GM-CSF Antibodies and Peripheral Treg Cells as Potential Markers of Disease Activity to Guide Therapeutic Decisions in Pediatric IBD

Abstract

Objectives: 1. To measure and compare granulocytemacrophage colony-stimulating factor (GM-CSF) antibodies and peripheral regulatory T cells (Tregs) cells as non-invasive biomarkers in active inflammatory bowel disease (IBD) and remission in pediatric IBD. 2. To determine the ability of these biomarkers to predict severity/type and choice of therapy in pediatric IBD. Methods:We hypothesized that patients with severe IBD requiring biologics will have higher circulating GM-CSF antibodies and lower Foxp3+ Tregs at baseline, with subsequent improvement in response to therapy. 28 patients were prospectively analyzed. Blood collected preand post-treatment was analyzed for GM-CSF antibodies by ELISA and Tregs by flow cytometry. Clinically, PCDAI and PUCAI were scored. Wilcoxon Rank Sum tests were used to compare baseline values between groups, and paired signed-rank tests used to compare pre-and posttreatment values.Results: Median GM-CSF antibodies trended higher (0.50 µg/mL vs. 0.37) and Tregs lower (5.23% vs. 6.71%) in the biologic cohort with no significant difference between cohorts. In response to biologics, 37% showed decrease in GM-CSF antibodies and 75% showed increase in Tregs. GM-CSF antibodies trended higher in Crohn's disease (CD) than ulcerative colitis (UC) (0.81 vs. 0.31, p=0.073). Activity indices showed significant improvement in the biologic cohort of UC patients (p=0.04). Conclusion:GM-CSF antibodies and peripheral Tregs may reflect disease activity and thereby guide IBD therapy. Although no individual biomarker could predict need for biologics, their trend favors their use in a predictive model to identify the most effective treatment strategy in pediatric IBD.