Figure 2.

Normal infliximab dynamics correlated with changes in monocytes and reduced expression of innate immune-related pathways

(A) Cell frequency alterations following IFX treatment. Left panel, PCA presenting immune cell frequency changes following treatment based on 16 canonical immune populations determined by CyTOF. Arrow tail and head indicate the early W2 and later W14 relative to baseline compositional changes correspondingly. Ellipses represent the Euclidean distance from the center. Center panel, boxplots showing change in monocytes abundance following treatment relative to baseline in responders (n = 15) and non-responders (n = 8) (paired Wilcoxon p values shown). Right panel, scatterplot showing the relationship between changes in monocytes abundance (log-transformed fold change relative to baseline) and changes in CRP (fold change relative to baseline) (n = 23 for each time point, Spearman correlation = 0.4, p = 0.01).

(B) Venn diagram showing dynamic features that significantly changed over time at 2 weeks and 14 weeks post treatment compared with baseline for each response group using linear mixed-effects models (FDR <0.15, n = 1000 and n = 519 permutations for responders and non-responders, respectively).

(C) Scatterplot presenting the normal response network centrality of significantly enriched dynamic pathways at the early response period (GSEA, FDR <0.25, n perm = 1,000). Colors indicate pathway median fold-change expression at the early response period relative to baseline in responders (colored dots denote significant change in relative pathway score by Wilcoxon test, FDR <0.05).