Abstract
Treatment of rheumatoid arthritis (RA) with infliximab (Remicade®) has been associated with the induction of antinuclear autoantibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) autoantibodies. In the present study we investigated the humoral immune response induced by infliximab against organ-specific or non-organ-specific antigens not only in RA patients but also in patients with ankylosing spondylitis (AS) during a two-year followup. The association between the presence of autoantibodies and clinical manifestations was then examined. The occurrence of the various autoantibodies was analyzed in 24 RA and 15 AS patients all treated with infliximab and in 30 RA patients receiving methotrexate but not infliximab, using the appropriate methods of detection. Infliximab led to a significant induction of ANA and anti-dsDNA autoantibodies in 86.7% and 57% of RA patients and in 85% and 31% of AS patients, respectively. The incidence of antiphospholipid (aPL) autoantibodies was significantly higher in both RA patients (21%) and AS patients (27%) than in the control group. Most anti-dsDNA and aPL autoantibodies were of IgM isotype and were not associated with infusion side effects, lupus-like manifestations or infectious disease. No other autoantibodies were shown to be induced by the treatment. Our results confirmed the occurrence of ANA and anti-dsDNA autoantibodies and demonstrated that the induction of ANA, anti-dsDNA and aPL autoantibodies is related to infliximab treatment in both RA and AS, with no significant relationship to clinical manifestations.
Highlights
Clinical trials in rheumatoid arthritis (RA) have demonstrated that antibodies directed against tumor necrosis factor α(TNF-α) are highly beneficial for most patients who are refractory to classic treatment with disease-modifying anti-rheumatic drugs, methotrexate or steroid therapy [1,2,3,4]
Occurrence of ANA and anti-dsDNA autoantibodies in RA and ankylosing spondylitis (AS) patients At baseline, 9 of 24 (37.5%) infliximab-treated RA patients, 2 of 15 (13.3%) AS patients and 5 of 30 (16.7%) control RA patients were tested positive for ANA (Table 2)
Our results show that infliximab induces ANA, anti-dsDNA and aPL autoantibodies at various times after the start of treatment
Summary
Clinical trials in rheumatoid arthritis (RA) have demonstrated that antibodies directed against tumor necrosis factor α(TNF-α) (adalimumab, infliximab [Remicade®]) are highly beneficial for most patients who are refractory to classic treatment with disease-modifying anti-rheumatic drugs, methotrexate or steroid therapy [1,2,3,4]. These antiinflammatory effects of infliximab have led to their use in other inflammatory diseases such as Crohn's disease [5]. Only a few cases of SLElike syndrome have been reported in infliximab-treated patients [9,13,16,17,18]
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