The immunogenetics of Hepatitis C Virus in a defined unique cohort
Citation:
Susan McKiernan, 'The immunogenetics of Hepatitis C Virus in a defined unique cohort', [thesis], Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical Medicine, 2006, pp 142Download Item:
Abstract:
Hepatitis C virus is a major cause of liver-related morbidity and mortality worldwide as chronic infection develops in up to 80% of those infected and leads to end-stage liver disease in a significant percentage. The mechanisms of viral clearance and the pathogenesis of liver injury are poorly understood due to the lack of appropriate animal or cell culture models. Current opinion suggests that viral clearance is mediated by a strong and multi-specitlc response from both T helper cells and cytotoxic T lyinphocytes (CTL), with a Th-1 like cytokine profile and that liver injury is due to the host immune response to infected hepatocytes caused predominantly by activated CTL's. Activation of both these cell lines is dependent on viral peptide presentation by Major Histocompatibility Complex (MHC) class I and II alleles, which are inherited as a haplotype. Several studies have shown an association between various class II alleles and viral outcome whereas the association with class I alleles has been less well demonstrated. In Ireland, a cohort of Rhesus negative women received anti-D immunoglobulin in 1977 that was infected with HCV, genotype Ib originating from a single donor. Follow-up in 1994, demonstrated that a greater than expected number of women cleared HCV and that the disease progression was milder than to be expected. This suggests that in this unique cohort there exists a strong genetic influence on the outcome of HCV infection. Hence the aim of this study was to examine the Human Leujocyte Antigen class 1 and II alleles for any associations with outcome in HCV infection and to extend this search into the class III region of the MHC, specifically the Tumor Necrosis Factor (TNF) region.
Author: McKiernan, Susan
Advisor:
Kelleher, DermotQualification name:
Doctor of Medicine (M.D.)Publisher:
Trinity College (Dublin, Ireland). School of Medicine. Discipline of Clinical MedicineNote:
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