THE USE OF IMMUNOSTAINING IN BIOPSIES TO EVALUATE EXPRESSION PATTERN AND PATHOPHYSIOLOGY ROLES OF ONCOSTATIN M AND ITS RECEPTOR BETA IN PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract

Abstract INTRODUCTION The mRNA expression of oncostatin M (OSM) in colonic tissue is raised in inflammatory bowel disease (IBD) and is mplicated in anti-TNF treatment resistance. OSM has multiple homeostatic functions with both pathogenic and protective roles. Still, its function in IBD continues to be enigmatic. The aim of this study is to evaluate protein expression of OSM and its receptor-β (OSMR) using immunohistochemical staining, along with the tight junction protein occludin and immune cell marker CD45, to understand the possible mechanisms behind its pathogenic effects in inflammatory process. METHODS This was a retrospective study conducted in pediatric patients. Patients’ clinical courses were stratified as groups: IBD (n=73) consisting of failed anti-TNF (n=19), quiescent on anti-TNF (n=36), anti-TNF naïve (n=18), and age matched non-IBD (n=29). OSM, OSMR, occludin and CD45 expression were measured by immunohistochemical staining and calculated as percent of staining over total tissue area in pre-treatment colonic tissue biopsies. The expression levels were compared among the three IBD groups and non-IBD control. RESULTS OSM and OSMR total expression (% of staining area/total tissue area) didn’t differ significantly between IBD and non-IBD patients or among IBD groups (p>0.05). When evaluating OSM/OSMR expression location, lamina propria vs epithelial, 71% IBD patients had staining in the lamina propria while the expression in non-IBD was restricted to the epithelial area with only 7% in the lamina propria (P<0.05). IBD group had significantly lower total expression of occludin at 37% compared to non-IBD at 48% but higher CD45 at 37% vs 27% (p<0.05). OSM positively and significantly (P<0.05) correlated with occludin in all study subjects (IBD or non IBD) except patients with failed antiTNF treatment (p=0.197, coefficient 0.309). In contrast correlation between OSM and CD45 was only observed in the failed antiTNF treatment group (p=0.003, coefficient 0.639), not in other IBD groups. Finally, total OSM, OSMR, and occludin expression levels were significantly lower in patients with Mayo score 3 compared to score 1 or 2. CONCLUSION OSM/OSMR expression in the epithelial area and its correlation with occludin in both IBD and non-IBD hints the physiological role of OSM in barrier function. However, the expression in the lamina propria along with increased CD45 expression in IBD indicates the pathogenic role of OSM in the inflammatory process. The lack of correlation between OSM and occludin in the antiTNF refractory patients further suggest dysfunction of OSM in IBD. Our data support both pathogenic and protective roles of OSM in IBD.