Recovery Of Circulating Cd56^dim NK Cells And The Balance Of Th17/treg After Nucleoside Analogues Therapy In Chronic Hepatitis B Patients At Low Level Of HBsAG

ObjectiveThere is a lot of evidence that the soluble antigens secreted by hepatitis B virus?HBV?inhibit the function of the immune systems.The aim of this study is to explore after the treatment of nucleoside?acid?analogues?NAs?and virus replication was inhibited,whether the immune system of the patients who had achieved the peripheral blood HBV-DNA<1000IU/ml,hepatitis B e antigens?HBeAg?disappeared and hepatitis B surface antigens?HBsAg?decreased was reconstructed.MethodsThe frequency and phenotype of circulating natural killer?NK?cells,dendritic cells?DCs?,T-helper cells?Th?,regulatory T cells?Treg?,CD4⁺,CD8⁺T cells,T follicular helper?Tfh?and B cells subtypes were tested by flow cytometry in chronic hepatitis B?CHB?patients and healthy controls?HC?.HBV-related serum HBsAg,HBeAg,HBV-DNA loads,ALT and AST were determined.ResultsIn innate immune system,increased frequency of CD56^dimim NK cells were found in therapeutic response group?TR?compared to immune-active phase group?IA?.And in adaptive immune system,Th17/CD4⁺CD25⁺CD127^dimTreg ratio reduced in TR group.Besides,the frequency of CD40L⁺CXCR5⁺CD4⁺T cells and CD40⁺CD19⁺CD27⁺CD38⁺B cells was significantly higher than HCs,while the PDL1⁺CD19⁺B cells was lower.Furthermore,the frequency of CTLA4⁺CD4⁺T cells and CTLA4⁺CD8⁺T cells in CHB patients were significantly higher than HCs.ConclusionAfter NAs treatment and virus replication is inhibited,circulating CD56^dimim NK cells and the balance of Th17/Treg can be recovered.Restoring circulating CD56^dimim NK cells and the Th17/Treg balance may help patients reduce HBsAg.