Recruitment of activated neutrophils correlates with disease severity in adult Crohn’s disease

Abstract

Summary Neutrophils are detected in inflamed colon in Crohn’s disease (CD). However, whether the frequency and/or activation of circulating or gut tissue neutrophils correlate with endoscopic severity remains to be investigated. A cohort of 73 CD patients was prospectively enrolled according to endoscopic severity and treatment history. Individuals with active disease were stratified using the Montreal classification. Harvey–Bradshaw Index (HBI) and Simple Endoscopic Score for Crohn’s Disease (SES‐CD) were performed at the time of ileocolonoscopy. Frequency of neutrophils and their expression of CD66b and CD64 were assessed in paired blood and colonic biopsies using flow cytometry. The percentage of neutrophils increased in inflamed colon and correlated with SES‐CD in the entire cohort of patients examined, as well as in the subgroup with inflammatory (B1) active disease. SES‐CD further correlated with neutrophil CD66b expression in mucosa but not blood and, conversely, with neutrophil CD64 expression in blood but not mucosa. However, the evaluation of neutrophil activation in mucosa when compared to blood reflected disease activity more clearly. Finally, a neutrophil activation power index (CD66b in mucosa X CD64 in blood) that correlated with SES‐CD discriminated between patients with mild and severe disease. In conclusion, the frequency and activation of colonic neutrophils correlated with SES‐CD, highlighting that mucosal neutrophils are associated with disease severity in CD.

Identification of Immune Cell Landscape and Construction of a Novel Diagnostic Nomogram for Crohn’s Disease

“…These results suggested that neutrophils are essential for CD progression; however, whether its role is pathological or beneficial remains controversial. Recently, singlecell analysis revealed that neutrophils recruitment and activation was correlated with clinical disease severity in CD (Therrien et al, 2019). However, Zhou et al (2018) demonstrated that the CD177 + neutrophils showed a protective effect in IBD through increased anti-bacterial activity and IL-22 production.…”

Neutrophil Extracellular Traps in Inflammatory Bowel Disease: Pathogenic Mechanisms and Clinical Translation

“…16 They also released a host of proteases, proinflammatory cytokines and mediators such as IL-8, TNF-a, and leukotriene B 4 that damage the epithelial barrier and recruit monocytes and more neutrophils to the gut. 17,18 Neutrophil infiltration correlates with disease activity in IBD [19][20][21][22][23] and is a widely used and reliable component of UC disease scoring systems. 24 Calprotectin (s100A8/9), the most widely used biomarker in IBD, constitutes up to 60% of neutrophil cytosolic proteins.…”

Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples

“…Notably, the dysregulated transformation of infiltrating monocytes to pro-inflammatory cytokine producing cells, as well as altered macrophages with ability to induce T H 17 differentiation in patients with IBD, suggest the relevance of innate immune cells as triggers of pathogenic intestinal inflammation [79,81]. On the other hand, the significant recruitment of neutrophils is well-described in IBD patients, but their role is contradictory, as some reports suggest their advantageous role during intestinal inflammation, while others described tissue damaging effects [82,83].…”