title: [Alteration of the glycan profile of serum glycoproteins during the seroconversion process in hepatitis B virus-infected patients treated with antiviral therapy and its clinical significance].
abstract: OBJECTIVE
  To use a lectin microarray to study the alteration of glycan affinity profiles of serum glycoproteins during the hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) seroconversion in patients with chronic hepatitis B (CHB) following treatment with antiviral therapy,and to explore its biological significance.
  
  
  METHODS
  CHB patients were divided into the following four groups:untreated HBeAg-positive,HBeAg seroconversion after anti-HBV therapy,HBsAg loss after anti-HBV therapy,and healthy individuals (controls).Serum samples were collected from each participant,depleted of high abundance proteins and analyzed by a lectin microarray containing 50 lectins.The lectin-affinity glycan profiles of serum proteins were partially verified by lectin blotting.Between-group differences were analyzed by one-way analysis of variance,and pairwise comparisons were carried out with the Student-Newman-Keuls (SNK) method.
  
  
  RESULTS
  The results from the lectin microarray and lectin blotting assay showed significantly reduced affinity for 16 lectins in the untreated HBeAg-positive group compared to the control group (P less than 0.05);in addition,the specific glycan profiles of the untreated HBeAg-positive group included decreased terminal and core fructose,GalNAc alpha-Thr/Ser (T,Tn-antigen),GalNac alpha,terminal beta1-4,and beta-D galactose,bisecting and/or GlcNAc,mannose and Sia.However,the HBeAg seroconversion after anti-HBV therapy group showed enhanced binding of PSA,MPL and the above-mentioned 16 lectins (P less than 0.05),suggesting that the reduced serum glycoprotein glycan structures returned to normal or slightly higher than healthy levels after the therapy-induced seroconversion.Comparison of the group with HBsAg loss after anti-HBV therapy to the group with HBeAg seroconversion after anti-HBV therapy showed the binding ability of ten lectins (AAL,ACL,HAL,HPL,RCA-I,LEL,STL,PHA-E,NML and PCL) were weakened to near control levels and six lectins (VAL,LCA,GNL,PSA,MPL and JAC) were significantly strengthened (all P less than 0.05). These findings implied that the glycan containing terminal fructose, GalNacalpha, terminal beta1-4 galactose,and bisecting GlcNAc glycan structures dropped to near control levels, while the terminal beta-D-galactose residues and core fructose structure increased significantly.
  
  
  CONCLUSIONS
  The glycan structures of serum glycoproteins are closely related to HBeAg and HBsAg seroconversion in CHB patients.It is possible that a special lectin binding glycan involving the terminal beta-D-galactose residues and core fructose may act as sugar markers associated with the disappearance of serum HBsAg during anti-HBV therapy for CHB.
authors.affiliation: Department of Infectious Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Youlan
authors.initials: Y
authors.lastname: Gu
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Tang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.forename: Yinkun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D005690:Galactose; D006023:Glycoproteins / Q000097:blood*; D006513:Hepatitis B e Antigens; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D010835:Phytohemagglutinins; D011134:Polysaccharides / Q000032:analysis*
chemical_list: D000998:Antiviral Agents; D006023:Glycoproteins; D006513:Hepatitis B e Antigens; D010835:Phytohemagglutinins; D011134:Polysaccharides; C067494:erythroagglutinating phytohemagglutinin; D005690:Galactose