title: Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis.
abstract: OBJECTIVE
  Although several noninvasive and easily accessible biomarkers for inflammatory bowel disease [IBD] are available, their sensitivity and specificity are not adequate to be used as single markers and do not overrule the need for endoscopic evaluation. We previously reported that serum leucine-rich alpha-2 glycoprotein [LRG] was a novel biomarker for rheumatoid arthritis and IBD. We herein investigated whether LRG could indicate endoscopic activity in patients with ulcerative colitis [UC].
  
  
  METHODS
  Serum LRG concentrations were determined by enzyme-linked immunosorbent assay [ELISA] in consecutive 129 patients with UC in two tertiary care hospitals, and associations of LRG with clinical and endoscopic activities were evaluated. Clinical activity index [CAI] < 6 was defined as clinical remission, and mucosal healing [MH] and complete mucosal healing were defined as Matts' endoscopic grades of 1 or 2 and grade of 1, respectively.
  
  
  RESULTS
  Serum LRG levels were significantly increased and correlated with clinical and endoscopic activities in patients with UC. LRG levels were associated with both clinical and endoscopic activities even in patients with normal serum C-reactive protein [CRP] levels. Furthermore, LRG levels were significantly lower in patients with complete MH and deep remission. Serial measurements of LRG levels in a subset of patients demonstrated that LRG was significantly elevated during the endoscopically active stage compared with that during the MH stage.
  
  
  CONCLUSIONS
  Serum LRG is a novel biomarker for detecting MH during disease course in patients with UC and a surrogate marker of endoscopic inflammation in patients with normal CRP levels.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinta
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Research and Development, EIDIA Co. Ltd, Tokyo, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Arai
authors.affiliation: Department of Research and Development, EIDIA Co. Ltd, Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koyama
authors.affiliation: Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan tnaka@nibiohn.go.jp.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000473:pathology; D016099:Endoscopy, Gastrointestinal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; C015246:LRG1 protein, human
keywords: Biomarker; C-reactive protein; leucine-rich alpha-2 glycoprotein; mucosal healing