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

Tumor necrosis factor-alpha (TNF-α) inhibitors are effective biologics for immune-mediated inflammatory diseases, including plaque psoriasis and inflammatory bowel disease (IBD). 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 three time points in 86 patients with plaque psoriasis receiving TNF-α inhibitor. We identified 3,351 time-course drug-response genes (DRGs), enriched in immune signaling and cell activation pathways and expressed in psoriatic skin lesion and blood. Among them, 259 genes showed differentially expressed between at least one pair of the three sampling time points and 962 were shared between psoriasis and IBD. TNF-α inhibitor responders showed higher expression of OLIG1, LRRK1, and KSR1, and lower expression of TNFAIP3 and MPP7 than non-responders. We identified a "red" gene co-expression module negatively correlated with treatment outcome and enriched in inflammation and TNF-related pathways. High expression of TNFSF10 (top hub gene of the "red" module) was associated with poor outcome. By week 2, the red module's co-expression pattern changed significantly in responders but not in non-responders. This study characterizes time-course peripheral blood transcriptional programs of TNF-α inhibitor therapy in plaque psoriasis.