Dataset Information

High circulating elafin levels are associated with Crohn's disease-associated intestinal strictures.

ABSTRACT: BACKGROUND:Antimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients. METHODS:Serum samples from normal and IBD patients were collected from two UCLA cohorts. Surgical resection samples of human colonic and mesenteric fat tissues from IBD and non-IBD (colon cancer) patients were collected from Cedars-Sinai Medical Center. RESULTS:High serum elafin levels were associated with a significantly elevated risk of intestinal stricture in Crohn's disease (CD) patients. Microsoft Azure Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlations with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index), but not endoscopic disease activity (Mayo Endoscopic Subscore and Simple Endoscopic Index for CD) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels. Colonic elafin mRNA and protein expression were not associated with clinical disease activity and histological injury in IBD patients, but stricturing CD patients had lower colonic elafin expression than non-stricturing CD patients. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA and protein expression, which may contribute to high circulating elafin levels. Human mesenteric fat adipocytes secrete elafin protein. CONCLUSIONS:High circulating elafin levels are associated with the presence of stricture in CD patients. Serum elafin levels may help identify intestinal strictures in CD patients.

SUBMITTER: Wang J

PROVIDER: S-EPMC7156098 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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High circulating elafin levels are associated with Crohn's disease-associated intestinal strictures.

Wang Jiani J Ortiz Christina C Fontenot Lindsey L Xie Ying Y Ho Wendy W Mattai S Anjani SA Shih David Q DQ Koon Hon Wai HW

PloS one 20200414 4

<h4>Background</h4>Antimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients.<h4>Methods</h4>Serum samples from normal and IBD patients were collected from two UCLA cohorts. Surgical resection samples of human colonic and ...[more]

PMID: 32287314

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Project description:AimTo develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease (CD).MethodsChronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9) and TIMP1 mRNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry.ResultsIntestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells (SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The mRNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time.ConclusionThese findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.

Project description:ObjectivesIdentifying inflammation- or fibrosis-predominant strictures in Crohn's disease (CD) is crucial for treatment strategies. We evaluated the additive value of magnetisation transfer (MT) to conventional MRI for differentiating CD strictures using surgical histopathology as a reference standard.MethodsTwenty-eight consecutive CD patients who underwent MRI preoperatively were recruited. MRI parameters included T2-weighted imaging (T2WI) hyperintensity, bowel wall thickness, enhancement pattern changes over time, enhancement pattern and gain ratio in dynamic contrast-enhanced phases, and MT ratio. Correlation analysis was performed using Spearman's rank test. Receiver operating characteristic curve analysis and Cohen's κ were used. A model with combined MRI variables characterising intestinal strictures was proposed and validated in 14 additional CD patients.ResultsSignificant correlations with histological inflammation scores were shown for wall thickness (r = 0.361, p = 0.001) and T2WI hyperintensity (r = 0.396, p < 0.001), whereas histological fibrosis scores were significantly correlated with MT ratio (r = 0.681, p < 0.001) and wall thickness (r = 0.461, p < 0.001). T2WI hyperintensity could differentiate mild from moderate-to-severe inflammation with a sensitivity of 0.871 and a specificity of 0.800. MT ratio could discriminate mild from moderate-to-severe fibrosis with a sensitivity and a specificity of 0.913 and 0.923, respectively. Combining MT ratio and T2WI hyperintensity, the MRI classification moderately agreed with the pathological stricture classification (p < 0.01, κ = 0.549). In the validation set, the diagnostic accuracy of T2WI hyperintensity and MT ratio were 86% and 89%, with good agreement between MRI and histopathological classification (p < 0.01, κ = 0.665).ConclusionsMT ratio combined with conventional MRI improves the differentiation of fibrotic from inflammatory components of small-bowel strictures in CD patients.Key points• MT ratio from magnetisation transfer imaging combined with T2WI from conventional MRI can simultaneously characterise bowel fibrosis and inflammation in adult Crohn's disease.

Dataset Information

High circulating elafin levels are associated with Crohn's disease-associated intestinal strictures.

Publications

High circulating elafin levels are associated with Crohn's disease-associated intestinal strictures.

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