Association of Circulating Fibrocytes With Fibrostenotic Small Bowel Crohn’s Disease

Abstract

Background Fibrocytes are hematopoietic cells with features of mesenchymal cells found in the circulation and inflammatory sites implicated in promoting fibrosis in many fibroinflammatory diseases. However, their role(s) in the development of intestinal fibrosis is poorly understood. Here, we investigated a potential role of fibrocytes in the development of fibrosis in Crohn’s disease (CD) and sought factors that may impact their development and function. Methods Plasma and mononuclear cells were collected from patients with and without fibrostenotic CD. Fibrocytes defined as CD11b+, CD34+, and Collagen 1+ were correlated with clinical assessments of fibrosis, including evaluation using intestinal ultrasound. We measured the levels of relevant circulating molecules via Luminex and studied the effect of patient plasma proteins on fibrocyte differentiation. Results Fibrocyte numbers were increased in CD patients with stricturing Crohn’s disease compared with patients with an inflammatory phenotype (P = .0013), with strong correlation between fibrocyte numbers and acoustic radiation force impulse (ARFI), a measure of bowel elasticity on intestinal ultrasound (R = .8383, P = .0127). Fibrostenotic plasma was a more potent inducer of fibrocyte differentiation in both primary human monocytes and cell line and contained increased levels of cytokines implicated in fibrocyte differentiation compared with plasma from inflammatory patients. Interestingly, increased fibrocyte numbers at time of ultrasound were associated with escalation of medical therapy and endoscopic/surgical management of small bowel strictures at 30 months follow-up. Conclusions Circulating fibrocytes strongly correlate with fibrostenotic disease in CD, and they may serve as predictors for escalation of medical +/- surgical therapy.

Intestinal strictures in Crohn’s disease: a 2021 update

“… 20 It was assumed that the unique plasma protein profile from fibrostenotic CD patients might predispose human peripheral blood mononuclear cells to transform into fibrocyte-like cells. 20 Besides, within a 30-month follow-up, the increment of circulating fibrocytes was correlated with the subsequent escalation of medical therapy, endoscopic dilation, or surgery. These results suggest that circulating fibrocytes might serve as a disease predictor and provide a new route toward intestinal fibrostenosis.…”

“…These results suggest that circulating fibrocytes might serve as a disease predictor and provide a new route toward intestinal fibrostenosis. 20 …”

Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn’s disease: image processing and analysis study

“…

Crohn's disease (CD), a form of idiopathic inflammatory bowel disease (IBD), has an estimated annual incidence of 3.1 to 20.2 per 100,000, and a prevalence of 201 per 100,000 in North America [1,2]. Based on its clinical behavior, CD is classified as B1 (non-stricturing, non-penetrating), B2 (stricturing) and B3 (penetrating) [3][4][5]. While most CD patients initially present as B1, they can have more than one phenotype, and clinical behavior may change over time [4]; i.e., a patient with B1 phenotype may develop strictures and or fistula during the disease course and subsequently be re-classified as having a B2 or B3 phenotype [6,7].

…”

“…Stricture is the most common indication for surgery in CD [8].The progression of fibrosis and eventual stricture formation is a significant disease burden requiring escalation of medical treatment or surgical intervention in CD. Although many factors, such as genetic, epigenetic, serological, clinical, environmental, and endoscopic factors are postulated to portend an increased risk for fibrosis progression, its pathogenesis is relatively poorly understood [5,9,10]. Moreover, most of the pathological studies using formalin-fixed paraffin-embedded (FFPE) tissue are limited to morphological evaluation on routine hematoxylin and eosin (H&E)…”

“…Previous studies have suggested that inflammation and mesenchymal components, at least in part, play a role in the fibrogenesis of CD [ 5 , 9 , 12 , 13 ]. Fecal calprotectin is a well-established non-invasive measure of inflammation and disease activity in IBD [ 14 , 15 ].…”