CD19 + CD24 hi CD38 hi regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C.

Objectives: Hepatitis C virus (HCV) infection is associated with abnormal immune responses. Since regulatory T (Tregs) and B (Bregs) cells modulate the progression of infectious diseases, this study aimed at examining how these cells are involved with the development of HCV infection. Methods: The frequencies of circulating Bregs and Tregs were characterized using flow cytometry. Both the association and dynamic changes of these cells with related clinical parameters were analyzed after Direct-Acting Antiviral (DAA) agent treatments. Additionally, both regulatory B and T and naive B and T cells were sorted and stimulated with healthy or HCV sera in vitro. Results: Bregs frequency in HCV-infected patients increased significantly and were positively correlated with levels of sera HCV RNA load, Alanine aminotransferase (AST) and total bilirubin (TBILI). Additionally, the increased Bregs returned to normal levels after DAA treatment. However, Tregs increased markedly in patients with HCV-cirrhosis and were significantly associated with Aspartate aminotransferase to Platelet Ratio Index (APRI) and Fibrosis 4 (FIB-4) scores. Furthermore, HCV sera doesn't expand either Tregs or Bregs, however, it does induce the IL-10 expression in B cells although it fails to induce FOXP3 expression in CD4(+) T cells. Conclusions: Increased Bregs not only may be associated with poor viral eradication and liver injury but also may provide a predictive marker of HCV disease therapeutic efficacy following DAA-treatment. HCV sera may selectively induce Bregs. Tregs probably do not control disease status in the early stages but may contribute to the progression of liver fibrosis in the late stages of HCV infection.