Fig. 5: Paradoxical enhancement of the IFN response in non-responders post-TNFi treatment.
a A plot of DEGs in monocytes for responders (Rs) and non-responders (NRs) before and after treatment with TNF inhibitor (TNFi). Each point represents a gene, colored by gene type as indicated in the lower right legend. b Bar graphs showing the proportion of genes in each quadrant, specifically highlighting R_only and NR_only genes. c Dot plot of Gene Ontology analysis for significant genes based on their response pattern, showing the top 5 terms per group, with red indicating higher significance. (Wilcoxon rank sum test (BH adjustment, two-sided)). d Schematic of in vitro experiments to assess the effect of adalimumab (ADA). Human PBMCs from four individuals were treated with TNFα for 12 h, followed by IgG1 control or ADA for 6 h prior to scRNA-seq. e The proportion change in the CXCL10hi cMo cluster in response to ADA treatment, with each dot representing one sample (n = 4, biological replicates). f Violin plots of normalized expression of SLAMF7 and JUN across four conditions. g A volcano plot of DEGs between ADA and control (IgG1), with red indicating downregulated genes and blue indicating upregulated genes (BH-adjusted P value). h Boxplots comparing the average expression of ADA-upregulated gene modules in Rs and NRs. Boxplot comparison (R n = 10, NR n = 12), two-sided t-test. i A 3D plot of baseline patient status defined by three variables, with arrows indicating the Pearson correlation between IFN\(\alpha \) score and delta ASDAS (upper left) and between the score and ADA-upregulated module (lower right). Each point represents a patient (blue for R, red for NR). j Plots of regulon specificity scores (RSS) based on the AUC in each condition. The top 10 regulons with the highest RSS are indicated by red circles. k Heatmap with binarized regulon activity. Regulons that showed significant differences between pre- and post-TNFi in the NR group are highlighted with red boxes. l Motif logos of the highest normalized enrichment score (NES) motifs for key transcription factors in the R and NR groups. m A PCA plot illustrating the contribution of different programs to the separation of Rs and NRs and their changes post-TNFi treatment, with ADA-up representing in vitro ADA-upregulated modules. Statistical analyses were performed using the unpaired t-test. Source data are provided as a Source Data file.
