Serum levels of NLRC4 and MCP-2/CCL8 in patients with active Crohn's disease.

Kader Irak,Gulsen Sener,Sami Cifci,Mehmet Bayram,David M Ojcius

doi:10.1371/journal.pone.0260034

Abstract

Crohn's disease (CD) is characterized by malfunction of immune-regulatory mechanisms with disturbed intestinal mucosal homeostasis and increased activation of mucosal immune cells, leading to abnormal secretion of numerous pro- and anti-inflammatory mediators. MCP2/CCL8 is produced by intestinal epithelial cells and macrophages, and is a critical regulator of mucosal inflammation. NLRC4 is expressed in phagocytes and intestinal epithelial cells and is involved in intestinal homeostasis and host defense. However, no study to date has assessed the circulating levels of NLRC4 and MCP2/CCL8 in patients with CD. The study was aimed to investigate the serum levels of MCP2/CCL8 and NLRC4 in patients with active CD. Sixty-nine patients with active CD and 60 healthy participants were included in the study. Serum levels of NLRC4 and MCP2/CCL8 were determined using an enzyme-linked immunosorbent assay. The median serum NLRC4 levels were lower in the patient group than in the controls (71.02 (range, 46.59-85.51) pg/mL vs. 99.43 (range 83.52-137.79) pg/mL) (P < 0.001). The median serum levels of MCP2/CCL8 were decreased in patients with CD (28.68 (range, 20.16-46.0) pg/mL) compared with the controls (59.96 (range, 40.22-105.59) pg/mL) (P < 0.001). Cut-off points of NLRC4 (<81 pg/mL) and MCP2/CCL8 (<40 pg/mL) showed high sensitivity and specificity for identifying active CD. In conclusion, this is the first study to examine circulating levels of MCP2/CCL8 and NLRC4 in patients with active CD. Our results suggest that serum NLRC4 and MCP2/CCL8 levels may be involved in the pathogenesis of CD and may have a protective effect on intestinal homeostasis and inflammation. Serum levels of MCP2/CCL8 and NLRC4 could be used as a diagnostic tool and therapeutic target for CD.

Highlights

Crohn’s disease (CD) is a chronic inflammatory condition characterized by transmural, remitting and relapsing, focal inflammation involving different sites of the gastrointestinal tract, from the mouth to the anus [1]
NLR-caspase activation and recruitment domain-containing protein 4 (NLRC4) and monocyte chemoattractant protein 2 (MCP2)/CCL8 levels were found to be negatively correlated with age, CRP, red blood cell distribution width (RDW), nucleotide-binding and oligomerization domain-like receptor family (NLR), platelet-to-lymphocyte ratio (PLR), and positively correlated with platelet count, white blood cell count (WBC), neutrophil count, and lymphocyte count (p
We demonstrated significantly lower serum NLRC4 levels among patients with active CD than in healthy individuals

Summary

Introduction

Crohn’s disease (CD) is a chronic inflammatory condition characterized by transmural, remitting and relapsing, focal inflammation involving different sites of the gastrointestinal tract, from the mouth to the anus [1]. The epidemiology of the disorder, traditionally regarded as a condition of developed countries, is changing around the world at the beginning of the 21st century with the rapid increase in the incidence of newly industrialized countries in Asia, South America, and Africa [2]. Rapid changes in CD epidemiology have led to a global. Levels of NLRC4 and MCP-2/CCL8 & active Crohn’s disease

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