AIM 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.METHODS AHSG serum levels were determined in treatment-na?ve newly-diagnosed patients, 96 with ulcerative colitis(UC), 84 with Crohn’s disease (CD), 62 with diarrheapredominant 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 Ig G, anti-mannobioside carbohydrate antibodies Ig G, anti-laminariobioside carbohydrate antibodies Ig G and anti-chitobioside carbohydrate antibodies Ig A were also determined via immunonephelometry and ELISA, respectively.RESULTS 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.CONCLUSION 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. AIM 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. METHODS AHSG serum levels were determined in treatment-naïve newly-diagnosed patients , 96 with Crohn’s disease (CD), 62 with diarrheapredominant 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 Ig G, anti -mannobioside carbohydrate antibodies Ig G, anti-laminariobioside carbohydrate antibodies Ig G and anti-chitobioside carbohydrate antibodies Ig A were also determined via immunonephelometry and ELISA, respectively .RESULTS The mean ± SE of serum AHSG, f ollowing 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 coefficients: -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 <0.00 1) whilethose with at least two serological markers positive testing 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. 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.