Decreased numbers and impaired function of dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure

Abstract

Objective To investigate the frequencies of circulating dendritic cell (DC) subsets and the function of monocyte-derived dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure. Methods Peripheral blood was collected from hepatitis B-related acute-on-chronic liver failure patients (ACLF, n=40) and chronic hepatitis B (CHB, n=40) as well as normal controls (NCs, n=20). Circulating myeloid dendritic cell (Mdc) and plasmic dendritic cell (pDC) frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Purified monocytes were isolated by combination of Histopaque-1.077 and CD14 Microbeads. Monocyte-derived dendritic cells (MoDCs) generated in vitro in the presence of interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor upon activation by poly I∶C. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of MoDCs were detected in patients with hepatitis B-related ACLF. Results The number of circulating mDC decreased only in patients with hepatitis B-related ACLF compared with that in normal controls. However, pDC numbers decreased in both CHB and ACLF patients. We observed a further decrease the pDC numbers in ACLF compared to CHB patients without statistical significance (P>0.05). MoDC from ACLF patients showed lower expression of costimulatory molecules CD80, CD86 and the mature marker CD83, as well as MHC Ⅱ molecule (HLA-DR) compared to CHB and NC group. Interestingly, MoDC impaired allostimulatory mixed lymphocyte reaction from ACLF patients compared to those in CHB patients and NCs. Conclusions Patients with hepatitis B-related ACLF have a significantly lower expression of surface markers and impaired AMLR of MoDC, as well as decreased number of circulating mDC and pDC, which may be partially related to HBV disease progression in these patients. Key words: Liver failure, acute/ME; Dendritic cells/ME