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Published on: February 3, 2012
Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection
Axel Ulsenheimer1, J Tilman Gerlach, Maria-Christina Jung
1Institute for Immunology, Klinikum Grosshadern, University of Munich, Munich, Germany. axel@ulsenheimer.de
Insights
Plasmacytoid dendritic cells (pDCs) are significantly reduced and less functional in acute hepatitis C (aHC), correlating with liver inflammation. This impaired pDC function may hinder the body's ability to produce interferon-alpha and clear the virus.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Acute hepatitis C (aHC) often progresses to chronic hepatitis C (cHC), but early treatment can prevent this.
- Plasmacytoid dendritic cells (pDCs) are key producers of endogenous interferon-alpha (IFN-alpha), crucial for viral clearance.
- The role of pDCs in the pathogenesis of aHC remains largely unknown.
Purpose of the Study:
- To investigate the frequency, phenotype, and function of pDCs in patients with aHC.
- To compare pDC characteristics in aHC with those in chronic hepatitis C (cHC), acute hepatitis B (aHB), nonviral inflammatory diseases, and healthy controls.
- To determine the correlation between pDC function and liver inflammation markers in aHC.
Main Methods:
- Analysis of pDC frequency and phenotype (HLA-DR, CCR7 expression) in peripheral blood.
- Measurement of IFN-alpha production by pDCs.
- Comparison of pDC parameters across different patient groups (aHC, cHC, aHB, nonviral inflammatory disease) and healthy controls.
- Correlation analysis between pDC frequency/function and alanine aminotransferase (ALT) levels.
Main Results:
- Patients with aHC exhibited significantly reduced peripheral blood pDC frequency compared to healthy controls.
- Circulating pDCs in aHC were immature, with reduced HLA-DR and CCR7 expression, and produced significantly less IFN-alpha.
- pDC frequency in aHC was inversely correlated with ALT levels, indicating greater liver inflammation.
- Less pronounced alterations in pDC frequency and function were observed in cHC, aHB, and nonviral inflammatory disease groups.
Conclusions:
- Peripheral blood pDCs are dramatically reduced in frequency and IFN-alpha-producing capacity during aHC.
- The impaired pDC function in aHC is inversely related to the severity of liver inflammation.
- In cHC, pDC function shows incomplete recovery, potentially influenced by the ongoing inflammatory state.
Abstract:
Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients but can frequently be prevented by early treatment with interferon (IFN)-alpha. Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN-alpha producers, but their role in aHC is unknown. In this study, frequency, phenotype, and pDC function were analyzed in 13 patients with aHC and 32 patients with chronic hepatitis C (cHC) compared with 20 healthy controls, 33 sustained responders to antiviral treatment, 14 patients with acute hepatitis B (aHB), and 21 patients with nonviral inflammatory disease. In aHC, pDCs in the peripheral blood were significantly reduced compared with healthy controls (median, 0.1% vs. 0.36%, P < .0005) and were inversely correlated to alanine aminotransferase levels (r = -0.823; P < .005). Circulating pDCs in aHC were immature, as determined via reduced expression of HLA-DR and CCR7, and produced little amounts of IFN-alpha (median, 3.5 pg/50,000 peripheral blood mononuclear cells [PBMCs] vs. 498.4 pg/50,000 PBMCs in healthy controls; P < .0005). Less pronounced changes were present in cHC (median, 0.17%, 28.0 pg/50,000 PBMCs IFN-alpha, respectively). However, a significantly reduced frequency and IFN-alpha production was also found in self-limited aHB (median 0.1%, 8.6 pg/50,000 PBMCs) and in patients with nonviral inflammatory disease (median 0.19%, 7.5 pg/50,000 PBMCs). In conclusion, in aHC frequency and IFN-alpha-producing capacity of peripheral blood pDCs are dramatically reduced and inversely correlated with the degree of liver inflammation. In cHC there is incomplete recovery of pDC function, which, however, could be solely due to the chronic inflammatory state.
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