title: Aberrant serum immunoglobulin G glycosylation in chronic hepatitis B is associated with histological liver damage and reversible by antiviral therapy.
abstract: BACKGROUND
  Aberrant serum immunoglobulin G (IgG) glycosylation and its immunomodulatory effect are rarely addressed in chronic hepatitis B virus (HBV) infection.
  
  
  METHODS
  Serum IgG-Fc glycosylation profiles in 76 patients with HBV-related liver cirrhosis and 115 patients with chronic hepatitis B (CHB) before and after 48 weeks of anti-HBV nucleos(t)ide analogue treatment were analyzed using high-throughput liquid chromatography-mass spectrometry and were compared to profiles in 108 healthy controls.
  
  
  RESULTS
  The level of aberrant serum IgG-Fc glycosylation ,: particularly galactose deficiency, was higher in patients with CHB and those with cirrhosis (P < .001 for both) than in healthy controls. IgG galactose deficiency was correlated with the severity of liver necroinflammation and fibrosis in CHB. Multivariate logistic regression analyses showed that the IgG-Fc glycoform with fucosylation and fully galactosylation was an independent factor for a total Knodell necroinflammation score of ≥ 7 (odds ratio, 0.74; 95% confidence interval, .56-.97) and an Ishak fibrosis score of ≥ 3 (odds ratio, 0.69; 95% confidence interval, .49-.97). Administration of antiviral therapy for 48 weeks reversed aberrant IgG-Fc glycosylation in patients with CHB from week 12 onward but did not reverse glycosylation in patients with cirrhosis. Attenuated IgG opsonization in patients with CHB, which was correlated with aberrant Fc-glycosylation, was reversed after treatment as well.
  
  
  CONCLUSIONS
  Aberrant serum IgG-Fc glycosylation in CHB, which is highly associated with histological liver damage, affects IgG opsonizing activity and can be reversed by antiviral therapy.
authors.affiliation: Department of Internal Medicine.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Department of Internal Medicine.
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University Medical College.
authors.forename: Jia-Huei
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Liu
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Su
authors.affiliation: Department of Internal Medicine.
authors.forename: I-Chin
authors.initials: IC
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine.
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Li
authors.affiliation: Department of Pathology, National Cheng Kung University Hospital Infectious Disease and Signaling Research Center.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Tsai
authors.affiliation: Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts.
authors.forename: Shiaw-Lin
authors.initials: SL
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine Institute of Molecular Medicine, National Cheng Kung University Medical College Infectious Disease and Signaling Research Center.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005690:Galactose / Q000172:deficiency; D006031:Glycosylation; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020298:U937 Cells; D006023:Glycoproteins
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D005690:Galactose; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: IgG; chronic hepatitis B; glycosylation; liquid chromatography–mass spectrometry; liver histology