Add like
Add dislike
Add to saved papers

Fully galactosyl-fucosyl-bisected IgG 1 reduces anti-HBV efficacy and liver histological improvement.

N-glycosylation on the crystallizable fragment (Fc) governs antibody-mediated immune responses. This study addressed the relevance of N-acetylglucosamine (GlcNAc)-bisected IgG1 on the disease progression and treatment efficacy in the immune active phase of chronic hepatitis B virus (HBV) infection. Serum IgG1 N-glycan patterns from 166 HBV e antigen (HBeAg)-positive patients were analyzed using liquid chromatography-tandem mass spectrometry. The proportion of GlcNAc-bisected IgG1 on the disease severity and efficacy of nucleos(t)ide analogue treatment were investigated. Cytokine-dependent regulations of IgG1 GlcNAc bisection were also addressed using mouse IgG1 -producing hybridoma cells. We found that IgG1 bearing a fully galactosyl-fucosyl-N-acetylglucosamine-bisected (G2FN) glycoform in HBeAg-positive patients was associated with high levels of HBV DNA or HBV surface antigen, alanine aminotransferase <2 upper limits of normal, and a mild liver injury. Moreover, baseline IgG1 -G2FN ≧ 1.5% was linked to lower probabilities of virological response (HBV DNA undetectable in serum), HBeAg seroconversion, HBV core antigen loss, and liver histological improvement after treatment. Cox and logistic regression analyses revealed that IgG1 -G2FN was an unfavorable factor for the virological response (hazard ratio = 0.620, 95% confidence interval = 0.466-0.825, P = 0.001) or liver histological improvement (odds ratio = 0.513, 95% confidence interval = 0.279-0.943, P = 0.032), respectively. Results from in vitro studies showed that transforming growth factor (TGF)-β1 treatment downregulated mannosyl β-1,4-N-acetylglucosaminyltransferase 3 and β-1,4-galactosyltransferase 1 activities and thereby IgG1 -G2FN production, and this phenomenon reflected an inverse correlation between IgG1 -G2FN and TGF-β1 in sera of patients (r = -0.431, P < 0.001). In conclusion, IgG1 -G2FN was related to an attenuated liver inflammation and unfavorable treatment responses in patients with HBeAg-positive chronic hepatitis B.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app