Formation Of Antinuclear And Double-Strand Dna Antibodies And Frequency Of Lupus-Like Syndrome In Anti-Tnf-Alpha 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.