Ileal Calprotectin Levels Predict Colon Endoscopic Activity in Patients with Inflammatory Bowel Disease

Abstract

Purpose: Calprotectin is a calcium-binding protein found in the cytosol of neutrophils; it is elevated in fecal specimens of patients with colonic inflammation such as those with Crohn's disease (CD) or Ulcerative Colitis (UC). Fecal calprotectin correlates with endoscopic severity and histologic inflammation in the colon. The goal of this study was to determine if ileal calprotectin more accurately predicts endoscopic disease activity in patients with ileal involvement of their IBD. Methods: Subjects diagnosed with IBD undergoing colonoscopy were enrolled. Samples for calprotectin were aspirated from the terminal ileum and colon. Levels were analyzed using Genova Diagnostics ELISA. Biopsies were taken from the terminal ileum and colon. Clinical disease activity was measured via Harvey Bradshaw Index (CD) and Mayo score (UC); endoscopic activity index (EAI) was measured via Mayo score. This study was approved by the Weill Cornell Medical College IRB; all patients gave informed consent Results: 15 patients were included in this study: 13 had CD, 2 had UC, and 1 had indeterminate colitis. Median age was 34, disease duration 5.5 years, and 60% of patients were male. Ileitis was present on biopsy in 27% of patients. Ileal endoscopic scores were normal in 53% of patients, mild in 33%, and moderate/severe in 13%. Colon endoscopic scores were normal in 47%, mild in 27%, and moderate/severe in 27%. Ileal and colonic calprotectin levels strongly correlated with colon EAI (r = 0.76, P= 0.001 and r = 0.74, P= 0.002, respectively). Using linear regression analysis, ileal calprotectin had a significant association with increasing colon EAI (P= 0.05) that appeared to be independent of age, gender, and disease duration (P= 0.07). Ileal and colonic calprotectin levels > 50μg/mL were associated with abnormal colonic endoscopic activity (P= 0.01 and P= 0.003, respectively). Receiver operating characteristic (ROC) analysis demonstrated that levels > 50μg/mL were predictive of abnormal colon EAI for ileal calprotectin (sensitivity 63%, specificity 100%, ROC AUC 0.81) and colonic calprotectin (sensitivity 100%, specificity 71%, ROC AUC 0.86). No associations were observed between calprotectin levels and ileal endoscopic activity or symptom scores. Conclusion: Ileal calprotectin did not predict ileal endoscopic disease. However both ileal and colonic calprotectin levels were predictive of abnormal colonic endoscopic disease activity. This may reflect that terminal ileal aspirates could be colonic in origin and thus be reflective of a backwash of colonic contents. Further studies investigating the role of ileal calprotectin in patients with more extensive ileal disease are warranted.Table: Patient Characteristics.Table: Endoscopic Findings.