Increased fecal calprotectin levels in Crohn's disease correlate with elevated serum Th1- and Th17-associated cytokines

PLoS One. 2018 Feb 21;13(2):e0193202. doi: 10.1371/journal.pone.0193202. eCollection 2018.

Abstract

Background: Patient-reported symptoms and endoscopic disease activity do not correlate well in Crohn's disease (CD). This warrants the need for reliable biomarkers to early detect active intestinal inflammation. Currently, the fecal calprotectin level is the most commonly used biomarker for inflammatory activity in CD. However, the diagnostic accuracy of the fecal calprotectin level is not fully efficacious and diagnosis may be further improved by the identification of other biomarkers for active CD. Here, we studied the association of a variety of serum disease markers with fecal calprotectin levels in CD patients.

Methods: 39 CD patients were included and subdivided into 'normal' (defined as < 200 mg/kg feces) and 'increased' (defined as > 200 mg/kg feces) fecal calprotectin level groups. Serum levels of 37 different cytokines, chemokines and markers for angiogenesis and vascular injury were quantified by an electrochemiluminescence multiplex assay (V-PLEX Human Biomarker 40-Plex Kit of Meso Scale Discovery ®). Correlations between individual biomarkers and the fecal calprotectin level were assessed using Spearman's correlation coefficient (ρ).

Results: A highly significant positive correlation was observed between the pro-inflammatory serum cytokines IFN-γ and CRP and fecal calprotectin levels (P < 0.01). Moreover, fecal calprotectin levels showed a significant positive correlation with IL-6, TNF-β, SAA and IL-17A (P < 0.05).

Conclusion: We show that a positive correlation exists between multiple serum Th1- and Th17-associated cytokines and the fecal calprotectin level. These cytokines and CRP may serve as additional biomarkers for determining disease activity and evaluating treatment response in CD. Ultimately, this may result in more efficient treatment of active disease in CD patients and prevention of complications.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology
  • Cytokines / blood*
  • Feces*
  • Female
  • Humans
  • Leukocyte L1 Antigen Complex / metabolism*
  • Male
  • Middle Aged
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology
  • Th17 Cells / metabolism*
  • Th17 Cells / pathology

Substances

  • Cytokines
  • Leukocyte L1 Antigen Complex

Grants and funding

The research position of drs. J.Z.H. von Martels is financed by the Top Institute of Food and Nutrition (TIFN) in Wageningen and the Center for Development & Innovation of the University Medical Center Groningen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.