Maarten Cozijnsen

81 Chapter 4 Infliximab impacts leukocyte RNA expression and serum inflammatory proteins ◀ Figure 2. Infliximab treatment homogeneously reduced RNA expression of Th1 related genes in peripheral blood leukocytes and serum concentration of Th1 related proteins In a randomized open-label trial, 11 newly diagnosed pediatric CD patients were treated with either infliximab (plus AZA) or received conventional treatment with prednisolone (plus AZA). Blood samples were taken for measurement of RNA expression and protein concentrations at baseline and again at week 10 (RNA) or week 14 (protein). RNA expression analysis revealed significant downregulation of the Th1 related genes IFNGR1, JAK2, STAT1 and IRF1 in patients treated with infliximab (A). Protein analysis agreed with this pattern by showing reduced concentrations of the Th1 related proteins CXCL9, CXCL10 and CXCL11, PD-L1, IFN-gamma, IL-12B, IL-18 and IL-18R1 in infliximab treated patients (B). This pattern was not seen in patients treated with prednisolone, showing instead a more heterogeneous treatment response (A+B). Table 3. Pearson correlation between SESCD and s100 calcium binding proteins and neutrophil chemo attractants (n=18) Pearson correlation p-value S100A6 0.832 <0.001 S100A8 0.736 <0.001 S100A9 0.823 <0.001 S100A12 0.668 0.002 CXCL1 0.551 0.014 CXCL5 0.272 0.259 CXCL8 0.354 0.137 EN-RAGE (S100A12) 0.433 0.064 Infliximab treatment reduces transcription and concentration of proteins involved in tissue remodeling RNA expression analysis revealed downregulation of the expression of mRNA TGFA , OSM , TNFSF14 and MMP9 in blood of infliximab treated patients (Figure 4A). All these proteins, except for MMP9 – which was not part of the PEA kit – were also found reduced in serum, as were LAP TGF-beta-1, VEGF-A, IL-6, LIF-R, TWEAK (TNFSF12), OPG and MMP-1 (Figure 4B). Both RNA expression of TGFA , OSM and TNFSF14 in blood leukocytes and serum concentrations of LAP TGF-beta-1, VEGF-A, OSM, IL-6, LIF-R and MMP-1 were all positively associated with SESCD (Table 4). MMP9 RNA expression in blood leukocytes and TGF-alpha and TWEAK (TNFSF12) serum concentrations were associations with SESCD with a p-value between 0.05 and 0.01.