Aberrant Serum Immunoglobulin G Glycosylation in Chronic Hepatitis B Is Associated With Histological Liver Damage and Reversible by Antiviral Therapy

作者：Ho Cheng Hsun; Chien Rong Nan; Cheng Pin Nan; Liu Jia Huei; Liu Cheng Kun; Su Chih Sheng; Wu I Chin; Li I Chen; Tsai Hung Wen; Wu Shiaw Lin; Liu Wen Chun; Chen Shu Hui; Chang Ting Tsung^*

来源：Journal of Infectious Diseases, 2015, 211(1): 115-124.

DOI：10.1093/infdis/jiu388

• chronic hepatitis B
• IgG
• glycosylation
• liver histology
• liquid chromatography-mass spectrometry

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.

• 出版日期2015-1-1
• 单位长春大学; 东北大学