Journal article
Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection
PloS one, v 8(6), pp e64992-e64992
2013
PMID: 23750224
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Using comparative glycoproteomics, we have previously identified a glycoprotein that is altered in both amount and glycosylation as a function of liver cirrhosis. The altered glycoprotein is an agalactosylated (G0) immunoglobulin G molecule (IgG) that recognizes the heterophilic alpha-gal epitope. Since the alpha gal epitope is found on gut enterobacteria, it has been hypothesized that anti-gal antibodies are generated as a result of increased bacterial exposure in patients with liver disease.
The N-linked glycosylation of anti-gal IgG molecules from patients with fibrosis and cirrhosis was determined and the effector function of anti-bacterial antibodies from over 100 patients examined. In addition, markers of microbial exposure were determined.
Surprisingly, the subset of agalactosylated anti-gal antibodies described here, was impaired in their ability to mediate complement mediated lysis and inhibited the complement-mediated destruction of common gut bacteria. In an analysis of serum from more than 100 patients with liver disease, we have shown that those with increased levels of this modified anti-gal antibody had increased levels of markers of bacterial exposure.
Anti-gal antibodies in patients with liver cirrhosis were reduced in their ability to mediate complement mediated lysis of target cells. As bacterial infection is a major complication in patients with cirrhosis and bacterial products such as LPS are thought to play a major role in the development and progression of liver fibrosis, this finding has many clinical implications in the etiology, prognosis and treatment of liver disease.
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Details
- Title
- Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection
- Creators
- Anne Lamontagne - Drexel University College of Medicine, and Department of Microbiology and Immunology and Drexel Institute for Biotechnology and Virology, Doylestown, Pennsylvania, USA. anne.lamontagne@drexelmed.eduRonald E LongMary Ann ComunaleJulie HafnerLucy Rodemich-BeteshMengjun WangJorge MarreroAdrian M Di BisceglieTimothy BlockAnand Mehta
- Publication Details
- PloS one, v 8(6), pp e64992-e64992
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- UO1 CA084951-06 / NCI NIH HHS R01 CA120206 / NCI NIH HHS U01 CA084951 / NCI NIH HHS R01 CA120206-01 / NCI NIH HHS U01 CA168856 / NCI NIH HHS R42 CA121506 / NCI NIH HHS R42 CA121506-02 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000319961900026
- Scopus ID
- 2-s2.0-84878643958
- Other Identifier
- 991014878158504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Multidisciplinary Sciences