A blood-based model driven by mitochondrial dysfunction predicts anti-TNF response during ulcerative colitis
Recent studies hint at mitochondrial genes influencing UC patient response to anti-TNF treatment. We evaluated this hypothesis by following a targeted strategy to identify a gene signature that captures the relationship between mitochondrial dysregulation and response to treatment. We analyzed the transcriptome of colon samples from an anti-TNF treated murine model characterized by impaired mitochondrial activity and treatment resistance. We then transferred the findings that linked mitochondrial dysfunction and compromised treatment response to an anti-TNF treated UC human cohort. We next matched differential expression in the blood using monocytes from peripheral blood of controls and IBD patients. The resulting genes were used in a predictive model, validated with blood samples from UC patients at baseline in an external dataset, and showed strong specificity for anti-TNF treatment.