Increased PECAM-1 Predicts Increased Risk for Flare in Patients With IBD

Abstract

Introduction: Predicting risk of flare-ups for patients with inflammatory bowel disease (IBD) is difficult. Changes in epithelial permeability may be an early event leading to flares in IBD. Particularly, cell adhesion molecules (CAM) are important in regulating the migration of leukocytes into the gut. We aimed to identify specific biomarkers in the colonic mucosa related to epithelial cell tight junctions that may predict the risk of relapse in a group of patients with clinically inactive inflammatory bowel disease. Methods: We identified patients with clinically inactive IBD, defined as baseline stool frequency without blood and no abdominal pain, who underwent elective colonoscopy at our VA Medical Center. Followup at 6, 12, and 24 months were reviewed to assess whether patients had relapsed or remained in remission. Relapse was defined as an increase in disease activity (i.e., increased number of stools, presence of blood, and/or abdominal pain) that the treating physician deemed as a relapse and required a change in the medication regimen. Tissue samples obtained from each patient at baseline were evaluated for gene expression by real time PCR using RT2 Profiler Human Tight Junction PCR Array (Qiagen). Results: 40 patients (23 UC, 16 Crohn's, 1 indeterminate colitis) underwent colonoscopy with tissue sampling while in clinical remission. All patients had colonic involvement of their disease; average age at enrollment 59.2 years, 88% male, 88% white, average disease duration 18 years. At 6 months from the index colonoscopy, 8 patients had experienced a flare (20%), 9 by 12 months (23%), and 11 by 24 months (28%). Preliminary analysis of 84 candidate genes was evaluated in 6 patients who experienced a flare and 6 who remained in remission. We found platelet endothelial cell adhesion molecule-1 (PECAM1) to be elevated 2.8-fold in biopsies from our patients who subsequently flared as compared to those who did not (p=0.023). Conclusion: Increased expression of PECAM1 may be an early event precipitating active inflammation in patients with IBD, particularly in UC. Looking for PECAM1 in biopsy specimens of IBD patients in clinical remission may be helpful in predicting which patients are at increased risk of flare. This may be useful in facilitating the individualization of maintenance therapy.