Type I and II Interferon Signatures Can Predict the Response to Anti-TNF Agents in Inflammatory Bowel Disease Patients: Involvement of the Microbiota.

Abstract

Anti-TNF agents have been a cornerstone of IBD therapy; however, response to treatment has been variable, and clinically applicable biomarkers are urgently needed. We hypothesized that the type I and type II interferon (IFN) signatures may be a confounding factor for response to antitumor necrosis factor (TNF) treatment via interactions with the host and its gut microbiota. Peripheral blood from 30 IBD patients and 10 healthy controls was subjected to real-time quantitative real-time polymerase chain reaction for type I and type II IFN genes (IFNGs), both at baseline and after treatment with anti-TNF. Correlation between IFN signatures and microbiota composition was also determined for a subgroup of patients and controls. At baseline, type I IFN score was significantly higher in IBD patients (P = 0.04 vs controls). Responders to subsequent anti-TNF treatment had significantly lower baseline scores for both type I and II IFN signatures (P < 0.005 vs nonresponders for both comparisons). During treatment with anti-TNF, the expression of type I and II IFNGs was significantly elevated in responders and decreased in nonresponders. In addition, changes in IFN signatures correlated to specific alterations in the abundance of several microbial taxa of the gut microbiome. Baseline expression of type I and II IFN signatures and their kinetics during anti-TNF administration significantly correlate to treatment responses in IBD patients. Peripheral blood IFN signatures may serve as clinically meaningful biomarkers for the identification of subgroups of patients with favorable response to anti-TNF treatment. Additionally, the distinct synergies between different IFN types and microbiota might help drive therapeutic intervention.