Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: an Egyptian study

Abstract

Aim: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia.

Methods: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis.

Results: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups.

Conclusion: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients.

Keywords: CD83; CD86, CD40; Dendritic cells; Hemodialysis; Hepatitis C virus; Hyaluronic acid; Interleukin-10; PD-L1; Uremia.

Figure 1

Relative quantitative gene expression of CD83, CD86, CD40 and PD-L1 in all study subjects expressed as mean ± SD. ^aP < 0.05 in both hepatitis C virus (HCV) patient groups vs control group; ^cP < 0.05 in the HCV patient group vs HCV uremic patients on hemodialysis.

Figure 2

Correlations. A: Between hepatitis C viremia and CD83. r = -0.98, P < 0.001, CD86: r = -0.866, P < 0.001, CD40: r = -0.98, P < 0.001, PD-L1: r = 0.889, P < 0.001; B: Between hepatitis C viremia in uremic patients on hemodialysis and CD83. r = -0.096, P > 0.05 NS, CD86: r = -0.588, P < 0.05, CD40: r = -0.946, P < 0.001, PD-L1: r = 0.663, P < 0.05. HCV: Hepatitis C virus; DC: Dendritic cell

Figure 3

Serum levels of hyaluronic acid (ng/mL) and interleukin-10 (pg/mL) in all study subjects expressed as mean ± SD. ^aP < 0.05 vs control group, ^cP < 0.05 in the hepatitis C virus (HCV) patient group vs HCV uremic patients on hemodialysis. IL-10: Interleukin-10.

Figure 4

Correlation analysis. A: Between hyaluronic acid levels and hepatitis activity score (P < 0.001); B: Between hyaluronic acid levels and fibrosis score (P < 0.001); C: Between interleukin-10 (IL-10) levels and fibrosis score (P < 0.001).