Low serum deoxyribonuclease I activity is associated with antiTNF-alpha induced skin adverse events in patients with inflammatory bowel disease

Abstract

Background: A significant proportion of inflammatory bowel disease (IBD) patients develop skin complications during infliximab or adalimumab therapy. Both drugs are thoughtto act via induction of apoptosis in activated inflammatory cells. Deoxyribonuclease (DNase) I is endonuclease hydrolyzing double-stranded DNA during apoptosis and its deficiency has been implicated in several autoimmune disorders.

Aim: To assess activity of DNase I in patients with IBD and to identify its impact together with other factors on development of skin immunopathological complications of biological therapy.

Methods: IBD patients treated with infliximab or adalimumab at our centre from 2007-2009 were studied retrospectively for occurrence of skin non-infectious complications during this treatment and assessed for DNase I activity. A random sample of IBD patients treated with biological therapy without skin complications was also assessed. Serum was used to determine DNase I activity by enzyme-linked immunosorbent assay.

Results: During the study period 313 patients with IBD were treated with biological therapy. Of them, 43 patients experienced non-infectious skin complications. 95 IBD patients on biological therapy without skin complications were also included. Univariate analysis identified female gender, adalimumab therapy, no concomitant corticosteroids and low DNase I activity as risk factors for skin complications. In multivariate analysis only low activity of DNase I (OR 0.45; 95% CI 0.29-0.71; p < 0.001) and adalimumab therapy (OR 30.8; 95% CI 6.87-138.16; p < 0.001) were associated with skin adverse events.

Conclusions: Low DNase I activity may be a risk factor for development of immune-mediated skin complications during biological therapy in patients with IBD.