title: α2-Heremans-schmid glycoprotein (fetuin A) downregulation and its utility in inflammatory bowel disease.
abstract: OBJECTIVE
  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 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 cerevisiaemannan antibodies IgG, anti-mannobioside carbohydrate antibodies IgG, anti-laminariobioside carbohydrate antibodies IgG and anti-chitobioside carbohydrate antibodies IgA were also determinedviaimmunonephelometry 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Anastassios C
authors.initials: AC
authors.lastname: Manolakis
authors.affiliation: 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.
authors.forename: Gregory
authors.initials: G
authors.lastname: Christodoulidis
authors.affiliation: 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.
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Kapsoritakis
authors.affiliation: 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.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Georgoulias
authors.affiliation: 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.
authors.forename: Elisavet K
authors.initials: EK
authors.lastname: Tiaka
authors.affiliation: 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.
authors.forename: Kostas
authors.initials: K
authors.lastname: Oikonomou
authors.affiliation: 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.
authors.forename: Varvara J
authors.initials: VJ
authors.lastname: Valotassiou
authors.affiliation: 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.
authors.forename: Spyros P
authors.initials: SP
authors.lastname: Potamianos
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003093:Colitis, Ulcerative / Q000097:blood*; D003424:Crohn Disease / Q000097:blood*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006115:Greece; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D043183:Irritable Bowel Syndrome / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis*
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein
keywords: Fetuin A; Inflammatory bowel disease; Irritable bowel syndrome