Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2017; 23(3): 437-446
Published online Jan 21, 2017. doi: 10.3748/wjg.v23.i3.437
α2-Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease
Anastassios C Manolakis, Gregory Christodoulidis, Andreas N Kapsoritakis, Panagiotis Georgoulias, Elisavet K Tiaka, Kostas Oikonomou, Varvara J Valotassiou, Spyros P Potamianos
Anastassios C Manolakis, Andreas N Kapsoritakis, Elisavet K Tiaka, Kostas Oikonomou, Spyros P Potamianos, Department of Gastroenterology, University of Thessaly, School of Medicine, 41110 Larissa, Greece
Gregory Christodoulidis, Department of Surgery, University of Thessaly, School of Medicine, 41110 Larissa, Greece
Panagiotis Georgoulias, Varvara J Valotassiou, Laboratory of Nuclear Medicine, University of Thessaly, School of Medicine, 41110 Larissa, Greece
Author contributions: Manolakis AC, Christodoulidis G, Kapsoritakis AN, Georgoulias P and Potamianos SP designed the research. Manolakis AC, Christodoulidis G, Tiaka EK, Oikonomou K, Valotassiou VJ performed the research; Georgoulias P and Valotassiou VJ contributed reagents/analytic tools and carried out assays; Manolakis AC and Tiaka EK analyzed the data; Manolakis AC, Christodoulidis G, Kapsoritakis AN and Potamianos SP wrote the paper.
Supported by the Hellenic Society of Gastroenterology, No. 5496.
Institutional review board statement: The study was reviewed and approved by the University of Thessaly Medical School Ethics Committee.
Informed consent statement: Informed consent was obtained from all study participants, along with a verbal permission for the use of the acquired samples for scientific research.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Gregory Christodoulidis, MD, PhD, Department of Surgery, University of Thessaly, School of Medicine, Filellinon, 41110 Mezourlo, Larissa, Greece.
Telephone: +30-241-3502727 Fax: +30-241-3502727
Received: September 22, 2016
Peer-review started: September 23, 2016
First decision: November 9, 2016
Revised: November 25, 2016
Accepted: December 21, 2016
Article in press: December 21, 2016
Published online: January 21, 2017

To investigate the impact of inflammatory bowel disease (IBD) on α2-Heremans-Schmid Glycoprotein (AHSG/fetuin A) and potential associations with disease and patient characteristics.


AHSG serum levels were determined in treatment-naïve newly-diagnosed patients, 96 with ulcerative colitis (UC), 84 with Crohn's disease (CD), 62 with diarrhea-predominant or mixed irritable bowel syndrome (IBS, D- and M- types) and 180 healthy controls (HC), by an enzyme linked immunosorbent assay (ELISA). All patients were followed for a minimum period of 3 years at the Gastroenterology Department of the University Hospital of Larissa, Greece. C-reactive protein (CRP), anti-glycan antibodies, anti-Saccharomyces cerevisiae mannan antibodies IgG, anti-mannobioside carbohydrate antibodies IgG, anti-laminariobioside carbohydrate antibodies IgG and anti-chitobioside carbohydrate antibodies IgA were also determined via immunonephelometry and ELISA, respectively.


The mean ± SE of serum AHSG, following adjustment for confounders, was 0.32 ± 0.02 g/L in IBD, 0.32 ± 0.03 g/L in CD and 0.34 ± 0.03 g/L in UC patients, significantly lower than in IBS patients (0.7 ± 0.018 g/L) and HC (0.71 ± 0.02 g/L) (P < 0.0001, in all cases). AHSG levels were comparable between the CD and UC groups. Based on AHSG levels IBD patients could be distinguished from HC with about 90% sensitivity and specificity. Further adjusted analysis verified the inverse association between AHSG and penetrating, as well as stricturing CD (partial correlation coefficient: -0.45 and -0.33, respectively) (P < 0.05). After adjusting for confounding factors, inverse correlations between AHSG and CRP and the need for anti-TNFα therapy or surgery, were found (partial correlation coefficients: -0.31, -0.33, -0.41, respectively, P < 0.05, in all cases). Finally, IBD individuals who were seropositive, for at least one marker, had AHSG levels falling within the two lower quartiles (OR = 2.86, 95%CI: 1.5-5.44, P < 0.001) while those with at least two serological markers positive exhibited AHSG concentrations within the lowest quartile (OR = 5.03, 95%CI: 2.07-12.21, P < 0.001), after adjusting for age, sex and smoking.


AHSG can be used to distinguish between IBD and IBS patients or HC while at the same time "predicting" complicated disease behavior, need for therapy escalation and surgery. Moreover, AHSG may offer new insights into the pathogenesis of IBD, since it is involved in key processes.

Keywords: Inflammatory bowel disease, Irritable bowel syndrome, Fetuin A

Core tip: α2-Heremans-Schmid Glycoprotein (AHSG/fetuin A) a multi-task negative acute-phase protein is downregulated in patients with inflammatory bowel disease (IBD). Based on this significant decrease a discrimination between IBD patients with either Crohn's disease or ulcerative colitis and those with irritable bowel syndrome or healthy controls can be made. A more robust AHSG decrease correlates well with and predicts complicated disease behavior, need for biological therapy and surgery, within three years from diagnosis. These associations are supported by additional links between AHSG and acute-phase markers i.e., C-reactive protein or serological markers linked to IBD course i.e., anti-glycan antibodies.