Formation of Antinuclear and Double-strand DNA Antibodies and Frequency of Lupus-like Syndrome in Anti-TNF-α Antibody-treated Patients with Inflammatory Bowel Disease

Background: Anti-tumor necrosis factor (TNF) therapy used in patients with inflammatory bowel disease (IBD) has been associated with induction of autoantibodies including antinuclear antibodies (ANA), double-strand (ds) DNA antibodies, and the occurrence of lupus-like syndrome (LLS). However, the clinical relevance of autoantibody formation and predictive factors are unclear. Methods: 180 IBD patients treated with anti-TNF antibodies (infliximab or adalimumab, or infliximab and adalimumab consecutively) were analyzed regarding ANA and dsDNA antibody values and the development of LLS, including factors predicting the development of LLS. Results: In all, 44.4% of anti-TNF-treated patients had ANA titers >= 1:240, while 15.6% had dsDNA serum levels >= 9 U/mL. However, only a minority of these patients experienced clinical symptoms of LLS; 8.9% presented with mild lupus-like symptoms with no need for intervention; 1.1% had severe symptoms consistent with LLS requiring immediate stop of anti-TNF therapy. Multivariate logistic regression analyses identified age as an independent risk factor for developing ANA >= 1: 240 (P < 0.001) and LLS (P = 0.002), while concomitant immunosuppressive therapy was protective against autoantibody formation (ANA: P = 0.05) and LLS development (P = 0.04). There was a significant association between dsDNA antibody values >= 9 U/mL and LLS (P = 0.02) but not between ANA titers and LLS. Conclusions: dsDNA antibody levels >= 9 U/mL, but not ANA titers >= 1:240, are associated with clinical symptoms of LLS. IBD patients of higher age treated with anti-TNF-alpha antibodies are at increased risk for development of ANA and LLS, while concomitant immunosuppressive therapy may have a protective effect.