Serum Glycoproteome Profiles for Distinguishing Intestinal Fibrosis from Inflammation in Crohn's Disease

<div><p>Background</p><p>Reliable identification and quantitation of intestinal fibrosis in the setting of co-existing inflammation due to Crohn’s disease (CD) is difficult. We aimed to identify serum biomarkers which distinguish inflammatory from fibrostenotic phenotypes of CD using serum glycoproteome profiles.</p><p>Methods</p><p>Subjects with fibrostenotic and inflammation-predominant CD phenotypes (n = 20 per group) underwent comparison by quantitative serum glycoproteome profiles as part of a single tertiary care center cohort study. Following lectin elution, glycoproteins underwent liquid chromatography followed by tandem mass spectrometry. Identified candidate biomarkers of fibrosis were also measured by serum ELISA, a widely available technique.</p><p>Results</p><p>Five (5) glycoproteins demonstrated a ≥20% relative abundance change in ≥80% of subjects, including cartilage oligomeric matrix protein (COMP) and hepatocyte growth factor activator (HGFA). COMP (431.7±112.7 vs. 348.7±90.5 ng/mL, <i>p</i> = 0.012) and HGFA (152.7±66.5 vs. 107.1±38.7 ng/mL, <i>p</i> = 0.031) serum levels were elevated in the fibrostenotic vs. inflammatory CD groups using ELISA. Within the fibrostenotic group, intra-individual changes of candidate biomarkers revealed HGFA levels significantly declined following the resection of all diseased intestine (152.7±66.5 vs. 107.1±38.7 ng/mL, <i>p</i> = 0.015); COMP levels were unchanged. Immunohistochemical staining confirmed the presence of COMP in the submucosa and muscularis of resected fibrostenotic tissue.</p><p>Conclusions</p><p>In this biomarker discovery study, several serum glycoproteins, specifically COMP and HGFA, differ between between predominately inflammatory and fibrostenotic CD phenotypes. The development of blood-based biomarkers of fibrosis would provide an important complement to existing prognostic tools in IBD, aiding decisions on therapeutic intensity and mechanism selection, surgery, and the monitoring of future anti-fibrotic therapies for CD.</p></div

Patient characteristics.

<p>Patient characteristics.</p

COMP presence in fibrostenotic Crohn’s disease and unaffected intestine.

<p>H&E staining of fibrostenoic (panel a) demonstrating smooth muscle hypertrophy and tissue architectural changes typical of Crohn’s disease, compared to normal unaffected intestine (panel b). Immunohistochemical staining for COMP (red), with DAPI nuclear background staining (blue), reveals accumulation within the submucosa and distorted muscularis (panels c, e) compared to minimal COMP staining tissue in normal intestine (panels d,f).</p

Glycoproteins differentiating inflammatory and fibrostenotic phenotypes.

<p>Glycoproteins differentiating inflammatory and fibrostenotic phenotypes.</p

CT utilization abruptly increases at age 18 among patients with inflammatory bowel diseases in the hospital

<div><p>Objectives</p><p>Patients with inflammatory bowel disease(IBD) are frequently exposed to computed tomography (CT). Each CT exposes patients to radiation that cumulatively could increase the risk of malignancy, particularly in younger patients. We aim to study the effect of age on CT use in IBD patients seen in the Emergency Department (ED) or the hospital.</p><p>Methods</p><p>We conducted a retrospective cohort study of IBD patients identified in Truven Health Marketscan databases between 2009–2013. The main outcome was use of CT during an ED or inpatient visit. Effect of age on CT use was characterized using logistic regression accounting for important covariables.</p><p>Results</p><p>There were 66,731 patients with IBD with 144,147 ED or inpatient visits in this cohort with a diagnosis code of IBD. At first visit, 5.8% percent were below age 18. CT was utilized in 26.6% of visits. In multivariable analysis, adjusting for medications, recent surgery, and gender, patients 18–35 were more likely to undergo CT (OR 2.35, 95%CI: 2.20–2.52) compared to those <18. Examining patients only between 16 and 19, the odds of an 18 or 19-year-old undergoing CT is significantly higher than a 16 or 17-year-old (OR 1.96, 95%CI: 1.71–2.24).</p><p>Conclusions</p><p>Patients with IBD undergo CT more than a quarter of the time in the ED or inpatient setting. Pediatric providers limit radiation exposure among those <18 while adult providers are not as cautious with radiation exposure for the young adult population. Increased awareness of the risks of cumulative radiation exposure in the young adult population is needed.</p></div

Glycoproteins demonstrating change following resection of fibrostenotic disease.

<p>Glycoproteins demonstrating change following resection of fibrostenotic disease.</p

CT utilization by age among patients with IBD in the hospital or ED.

<p>Predicted probability of CT use by age demonstrates an abrupt increase at age 18 (vertical red line) for a male with Crohn’s disease (1A) or ulcerative colitis (1B) on no medications and with no recent surgery.</p

Multivariable predictors of CT use during an inpatient or ED visit with a first or second diagnosis of IBD.

<p>Multivariable predictors of CT use during an inpatient or ED visit with a first or second diagnosis of IBD.</p

Univariable predictors of CT use during an Inpatient or ED visit with a first or second diagnosis of IBD.

<p>Univariable predictors of CT use during an Inpatient or ED visit with a first or second diagnosis of IBD.</p

Correction: Corticosteroid Use and Complications in a US Inflammatory Bowel Disease Cohort

<p>Correction: Corticosteroid Use and Complications in a US Inflammatory Bowel Disease Cohort</p