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

Abstract

BackgroundAntimicrobial peptide expression is associated with disease activity in inflammatory bowel disease (IBD) patients. IBD patients have abnormal expression of elafin, a human elastasespecific protease inhibitor and antimicrobial peptide. We determined elafin expression in blood, intestine, and mesenteric fat of IBD and non-IBD patients. MethodsSerum 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. ResultsHigh 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.

Artificial Intelligence Enhances Studies on Inflammatory Bowel Disease

“…The authors concluded the baseline laboratory parameters, patient demographic characteristics, and disease location as the most robust predictors ( Reddy et al, 2019 ). A recent study indicated that the accuracy of elafin for revealing strictures in patients with CD was increased with a two-class decision forest algorithm ( Wang et al, 2020 ). These studies showed the application of longitudinal data in predicting disease progression, which was followed by the use of ML methods to predict the prognosis of disease for avoiding over-treatment or delayed treatment.…”

Proteins as Targets in Anti-Schistosomal Drug Discovery and Vaccine Development

“…A study by Becker and co-workers reported that a serine protease inhibitor, elafin, may be a novel substrate for SmCE; it would inhibit the action of SmCE during the cercarial stage of the parasite and act as an effective barrier against infection by preventing successful penetration of the cercariae [ 5 ]. Elafin is a low molecular weight human protein that is produced naturally in the skin, lung and breast, protecting these tissues from destruction by the immune system [ 62 ]. This protein plays an important role in wound healing in the dermal immune response in humans, while also acting as an antimicrobial agent against other pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus .…”

Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

“…Its level is progressively decreased when these patients develop diabetic nephropathy, suggesting its involvement in diabetes. Elafin is a small (6 kDa) human elastase-specific protease inhibitor and antimicrobial peptide primarily expressed in immune cells, intestinal tract, vagina, lungs, and skin 9 , 10 . Circulating elafin levels are positively correlated with inflammatory bowel disease and graft-versus-host disease 10 , 11 .…”

“…Elafin is a small (6 kDa) human elastase-specific protease inhibitor and antimicrobial peptide primarily expressed in immune cells, intestinal tract, vagina, lungs, and skin 9 , 10 . Circulating elafin levels are positively correlated with inflammatory bowel disease and graft-versus-host disease 10 , 11 . Elafin expression is also increased in human atherosclerotic coronary arteries and mesenteric fat in stricturing Crohn’s disease patients 10 , 12 .…”

“…Circulating elafin levels are positively correlated with inflammatory bowel disease and graft-versus-host disease 10 , 11 . Elafin expression is also increased in human atherosclerotic coronary arteries and mesenteric fat in stricturing Crohn’s disease patients 10 , 12 . However, the circulating levels of elafin in patients with T2DM are unknown.…”