694 HLA CLASS I ALLELES ASSOCIATED WITH HCV POLYMORPHISMS AND RESPONSE TO ANTIVIRAL THERAPY IN HCV GENOTYPE 1-INFECTED PATIENTS

Introduction: Dys-regulated function of natural killer (NK) cells has been proposed as a mechanism contributing to viral persistence in hepatitis C virus (HCV) infection and HCV-associated liver damage. Recent data indicate that members of the signaling lymphocytic activating molecule (SLAM) family receptors (i.e. NTB-A, CRACC, and 2B4) and their respective ligands NTB-A, CRACC, and CD48 have important functions in NK cell biology. However, in hepatitis C expression of these molecules has not been studied in great detail. Methods: NK cells from 54 patients with chronic hepatitis C, 26 subjects who had achieved a sustained virological response after after antiviral therapy (n =26), and 47 healthy individuals were analysed by flow cytometry. Results: Expression of 2B4 and NTBA was not altered in HCV infection. However, expression of CRACC was significantly downregulated on CD56 NK cells in chronic hepatitis C (mean fluorescence index; HCV vs. healthy controls: 7.3 vs. 8.8, p < 0.01). In contrast to CRACC, expression of the ligand CD48 was significantly higher in the NK cell subsets from HCV-positive patients than in healthy controls (CD56: 32.92 vs. 26.37, p = 0.02; CD56: 12.79 vs. 9.6, p < 0.01). Interestingly, expression of CD48 on CD56 NK cells correlated positively with elevated aminotransferase levels (ALT: p = 0.02; AST: p < 0.01). Successful anti-viral treatment was associated with normalization of CD48 levels. Conclusions: This study demonstrates altered expression of the SLAM receptor CRACC and CD48 on NK cells in chronic hepatitis C. This phenotype may contribute to dys-regulated function of NK cells in HCV infections.