ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
transcription factor, NRF2 that regulates cytoprotective pathways is up-regulated in the livers of younger
donors and that increased expression of this transcription factor means a better outcome post-transplant.
Badar Zaman, Martin Leonard (Conway Institute, UCD), Elizabeth Ryan, Cormac Taylor (Conway
Institute, UCD), Justin Geoghegan, Cliona O’Farrelly.
Hepatic Malignancy
CD1d is a restriction element for natural killer (NK) T cells, a sub-population of lymphocytes expressing a T
cell receptor together with NK cell markers. CD1d molecules bind and present lipids to these NKT cells
resulting in activation and production of cytokines. Immune regulatory functions such as development of
tolerance, regulation of autoimmunity, and potent antitumour and antiviral activities have been ascribed to
NKT cells. The aim of this study is to investigate the role of CD1d isoforms in regulating immune responses
to malignancy.
Margaret O’Brien, Emma McGrath, Cliona O’Farrelly
HCV & It’s effect on Bone Metabolism
Does chronic HCV infection increase the risk for the development of Osteoporosis?
Osteopenia (thin bones) and osteoporosis (brittle bones) are common among patients with chronic liver
disease. The purpose of this study is to investigate the frequency of bone disease in a group of women
infected with hepatitis C virus (HCV) via contaminated anti-D. The underlying mechanisms by which chronic
HCV may cause osteoporosis are not fully understood, but individuals chronically infected with HCV have
ongoing inflammation. We want to determine if this inflammation causes an increase in bone breakdown.
Bone mineral density and markers of inflammation in individuals with persistent infection will be compared
to those who have cleared the infection.
Kavin Nanda, Elizabeth Ryan, Barbara Murray, Malachi McKenna, John Hegarty, Cliona O’Farrelly
IL-10 and TGF-‚ mediated suppression of antigen-specific Th1 and Th17 responses during HCV infection
We have shown that antigen-specific IL-10-secreting regulatory T (Treg) cells are induced in patients
chronically infected with HCV. We found that HCV nonstructural protein 4 (NS4) induces IL-10, and inhibits
IL-12 production by monocytes. We also found that PBMC from HCV infected patients secreted significant
concentrations of IL-10, but low concentrations of IFN-γ and IL-17 in response to NS4. Addition of a
neutrailizing antibody to IL-10 significantly enhanced NS4-specific IFN-γ, but not IL-17 production. In
contrast, IL-17 was enhanced by neutralisation of TGF-β. Our findings suggest that HCV subverts virusspecific
Th1 responses through the induction of IL-10 from monocytes and Treg cells and suppresses Th1
and Th17 cells through TGFβ‚ production. This may in part explain the failure to clear the chronic infection.
Aileen Rowan (TCD), Elizabeth Ryan, John Hegarty, Cliona O’Farrelly, Kingston Mills (TCD)
Cytokine and chemokine signatures predictive of the response of HCV patients to therapy
IFN-α in combination with Ribavirin is the current standard treatment for chronic HCV infection. However,
more than 50% of patients do not respond to this combination therapy and suffer significant side effects
unnecessarily. We propose to design an assay based on these characteristic signatures that will be used to
predict the potential efficacy of IFNα/Ribavirin therapy on an individual patient basis, prior to commencement
of treatment. Chemokines and cytokines that are over- or under-expressed in non-responders will be potential
Return to Contents
34