Infliximab, but not etanercept, induces IgM anti–double‐stranded DNA autoantibodies as main antinuclear reactivity: Biologic and clinical implications in autoimmune arthritis

Abstract

To analyze the clinical and biologic correlates of autoantibody induction during longer-term tumor necrosis factor alpha (TNFalpha) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept. Thirty-four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and antihistone, anti-nucleosome, and anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped. High numbers of infliximab-treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no further increase between year 1 and year 2 was observed. In contrast, induction of ANAs and anti-dsDNA antibodies was observed only occasionally in the etanercept-treated patients with SpA (10% of patients each). Isotyping revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus-related reactivities such as anti-ENA antibodies, antihistone antibodies, or anti-nucleosome antibodies, and no clinically relevant lupus-like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers. The prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNFalpha blockers, is largely restricted to short-term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment.