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Hbc Alone Profile: Susceptibility versus Protection against Hepatitis B Virus could be associated with TNF Production

Araujo Patricia, Gonçalves Giovanna, Latinni Flavia, Barreto Jose Augusto and S Diaz Ricardo

Background: Donors with occult HBV (Hepatitis B virus) infection, defined as those who lacked detectable HBsAg but whose exposure to HBV infection was indicated by a positive anti-HBc (HBc alone) profile and the presence of HBV DNA, are a potential source of HBV infection. The aim of this study was to evaluate HBcAg-specific T cell responses, NK cell activity and cytokine levels in blood donors with HBc alone profiles with and without detectable viral DNA. Methods: From January 2010 to December 2012, a total of 4,252 HBc alone donations were obtained. Of the 4,252 donors, 681 donors had spontaneous HBV clearance (Co/s >10,0 by chemiluminescent assay, undetectable HBV DNA and reactivity to anti-HBc in subsequent donations), 3,097 were classified as false-positive for anti-HBc (Co/ s<6,0 in chemiluminescent assay, undetectable HBV DNA and no reactivity to anti-HBc in subsequent donations), 438 were classified as having chronic HBV infection (Co/s>10,0 in chemiluminescent assay, detectable HBV DNA and reactivity to anti-HBc in subsequent donations) and 36 were OBI (anti-HBc positive and detectable HBV DNA). There were 500 healthy blood donors and 434 HBV carriers (HBsAg, anti-HBc positive and detectable HBV DNA). NK cells were tested for cytotoxicity against K562 cells, serum levels of specific cytokines (IL-8, IL-1, IL-10, IL-12, IL-6 and TNF) were assayed by flow cytometry and HBcAg-specific T cell responses were assessed by lymphoproliferation reported in stimulation index (SI) units. Results: The IL-8 and IL-12 serum levels increased significantly (p<0.001) in HBV carriers and OBI, whereas the TNF-α serum levels increased significantly (p<0.001) in spontaneous HBV resolvers compared to HBV carriers and OBI. The serum levels of IL-1 and IL-10 were similar in HBV carrier, OBI and spontaneous HBV resolvers. Higher NK cytotoxic activity was observed in spontaneous HBV resolvers compared to HBV carriers, healthy donors and OBI. TNF-α correlated with NK cell activity in spontaneous HBV resolvers. A low intensity of HBcAg-specific T cell responses was observed in healthy donors (SI<3.0) and OBI (SI=8.0 to 10.0) compared to spontaneous HBV resolvers (SI>22.0). TNF-α was correlated with HBcAg-specific T cell responses in spontaneous HBV resolvers. Conclusion: Our results suggest that TNF-α production may be associated with protection against hepatitis B virus through increased NK cell activity and HBcAg-specific T cell responses in HBc alone blood donors.