The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included 2 testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. H epatitis C virus (HCV) is a hepatotropic virus with a high rate of chronic infection. It is known that progression to cirrhosis and hepatocellular carcinoma may take up to 20 years in individuals who are chronically infected and thus represents a leading cause of hepatocellular morbidity and mortality. [1][2][3][4] To date, viral factors (e.g., genotype) and host factors (e.g., age of acquisition, male sex, and alcohol consumption) are known to alter both the natural history of the disease and treatment outcomes. 2,4-6 As yet, no in vivo models of infection are available in HCV infection, therefore the pathogenic mechanism of disease remains unclear. 19.8%; P ‫؍‬ .002). In combination with previously reported class II allele associations, overIn HCV infection, recognition and elimination of infected cells by cytotoxic T lymphocytes (CTLs) require the presentation of specific HCV antigens on the membrane of hepatocytes in the context of HLA-A, -B and -C antigens. In acute HCV infection, animal models suggest that viral clearance appears to be dependent on an intrahepatic CTL response directed against multiple HCV antigens restricted by several class I molecules. 7 Human studies on peripheral blood similarly report that viral clearance is associated with a strong initial HCV-specific

Hepatitis C is a common infection with significant morbidity and mortality, and only a minority of patients successfully clear the infection. Identification of factors that influence disease progression in HCV infection is difficult owing to the lack of well-defined patient cohorts. However, recent evidence supports a role for the innate immune system in virus clearance. In this study, we investigated innate immune genes for their contribution to disease progression in a unique cohort of well-controlled HCV-infected patients. The Irish cohort of HCV patients is uniquely homogenous; patients were infected with a single genotype of HCV from contaminated anti-D Ig. We genotyped 543 infected patients, including 247 patients who spontaneously resolved infection, for natural killer (NK) cellassociated killer cell Ig-like receptors (KIR) genes and the recently reported IL28B (IFNλ3) SNP. The NK cell gene KIR2DS3 was significantly increased in patients with chronic infection [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.25-2.90, P < 0.002]. The IL28B "T" allele was also significantly increased in chronically infected patients (OR 7.38, 95% CI 4.93-11.07, P < 10). The presence of both markers synergized to significantly increase the risk of chronic infection over either factor alone (OR 20.11, 95% CI 9.05-44.68, P < 10 −7). In functional experiments, we found that IL28A significantly inhibited IFN-γ production by NK cells. Thus, we demonstrate a functional link between NK cells and type 3 IFN. Our findings may contribute to the development of a prognostic test for HCV and identify therapeutic strategies for the clinical management of HCV-infected patients.

No abstract

BackgroundThe relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that northesouth differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study.

Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents.