alpha 2-Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease

作者:Manolakis Anastassios C; Christodoulidis Gregory*; Kapsoritakis Andreas N; Georgoulias Panagiotis; Tiaka Elisavet K; Oikonomou Kostas; Valotassiou Varvara J; Potamianos Spyros P
来源:World Journal of Gastroenterology, 2017, 23(3): 437-446.
DOI:10.3748/wjg.v23.i3.437

摘要

AIM To investigate the impact of inflammatory bowel disease (IBD) on alpha 2-Heremans-Schmid Glycoprotein (AHSG/fetuin A) and potential associations with disease and patient characteristics. METHODS AHSG serum levels were determined in treatment-naive 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 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. 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-TNF alpha 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.

  • 出版日期2017-1-21