Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis
Article first published online: 28 FEB 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 11, pages 2169–2179, November 2012
How to Cite
Serada, S., Fujimoto, M., Terabe, F., Iijima, H., Shinzaki, S., Matsuzaki, S., Ohkawara, T., Nezu, R., Nakajima, S., Kobayashi, T., Plevy, S. E., Takehara, T. and Naka, T. (2012), Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis, 18: 2169–2179. doi: 10.1002/ibd.22936
- Issue published online: 15 OCT 2012
- Article first published online: 28 FEB 2012
- Manuscript Accepted: 13 FEB 2012
- Manuscript Received: 12 FEB 2012
- Grant-in-Aid for Scientific Research (C). Grant Number: 22591101
- Japanese Ministry of Education, Science, Sports, and Culture
- grant-in-aid for the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
- Grant-in-Aid from the Ministry of Health, Labour and Welfare of Japan
- ulcerative colitis;
- leucine-rich alpha-2 glycoprotein;
Reliable biomarkers for monitoring disease activity have not been clinically established in ulcerative colitis (UC). This study aimed to investigate whether levels of serum leucine-rich alpha-2 glycoprotein (LRG), identified recently as a potential disease activity marker in Crohn's disease and rheumatoid arthritis, correlate with disease activity in UC.
Serum LRG concentrations were determined by enzyme-linked immunosorbent assay (ELISA) in patients with UC and healthy controls (HC) and were evaluated for correlation with disease activity. Expression of LRG in inflamed colonic tissues from patients with UC was analyzed by western blotting and immunohistochemistry. Interleukin (IL)-6-independent induction of LRG was investigated using IL-6-deficient mice by lipopolysaccharide (LPS)-mediated acute inflammation and dextran sodium sulfate (DSS)-induced colitis.
Serum LRG concentrations were significantly elevated in active UC patients compared with patients in remission (P < 0.0001) and HC (P < 0.0001) and were correlated with disease activity in UC better than C-reactive protein (CRP). Expression of LRG was increased in inflamed colonic tissues in UC. Tumor necrosis factor alpha (TNF-α), IL-6, and IL-22, serum levels of which were elevated in patients with active UC, could induce LRG expression in COLO205 cells. Serum LRG levels were increased in IL-6-deficient mice with LPS-mediated acute inflammation and DSS-induced colitis.
Serum LRG concentrations correlate well with disease activity in UC. LRG induction is robust in inflamed colons and is likely to involve an IL-6-independent pathway. Serum LRG is thus a novel serum biomarker for monitoring disease activity in UC and is a promising surrogate for CRP. (Inflamm Bowel Dis 2012;)