Published online Jan 21, 2017. doi: 10.3748/wjg.v23.i3.437
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.
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.