Methods for predicting acute severe colitis treatment response
The present invention relates to methods for predicting acute severe colitis treatment response. Currently, there is no biomarker of drug 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 from 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 treating acute severe colitis (ASC) in a subject who has ASC, comprising
i) administering a corticosteroid to the subject;
ii) measuring, in a mucosal tissue sample obtained from the subject, before the step of administering and/or during at least the first five days of corticosteroid administration, the expression levels of hsa-miR-4423-3p, hsa-miR-3128, hsa-miR3152-3p, hsa-miR-603, hsa-miR-718, hp-hsa-mir-4259, hp_hsa-mir-193b, hp_hsa-mir-3934, hp-hsa-mir-3667, hp_hsa-mir-1260b, hsa-miR-938, hsa-miR-3150a-5p, hp_hsa-mir-100, hsa-miR-518b and hsa-miR-1468 miRNAs;
iii) detecting a higher expression level of each of hsa-miR-4423-3p, hsa-miR-3128, hsa-miR3152-3p and hsa-miR-603, and a lower expression level of each of hsa-miR-718, hp-hsa-mir-4259, hp_hsa-mir-193b, hp_hsa-mir-3934, hp-hsa-mir-3667, hp_hsa-mir-1260b, hsa-miR-938, hsa-miR-3150a-5p, hp_hsa-mir-100, hsa-miR-518b and hsa-miR-1468, compared to a reference value, in combination with the level of hemoglobin, hematocrit, albumin, C-reactive protein and transferrin expression, as indicative that a subject will be responsive to the corticosteroid; and
iv) administering the corticosteroid to the subject who will be responsive to the corticosteroid.
2. The method of claim 1 wherein the corticosteroid is methylprednisolone.
3. The method of claim 1 , wherein the expression levels of the miRNAs are compared to the reference value using a classification algorithm selected from deep learning classification, Linear Discriminant Analysis (LDA), Topological Data Analysis (TDA), Neural Networks and Random Forests algorithm (RF).
4. The method of claim 1 , further comprising a step of measuring at least one biological value selected from the group consisting of leukocyte, hematite, basophil and lymphocyte count, glucose, ferritin, and iron.