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PERIPHERAL BLOOD DENDRITIC CELL SUBSETS AND SERUM INTERLEUKIN-12 LEVELS IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: RELATION TO DISEASE ACTIVITY
Hoda El Aggan1, Nahla Farahat2, Fathallah Mohamed1, Eman Emam3, Enas Gaballah1
Department of Medicine (Hepatobiliary Unit)1, Clinical Pathology2 and Pathology3, Faculty of Medicine, University of Alexandria, Egypt
Background/AIM: T-cell immune responses appear to influence the outcome of Hepatitis C virus (HCV) infection and require activation by antigen presenting cells like dendritic cells (DC). Therefore, the present work was designed to study the DC subsets (myeloid and lymphoid) in peripheral blood and to assess the serum levels of interleukin-12 (IL-12) in patients with chronic hepatitis C in relation to disease activity.
METHODS: 28 patients with chronic hepatitis C (15 with elevated serum levels of alanine aminotransferase (ALT) and 13 with persistently normal ALT levels) and 12 healthy subjects were included in the study. All patients had seropositivity for anti-HCV antibodies and HCV RNA. Dendritic cells in peripheral blood were identified using 3-color flow cytometric assay as lineage marker negative (lin-)/HLA-DR positive cells. The differentiation of myeloid DC subset from lymphoid DC subset was based on the expression of CD11c or CD123 on the cell surface respectively. Quantitative determination of IL-12p70 heterodimer in serum was performed using a solid phase sandwich enzyme-linked immunosorbent assay kit.
RESULTS: The percentages of peripheral blood DC subsets (CD11c+ and CD123+), the CD11c+ DC/CD123+ DC ratio and the serum IL-12 levels were significantly lower in chronic hepatitis C patients than in healthy subjects and in patients with elevated ALT than in those with normal ALT (P < 0.05). The reduction in circulating DC subsets and serum IL-12 levels showed negative correlations with serum levels of ALT and the histopathological grading and staging scores (P < 0.05) but not with serum HCV RNA levels (P > 0.05).
CONCLUSIONS: Patients with chronic HCV infection had significant deficiencies in circulating DC, particularly the myeloid subset and in IL-12 production, which were correlated with disease activity and hepatocellular injury. These findings suggest that DC and IL-12 may play a role in the progression of liver disease in chronic HCV infection and may provide a potential new goal for HCV immunotherapy.