NK cell phenotypic and functional shifts coincide with specific clinical phases in the natural history of chronic HBV infection

Background: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection. Methods: Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells. Results: The overall composition, phenotype, and cytolytic activity of the NM cells remained constant across all clinical phases, with the exception of a few specific markers (KIRs, NKp46). CD56(bright) NM cells of chronic HBV patients differed in their ability to produce IFN-gamma between the clinical phases pre-and post-HBeAg seroconversion. Conclusion: This depicts a shift in NM cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides with HBeAg seroconversion. Although these changes in NM cells do not appear to be completely responsible for differences in liver damage characteristic of specific clinical phases, they could provide a step toward understanding immune dysregulation in chronic HBV infection. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license