Time-course blood transcriptome dynamics of TNF-α inhibitor therapy in a Chinese cohort with psoriasis.

TNF-α inhibitors are effective biologics for immune-mediated inflammatory diseases, including plaque psoriasis and inflammatory bowel disease. However, time-course peripheral blood transcriptomic changes during treatment remain poorly characterized. To characterize transcriptomic changes associated with TNF-α inhibitor treatment, we profiled blood transcriptomics at 3 time points in 86 patients with plaque psoriasis receiving a TNF-α inhibitor. We identified 3351 time-course drug-response genes that were enriched in immune signaling and cell activation pathways and expressed in psoriatic skin lesions and blood. Among them, 259 genes were differentially expressed between at least 1 pair of the 3 sampling time points, and 962 were shared between psoriasis and inflammatory bowel disease. TNF-α inhibitor responders showed higher expression of OLIG1, LRRK1, and KSR1 and lower expression of TNFAIP3 and MPP7 than nonresponders. We identified a "red" gene coexpression module that was negatively correlated with treatment outcome and enriched in inflammation and TNF-related pathways. High expression of TNFSF10 (the top hub gene of the "red" module) was associated with a poor outcome. By week 2, the red module's coexpression pattern had changed significantly in responders but not in nonresponders. This study characterizes the time-course peripheral blood transcriptional programs of TNF-α inhibitor therapy in plaque psoriasis.

Abstract from PubMed