Research Article: Increased fecal calprotectin levels in Crohn’s disease correlate with elevated serum Th1- and Th17-associated cytokines

Date Published: February 21, 2018

Publisher: Public Library of Science

Author(s): Arno R. Bourgonje, Julius Z. H. von Martels, Paul de Vos, Klaas Nico Faber, Gerard Dijkstra, John Green.

http://doi.org/10.1371/journal.pone.0193202

Abstract

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.

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).

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). 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.

Partial Text

Crohn’s disease (CD) is a chronic inflammatory disease that mainly affects the gastro-intestinal tract and is characterized by an inappropriate and ongoing immune response. [1] Most patients suffer from a relapse-remitting disease course that is difficult to predict. [2,3] Predicting the disease course is hampered by the poor availability of adequate disease biomarkers or symptoms that forecast a flare of inflammation. Longstanding sub-clinical disease activity increases the risk of various severe complications, such as stricturing or penetrating disease (i.e. fistula or abscess formation). [4] Appropriate and prompt treatment of the inflammatory activity lowers the risk of these severe complications, and thus prevents future surgical interventions.

Characteristics of the study population are presented in Table 1. Patients with a ‘normal’ fecal calprotectin level (n = 22) had a mean age of 40.5 ± 2.4 years and consisted of 5 males (22.7%) and 17 females (77.3%). Patients with an increased level of fecal calprotectin (n = 17) had a mean age of 39.7 ± 3.4 years and consisted of 5 males (29.4%) and 12 females (70.6%). Patients with increased fecal calprotectin levels had significantly higher C-reactive protein (CRP) levels (P < 0.01) and higher erythrocyte sedimentation rates (ESR) (P < 0.05) as compared to patients with fecal calprotectin levels in the normal range. No significant differences between groups were observed for disease location, medication use, smoking habits, surgery history and standard laboratory parameters. In this study, we show that increased fecal calprotectin levels—a broadly applied marker for the assessment of disease activity in CD patients—highly significantly correlate with elevated serum IFN-γ and CRP levels. Moreover, significant correlations were observed between serum levels of IL-6, IL-17A, TNF-β and SAA and fecal calprotectin levels. These findings indicate that identification of biomarker profiles might serve as an additional approach to determine inflammatory disease activity in CD patients.   Source: http://doi.org/10.1371/journal.pone.0193202

 

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