Abstract | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS:
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Authors | Anne Lamontagne, Ronald E Long, Mary Ann Comunale, Julie Hafner, Lucy Rodemich-Betesh, Mengjun Wang, Jorge Marrero, Adrian M Di Bisceglie, Timothy Block, Anand Mehta |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 6
Pg. e64992
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23750224
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Bacterial
- Polysaccharides
- Complement System Proteins
- Interferons
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Topics |
- Antibodies, Bacterial
(metabolism)
- Complement System Proteins
(metabolism)
- Female
- Glycosylation
- Hepatitis C, Chronic
(complications, drug therapy, metabolism, microbiology)
- Humans
- Interferons
(therapeutic use)
- Liver Cirrhosis
(complications)
- Male
- Middle Aged
- Polysaccharides
(metabolism)
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