Maarten Cozijnsen

83 Chapter 4 Infliximab impacts leukocyte RNA expression and serum inflammatory proteins ◀ Figure 3. Infliximab treatment reduced RNA expression of several s100 calcium-binding proteins – predominantly expressed in neutrophils – and reduced concentrations of chemokines involved in neutrophil recruitment, which reflects a reduced neutrophil signature In a randomized open-label trial, 11 newly diagnosed pediatric CD patients were treated with either infliximab (plus AZA) or received conventional prednisolone treatment (plus AZA). Blood samples were taken for measurement of leukocytes RNA expression and serum protein concentrations at baseline and again at week 10 (RNA) or week 14 (protein). RNA expression analysis revealed downregulation of S100A6, S100A8, S100A9 and S100A12 in blood leukocytes of infliximab treated patients, which are predominantly expressed by neutrophils (A). EN-RAGE (S100A12) concentrations were also reduced in sera of infliximab treated patients (B). Moreover, reduced serum concentrations of CXCL1, CXCL5 and CXCL8 were found; chemokines that are known to recruit CXCR1/2+ neutrophils (B). These treatment effects were not detected in prednisolone treated patients. Table 4. Pearson correlation between SESCD and proteins involved in tissue remodeling (n=18) Pearson correlation p-value TGFA 0.734 <0.001 OSM 0.872 <0.001 TNFSF14 0.617 0.005 MMP9 0.527 0.02 TGF-alpha 0.576 0.01 LAP TGF-beta-1 0.694 0.001 VEGF-A 0.601 0.006 OSM 0.753 <0.001 IL-6 0.758 <0.001 LIF-R 0.612 0.005 TWEAK (TNFSF12) 0.515 0.024 LIGHT (TNFSF14) 0.239 0.325 OPG 0.245 0.312 MMP-1 0.716 0.001