The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is ex...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Rambam Health Care Campus
2010-07-01
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| Series: | Rambam Maimonides Medical Journal |
| Subjects: | |
| Online Access: | http://rmmj.org.il/(S(zxxjbfamyql1hiaqpcgqoz00))/Pages/ArticleHTM.aspx?manuId=5 |
| _version_ | 1811273922003337216 |
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| author | Nazia Selzner Ahmed Helmy Katharina Foerster Oyedele A. Adeyi David R. Grant Gary Levy |
| author_facet | Nazia Selzner Ahmed Helmy Katharina Foerster Oyedele A. Adeyi David R. Grant Gary Levy |
| author_sort | Nazia Selzner |
| collection | DOAJ |
| description | Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection. |
| first_indexed | 2024-04-12T23:08:11Z |
| format | Article |
| id | doaj.art-a427df01de134dc09bce82bd4f642482 |
| institution | Directory Open Access Journal |
| issn | 2076-9172 |
| language | English |
| last_indexed | 2024-04-12T23:08:11Z |
| publishDate | 2010-07-01 |
| publisher | Rambam Health Care Campus |
| record_format | Article |
| series | Rambam Maimonides Medical Journal |
| spelling | doaj.art-a427df01de134dc09bce82bd4f6424822022-12-22T03:12:52ZengRambam Health Care CampusRambam Maimonides Medical Journal2076-91722010-07-0111e000410.5041/RMMJ.10004The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus InfectionNazia Selzner0Ahmed Helmy1Katharina Foerster2Oyedele A. Adeyi3David R. Grant4Gary Levy5Multi Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaMulti Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaMulti Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaMulti Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaMulti Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaMulti Organ Transplant Program, University Health Network, University of Toronto, Toronto, CanadaChronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection.http://rmmj.org.il/(S(zxxjbfamyql1hiaqpcgqoz00))/Pages/ArticleHTM.aspx?manuId=5FGL2TregimmunityregulationHCVMHV-3 |
| spellingShingle | Nazia Selzner Ahmed Helmy Katharina Foerster Oyedele A. Adeyi David R. Grant Gary Levy The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection Rambam Maimonides Medical Journal FGL2 Treg immunity regulation HCV MHV-3 |
| title | The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection |
| title_full | The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection |
| title_fullStr | The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection |
| title_full_unstemmed | The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection |
| title_short | The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection |
| title_sort | role of fgl2 in the pathogenesis and treatment of hepatitis c virus infection |
| topic | FGL2 Treg immunity regulation HCV MHV-3 |
| url | http://rmmj.org.il/(S(zxxjbfamyql1hiaqpcgqoz00))/Pages/ArticleHTM.aspx?manuId=5 |
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