title: Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection.
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
  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.
authors.affiliation: Drexel University College of Medicine, and Department of Microbiology and Immunology and Drexel Institute for Biotechnology and Virology, Doylestown, Pennsylvania, USA. anne.lamontagne@drexelmed.edu
authors.forename: Anne
authors.initials: A
authors.lastname: Lamontagne
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Long
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Comunale
authors.forename: Julie
authors.initials: J
authors.lastname: Hafner
authors.forename: Lucy
authors.initials: L
authors.lastname: Rodemich-Betesh
authors.forename: Mengjun
authors.initials: M
authors.lastname: Wang
authors.forename: Jorge
authors.initials: J
authors.lastname: Marrero
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Timothy
authors.initials: T
authors.lastname: Block
authors.forename: Anand
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000907:Antibodies, Bacterial / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D011134:Polysaccharides; D003165:Complement System Proteins; D007372:Interferons