Fecal biomarkers in inflammatory bowel diseases: calprotectin versus lipocalin-2 - a comparative study.

BACKGROUND AND AIMS Fecal biomarkers, particularly calprotectin (FCAL), have become important diagnostic and monitoring tools in inflammatory bowel diseases (IBD). As FCAL is mainly produced by neutrophils, we hypothesized that fecal lipocalin-2 (FLCN2), also expressed by intestinal epithelial cells (IEC), could be beneficial in specific clinical situations. METHODS We compared clinical and endoscopic activity-related correlations between FCAL and FLCN2, assayed from the same sample, in a cohort of 132 patients (72 CD) and 40 controls. A detailed analysis of cellular origins was done by confocal microscopy and flow-cytometry. To evaluate the potential to detect low-grade inflammation, we studied fecal and tissue concentrations in a cohort with clinical, endoscopic and histological remission. RESULTS There was an excellent correlation between FCAL and FLCN2 (rS = 0.87, p <0.001) and a comparable sensitivity and specificity to predict clinical and endoscopic disease activity, with optimal thresholds for endoscopic activity of 73.4 and 1.98 µg/g in ulcerative colitis (UC) and 78.4 and 0.56 µg/g in Crohn's disease (CD) for FCAL and FLCN2, respectively. Strong co-expression of both proteins was observed in granulocytes and macrophages. IECs expressed LCN2 but not CAL. In our IBD cohort in deep remission neither FCAL nor FLCN2 was different from controls, yet mucosal LCN2 but not CAL expressions remained elevated in the rectum of UC and the ileum of CD patients. CONCLUSION This study corroborates the diagnostic equivalence of FLCN2 and FCAL in IBD. In remission, persistent mucosal overexpression renders LCN2 an attractive candidate for molecular inflammation warranting further investigation.