title: Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection.
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.
authors.affiliation: Institute for Immunology, Klinikum Grosshadern, University of Munich, Munich, Germany. axel@ulsenheimer.de
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: J Tilman
authors.initials: JT
authors.lastname: Gerlach
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
authors.forename: Norbert
authors.initials: N
authors.lastname: Gruener
authors.forename: Martin
authors.initials: M
authors.lastname: Wächtler
authors.forename: Markus
authors.initials: M
authors.lastname: Backmund
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: Winfried
authors.initials: W
authors.lastname: Schraut
authors.forename: Malte H J
authors.initials: MH
authors.lastname: Heeg
authors.forename: Carl A
authors.initials: CA
authors.lastname: Schirren
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Pape
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006526:Hepatitis C / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis
chemical_list: C515370:CCR7 protein, human; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D054400:Receptors, CCR7; D019707:Receptors, Chemokine