Chronic inflammation and other changes are significant components of clinically fibrotic strictures in Crohn’s disease: a histological study of resected strictures clinically characterized as noninflamed

Abstract

Background Strictures related to Crohn’s disease due to fibrosis are a result of an exaggerated tissue remodelling response to inflammation, characterized by accumulation of collagen-rich extracellular matrix produced by mesenchymal cells. Objectives The objective of this study was to characterize histological changes seen in resected ‘fibrotic’ strictures to better understand individual components of intestinal stenosis. Methods We identified patients undergoing surgery for ileal Crohn’s disease secondary to symptomatic stricturing disease (Montreal B2) using the histopathology database at Queen Elizabeth Hospital in Birmingham, UK, between 2012 and 2017. Phenotypic data were recorded and resection specimens reviewed. Two independent pathologists applied the semiquantitative scoring system previously developed by us to the microscopic images. Data were analyzed using the possible maximum total score (%PMTS). Results Forty-eight patients (M = 25) were included. with median disease duration of 7 years (range 0.25–39 years); nearly two-thirds had ileocolonic distribution (L3). In this cohort, despite presurgery diagnosis of noninflamed fibrosis, chronic inflammation was noted to be a prominent component of all strictures. The histological scoring showed presence of several other prominent findings such as muscular hyperplasia and volume expansion.There was statistically significant positive correlation between chronic inflammation and fibrosis and muscular hyperplasia. Conclusion The histological features of Crohn’s disease-related strictures show multiple changes in multiple layers and not simply fibrosis. In our cohort, despite the observation prior to surgery that strictures were clinically considered fibrotic, the finding of chronic inflammation as a dominant component at a histological level in the resection is important. The findings might suggest that one of the main drivers of progressive fibrosis is the inflammatory component, which probably is never fully resolved.

Diagnostic and Predictive Value of Immune-Related Genes in Crohn’s Disease

“…Evidences have confirmed that CD is a chronic inflammatory intestinal disease, which is caused by an unrestrainable immune response against luminal bacterial antigens. The role of inflammatory cells infiltrating in maintaining an active stage is well established and most of the therapeutic strategies are aiming to block the cascade of inflammatory reaction and release of proinflammatory cytokines (14,15). In the present study, by analyzing the data for CD, non-inflammatory tissues, and normal intestinal tissues using ssGSEA, we described the landscape of immune infiltration in CD and found that the fraction of 16 immune cells was significantly different among these three kinds of tissues.…”

Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn’s disease

“…Dysregulation of immune cell transport in the intestine is an important cause of CD pathogenesis [ 29 ]. Current treatment strategies typically focus on blocking the inflammatory response cascade and pro-inflammatory cytokines [ 30 , 31 ]. In this study, we employed a variety of bioinformatics methods to analyze several datasets from the GEO database, identifying four distinct cell types that differ between CD and normal tissues: naive B cells, macrophages, plasma cells, and NK cells.…”