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

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,group2 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 realtime 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 costimulatory markers;CD83,CD86 and CD40 in groups2 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-10was 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 and3,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 coinhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients.

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity

AIMTo investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODSA prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTSChronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSIONElevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.