Maarten Cozijnsen

79 Chapter 4 Infliximab impacts leukocyte RNA expression and serum inflammatory proteins ◀ Figure 1. Infliximab treatment homogeneously reduced intestinal inflammation in pediatric CD patients, reduced blood neutrophil counts and modulated both RNA expression of blood leukocytes and inflammatory protein concentrations in serum. Prednisolone, on the contrary, only reduced clinical disease activity, but had no significant effect on leukocyte counts, RNA expression or protein concentrations. In a randomized open-label trial, 11 newly diagnosed pediatric CD patients were treated with either infliximab (plus AZA) or with prednisolone (plus AZA). Disease activity was measured at week 0 and 10, and peripheral blood was drawn for RNA expression analysis at week 0 and 10 and serum for protein analysis at week 0 and 14. Compared to prednisolone, infliximab treatment not only reduced clinical disease activity, but also reduced fecal calprotectin concentration and endoscopic disease activity (A). It homogeneously lowered the number of circulating neutrophils and monocytes, and – to a lesser extend – lymphocytes (B). RNA expression analysis of whole blood revealed modulation by infliximab treatment of 949 genes (C). Serum protein analyses, using a proximity extension protein assay with 92 inflammatory proteins, revealed reduced concentrations of 34 of 92 inflammatory proteins (37%) after 14 weeks of top-down treatment (D). Prednisolone on the contrary had no significant effect on blood leucocyte counts, RNA expression or protein concentrations (B+C+D). Table 2. Pearson correlation between SESCD and Th1 related genes and proteins (n=18) Pearson correlation p-value IFNGR1 0.367 0.122 JAK2 0.692 0.001 STAT1 0.568 0.011 IRF1 0.633 0.004 CXCL9 0.820 <0.001 CXCL10 0.735 <0.001 CXCL11 0.742 <0.001 PD-L1 0.624 0.004 IFN-gamma 0.801 <0.001 IL-12B 0.524 0.021 IL-18 0.811 <0.001 IL-18R1 0.628 0.004