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J Infect Dis. 2015 Jan 1;211(1):115-24. doi: 10.1093/infdis/jiu388. Epub 2014 Jul 10.

Aberrant serum immunoglobulin G glycosylation in chronic hepatitis B is associated with histological liver damage and reversible by antiviral therapy.

Author information

1
Department of Internal Medicine.
2
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
3
Institute of Molecular Medicine, National Cheng Kung University Medical College.
4
Department of Pathology, National Cheng Kung University Hospital Infectious Disease and Signaling Research Center.
5
Barnett Institute and Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts.
6
Department of Chemistry, National Cheng Kung University, Tainan.
7
Department of Internal Medicine Institute of Molecular Medicine, National Cheng Kung University Medical College Infectious Disease and Signaling Research Center.

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.

KEYWORDS:

IgG; chronic hepatitis B; glycosylation; liquid chromatography–mass spectrometry; liver histology

PMID:
25015948
DOI:
10.1093/infdis/jiu388
[Indexed for MEDLINE]

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