Multivariate analysis identifies biomarkers of intestinal inflammation (47.10)

Abstract

Abstract Few predictive indicators are available for diagnosis of the chronic intestinal inflammation that characterizes inflammatory bowel disease (IBD). Identification of predictive serum biomarkers may allow for therapeutic intervention prior to disease onset in individuals bearing IBD susceptibility genes. Discriminatory multivariate modeling of 23 cytokines (plus chlorotyrosine [CT] and nitrotyrosine [NT], protein adducts from reactive oxygen and nitrogen species) in serum and tissue from two murine models of colitis was performed to identify disease- associated biomarkers. Citrobacter rodentium infection of C57BL/6J mice and Helicobacter-dependent spontaneous colitis in TLR4 x IL10 deficient mice were used as the acute and chronic colitis models. A subset of serum factors identified in the acute colitis model (NT, G-CSF, KC, IL-12/23p40 and IL-17) was also influential in the serum from mice with chronic disease. Surprisingly, the most influential acute tissue factors (11 total) were also influential in chronic tissue (15 total), and were dominated by Th17- and neutrophil-associated factors. Additionally, multivariate models generated from the influential serum or tissue factors predicted the severity of histological colonic lesions. This study has therefore identified neutrophil and Th17 associated factors in serum as predictive biomarkers of intestinal inflammation, in agreement with the presence of neutrophils and Th17 cells in the inflamed colonic tissue of patients with IBD.