Abnormal CD4+T helper (Th) 1 cells and activated memory B cells are associated with type III asymptomatic mixed cryoglobulinemia in HCV infection

Background: Mixed cryoglobulinemia (MC) in hepatitis C virus (HCV) infection is associated with abnormal immune responses mediated by T cells and B cells, while the relationships of different subsets of CD4 + T helper (Th) cells, B cells and associated cytokines with type III asymptomatic MC in HCV infection are poorly understood. Methods: Fifty-four chronic hepatitis C (CHC) patients and 23 healthy controls (HCs) were enrolled in the study. Serum cryoglobulins were detected by cryoprecipitation. The types of cryoglobulin were determined by western blot. The phenotypes and frequencies of Th cell and B cell subsets were detected by flow cytometric analysis. The cytokines IFN-gamma, IL-4, IL-17, IL-21, IL-22, and TGF-beta were measured by enzyme-linked immunosorbent assay. Results: Twenty-six CHC patients were detected with type III asymptomatic MC. The frequencies of Th2, Th17, follicular helper T (Tfh cells), Th22, and tissue-like B cells were significantly higher in CHC patients compared to HCs, while these cell subsets were not significantly different between CHC patients and HCV-related MC patients. The frequencies of Th1 and activated memory B cells increased in HCV-related MC patients compared to HCs, although the difference between the two cell subsets in CHC patients and HCs was not significant. The frequency of regulatory T cells (Treg cells) was higher in CHC patients than in HCV-related MC patients and HCs. Higher expressions of serum IFN-gamma, IL-17, IL-21, and IL-22 were observed in CHC patients than in HCs, but the differences were not significantly different in CHC patients and HCV-related MC patients. The frequency of Th1 cells was associated with activated memory B cells in HCV-related MC patients, and the frequency of Th1 cells and activated memory B cells was closely related to HCV RNA in HCV-related MC patients. Conclusions: The increased frequencies of Th17 cells, Tfh cells, Th22 cells, Treg cells, cytokines IL-17, IL-21, IL-22, and tissue-like B cells, were related to HCV infection but not type III asymptomatic MC. Higher frequencies of Th1 cells and activated memory B cells were associated with type III asymptomatic MC in HCV infection.