HLA alleles in combination with innate immune genes are key determinants of viral outcome in Hepatitis C virus infection

Abstract

s 345 HLA ALLELES IN COMBINATION WITH INNATE IMMUNE GENES ARE KEY DETERMINANTS OF VIRAL OUTCOME IN HEPATITIS C VIRUS INFECTION Karen Fitzmaurice, Jacob Hurst , Megan Dring , Clair Gardiner , Paul Klenerman , Irish HCv Research Consortium University of Oxford, Oxford, UK Trinity College Dublin, Dublin, Ireland Background: Chronic Hepatitis C virus (HCV) infection is a leading cause of liver related morbidity. Both the innate and adaptive immune response are thought to be important in determining viral outcomes. Polymorphisms associated with the IL28B gene are strongly associated with both spontaneous and treatment outcomes. This study investigates the importance of HLA genes in the context of polymorphisms in the innate immune genes IL28B and KIR. Methods: We assess the influence of HLA Class I and II genes on viral outcomes in an Irish cohort of women who had been infected from a single source. In this cohort, a number of HLA alleles are associated with different outcomes and the impact of IL28B polymorphisms as a determinant of outcome is profound. Genotyping on 319 women was available. Results: Logistic regression was performed and indicates that the HLA-A*03 (OR 0.36 [0.15-0.89], p1⁄40.027) -B*27 (OR 0.12[0.03-0.45], p1⁄4<0.001), -DRB1*0101 (OR 0.2 [0.070.61], p1⁄40.005), -DRB1*0401 (OR 0.31 [0.12-0.85, p1⁄40.02) and the CC IL28B rs12979860 genotype (OR 0.1 [0.040.23], p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*0201 (OR 4.2 (2.04-8.66], P1⁄40.008), KIR2DS3 (OR 4.36 [1.62-11.74], p1⁄40.004) and IL28B rs12979860 IL28B CT/TT genotype (OR 0.1[0.040.23], p<0.001) are associated with chronic infection. This study finds no interactive effect between IL28B and these Class I and II alleles in relation to viral clearance. There is however, a strong additive effect. Conclusions: This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response. http://dx.doi.org/10.1016/j.jinf.2013.07.008 AN ADENOVIRAL MODEL TO UNLOCK THE SECRETS OF MEMORY INFLATION? Julia Colston, Beatrice Bolinger , Alison Turner , Sarah Gilbert , Paul Klenerman 1 Oxford University e The Peter Medawar Building for Pathogen Research, Oxford, UK Oxford University e The Jenner Institute, Oxford, UK