (d) aCL IgM in 30 rheumatoid arthritis patients at different times during 78 weeks of infliximab treatment. In the graphs shown in panels b-d the reported values always remained below the upper normal limits, which were 30 IU/ml for anti-dsDNA antibodies, 10 U/ml for IgG aCl and 7 U/ml for IgM aCL. The diamonds indicate median values, and vertical bars indicate the interquartile range.

Figure 3

Changes in the serum titre of (a) rhematoid factor (RF) and (b) anti-cyclic citrullinated peptide (CCP) antibodies in 30 patients with rheumatoid arthritis at different times during 78 weeks of Infliximab treatment. The diamonds indicate median values, vertical bars indicate the interquartile range, and dotted lines indicate the upper normal limit.