Evaluating the correlation between fecal and serum calprotectin in inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), require accurate assessment of inflammatory activity to guide treatment and monitor disease course. While fecal calprotectin (FC) is an established non-invasive biomarker of intestinal inflammation, serum calprotectin (sC) has been proposed as a more convenient systemic marker, though its relationship to FC remains unclear. We conducted a prospective observational cohort study in 426 patients with IBD (277 CD, 149 UC). Both stool and blood samples were analyzed using the QUANTA Flash® Calprotectin chemiluminescent immunoassay. Overall, the correlation between fCal and sCal was weak (Spearman’s ρ = 0.21), with substantial proportional bias and wide limits of agreement, indicating poor concordance between the two biomarkers. No significant association was observed at low or intermediate fCal concentrations, while a moderate correlation emerged only at fCal levels > 250 µg/g, although systematic bias and heteroscedasticity persisted. fCal correlated more closely with symptom-based disease activity in ulcerative colitis, whereas sCal showed only weak associations with clinical indices, particularly in Crohn’s disease. Both biomarkers demonstrated modest but significant correlations with C-Reactive Protein, reflecting overlapping but distinct inflammatory pathways. In conclusion, serum calprotectin cannot be considered a surrogate for fecal calprotectin in assessing intestinal inflammation in IBD. However, it may provide complementary information on systemic inflammatory activity at higher disease burden, while fecal calprotectin remains the gold-standard noninvasive marker of mucosal inflammation.