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Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection.

Lamontagne A, Long RE, Comunale MA, Hafner J, Rodemich-Betesh L, Wang M, Marrero J, Di Bisceglie AM, Block T, Mehta A - PLoS ONE (2013)

Bottom Line: 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.In addition, markers of microbial exposure were determined.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.

View Article: PubMed Central - PubMed

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

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.

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Related in: MedlinePlus

Markers of bacterial exposure change in response to IFN therapy in patients with liver fibrosis.Patient sera were tested for sCD14 and LBP levels pre- and post- IFN therapy. In patients who respond to treatment, there is a statistically significant decrease in sCD14 following treatment (P<0.0001) while patients who do not respond show a significant increase following the course of treatment (P<0.0001) (B). There was no significant change LBP between treatment groups in patients who respond to IFN therapy (C), however patients who do not respond to treatment show a statistically significant increase from pre-treatment LBP levels (P<0.001) (D).
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pone-0064992-g006: Markers of bacterial exposure change in response to IFN therapy in patients with liver fibrosis.Patient sera were tested for sCD14 and LBP levels pre- and post- IFN therapy. In patients who respond to treatment, there is a statistically significant decrease in sCD14 following treatment (P<0.0001) while patients who do not respond show a significant increase following the course of treatment (P<0.0001) (B). There was no significant change LBP between treatment groups in patients who respond to IFN therapy (C), however patients who do not respond to treatment show a statistically significant increase from pre-treatment LBP levels (P<0.001) (D).

Mentions: In Figure 6, we examined the levels of peripheral markers of bacterial exposure in these patients and demonstrate that patients in the Responder group showed a significant decrease in sCD14 from 6088 ng/ml to 3905 ng/ml in response to IFN-therapy (P<0.0001) (Figure 6A). Conversely, in Non-responders the mean sCD14 increased from 6735 to 15244 ng/ml following treatment (Figure 6B).


Altered functionality of anti-bacterial antibodies in patients with chronic hepatitis C virus infection.

Lamontagne A, Long RE, Comunale MA, Hafner J, Rodemich-Betesh L, Wang M, Marrero J, Di Bisceglie AM, Block T, Mehta A - PLoS ONE (2013)

Markers of bacterial exposure change in response to IFN therapy in patients with liver fibrosis.Patient sera were tested for sCD14 and LBP levels pre- and post- IFN therapy. In patients who respond to treatment, there is a statistically significant decrease in sCD14 following treatment (P<0.0001) while patients who do not respond show a significant increase following the course of treatment (P<0.0001) (B). There was no significant change LBP between treatment groups in patients who respond to IFN therapy (C), however patients who do not respond to treatment show a statistically significant increase from pre-treatment LBP levels (P<0.001) (D).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672197&req=5

pone-0064992-g006: Markers of bacterial exposure change in response to IFN therapy in patients with liver fibrosis.Patient sera were tested for sCD14 and LBP levels pre- and post- IFN therapy. In patients who respond to treatment, there is a statistically significant decrease in sCD14 following treatment (P<0.0001) while patients who do not respond show a significant increase following the course of treatment (P<0.0001) (B). There was no significant change LBP between treatment groups in patients who respond to IFN therapy (C), however patients who do not respond to treatment show a statistically significant increase from pre-treatment LBP levels (P<0.001) (D).
Mentions: In Figure 6, we examined the levels of peripheral markers of bacterial exposure in these patients and demonstrate that patients in the Responder group showed a significant decrease in sCD14 from 6088 ng/ml to 3905 ng/ml in response to IFN-therapy (P<0.0001) (Figure 6A). Conversely, in Non-responders the mean sCD14 increased from 6735 to 15244 ng/ml following treatment (Figure 6B).

Bottom Line: 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.In addition, markers of microbial exposure were determined.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.

View Article: PubMed Central - PubMed

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

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.

Show MeSH
Related in: MedlinePlus