Methods for predicting acute severe colitis treatment response

Abstract

The present invention relates to methods for predicting acute severe colitis treatment response. Currently, there is no biomarker of drag response. The present invention provides the first prediction tool for responses to first- and second-line treatments in acute severe ulcerative colitis. Putative mRNA targets of dysregulated microRNAs were identified from patient biopsies. One classifier of fifteen colonic microRNAs plus five biological values at admission were identified with a prediction accuracy of 96.6% for discriminating responders from non-responders to steroids. Using a similar method, 6 and 4 mucosal microRNA-based algorithms were identified to classify responders from non-responders to infliximab and cyclosporine. In particular, the present invention relates to methods for predicting acute severe colitis treatment response by measuring the expression levels of several miRNAs selected front the group consisting of hp_hsa-mir-3934, hp_hsa-mir-100, hsa-miR-718, hp_hsa-mir-193b, hsa-miR-3150a-5p, hp_hsa-mir-1260b, hsa-miR-938, hsa-miR-518b and hsa-miR-1468.

1 . A method of determining whether a subject suffering from acute severe colitis (ASC) will be a responder or a non-responder to an anti-TNFα drug, comprising the steps of i) measuring in a mucosal tissue sample obtained from said subject before or during the first days of anti-TNFα drug administration the expression level of at least one miRNA selected from the group consisting of hsa-miR-4423-3p, hsa-miR-3128, hsa-miR-3152-3p, hp_hsa-mir-193b, hsa-miR-938 and hp_hsa-mir-100, ii) comparing the expression level measured at step i) with a reference value, and iii) detecting differences in the expression level between the mucosal tissue sample and the reference value is indicative that said subject will be a responder or a non-responder. 
     
     
         2 . The method of  claim 1  wherein the anti-TNFα drug is infliximab 
     
     
         3 . A method of determining whether a subject suffering from acute severe colitis (ASC) will be a responder or a non-responder to an anti-TNFα drug, comprising the steps of i) measuring in a mucosal tissue sample obtained from said subject before or during the first days of anti-TNFα drug administration the expression level of the miRNAs selected from the group consisting of hp_hsa-mir-100, hsa-miR-938 and hsa-miR-518b ii) comparing the expression level measured at step i) with a reference value, and iii) detecting differences in the expression level between the mucosal tissue sample and the reference value is indicative that said subject will be a responder or a non-responder. 
     
     
         4 . The method of  claim 3  wherein the anti-TNFα drug is infliximab