No abstract

IntroductionDepletion of cellular pool and constant activation of plasmacytoid dendritic cells (pDCs) in HIV-infected persons (HIV+) are associated with disease progression and manifestation of opportunistic infections. The influence of highly-active antiretroviral treatment (HAART) and suppressed HCV-co-infection (HIV+/HCV+) on the extent of these changes remains unknown.ObjectiveTo study parameters of pDCs in peripheral blood of HIV+ and HIV+/HCV+ patients on HAART.MethodsTwelve uninfected with HIV or HCV volunteers and 37 patients (12 HIV+, 9 HIV+/HCV+ and 16 HCV+) were enrolled. All HIV+ patients received HAART and had undetermined HIV viral load. All HCV+ patients had finished antiviral therapy (Pegasys/ribavirin) with sustained viral response for six months and more. The pDC population was enumerated by flow cytometry. In vitro IFN production in the whole blood in response to pDC-specific stimulus unmethylated CpG oligonucleotides was determined by enzyme-linked immunosorbent assay (ELISA).ResultsThe percentage of pDCs of peripheral blood mononuclear cells (PBMC) in HIV+/HCV+ was the lowest (0.08±0.02) but statistically not different from HIV+ (0.15±0.03; p=0.11) and significantly lower than HCV+ (0.17±0.015; p=0.4) and controls (0.27±0.045; p=0.03). Absolute number of pDCs in HIV+ on HAART (6.3±1.3) was not significantly lower than the control (10.25±1.75; p=0.09) but in HIV+/HCV+ (5.1±1.2; p=0.03), the difference was valid. IFN-alpha production by pDCs in patients on HAART in HIV+ (2.4±0.9 pg/µl) and in HIV+/HCV+ (3.7±1 pg/µl) patients were significantly higher than in controls (in controls IFN-alpha production by pDCs in the native plasma was below the level of detection (3 pg/µl), p=0.02 and p=0.0014).ConclusionsAbsolute number of pDC in HIV-positive person on HAART with sustained viral response to treatment of HCV-co-infection was lower than in HIV-mono-infected. IFN-alpha production by pDC in HIV+ and in HIV+/HCV+ patients receiving HAART remains higher than in uninfected persons.

Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.

A new approach in understanding the mechanisms of immune response in viral hepatitis is the discovery of a unique type of immune cells – plasmocytoid dendritic cells (pDCs). Plasmocytoid dendritic cells (pDCs) are cells of lymphoid origin and morphologically resemble plasma cells. Functionally, they are professional IFN-a-producing cells that play an important role in antiviral immune response. Data on the mechanisms of PDCs participation in hepatitis B virus infection are few and contradictory. In chronic HBV infection, the role of pDCs remains mysterious and poorly understood with conflicting circulating blood pDCs results that show differently that they are not affected or reduced. However, functional disorders of pDCs were observed in patients with chronic HBV infection. The establishment of these mechanisms, as well as the search for the cause of hepatitis B virus latency and the formation of chronic infection remains one of the important and promising areas of scientific activities today.