title: Serum Glycoproteome Profiles for Distinguishing Intestinal Fibrosis from Inflammation in Crohn's Disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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, p = 0.012) and HGFA (152.7±66.5 vs. 107.1±38.7 ng/mL, p = 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, p = 0.015); COMP levels were unchanged. Immunohistochemical staining confirmed the presence of COMP in the submucosa and muscularis of resected fibrostenotic tissue.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Stidham
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, MI, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, United States of America.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, MI, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Lubman
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Peter D R
authors.initials: PD
authors.lastname: Higgins
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D002853:Chromatography, Liquid; D003424:Crohn Disease / Q000175:diagnosis*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000175:diagnosis*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D006023:Glycoproteins