title: Hepatitis C-associated mixed cryoglobulinemic vasculitis induces differential gene expression in peripheral mononuclear cells.
abstract: This study examines the distinct gene expression profile of peripheral blood mononuclear cells from patients with chronic hepatitis C infection and mixed cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised neutrophil function, impaired chemotaxis, and increased interferon-stimulated gene (ISG) expression, contributing to overall MC pathogenesis and end-organ damage. Increased ISG expression is suggestive of an enhanced endogenous interferon gene signature. PBMC depletion assays demonstrate that this increased expression is likely due to an activation of monocytes and not a direct result of B cell expansion. Notably, this monocyte activation of ISG expression in HCV-associated MC vasculitis suggests a poor predictor status of interferon-based treatment. Further analysis of PBMC gene expression profiles before and after in vivo B cell depletion therapy is critical to completely understanding the mechanisms of MC vasculitis pathogenesis.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Department of Health and Human Services , Bethesda, MD , USA.
authors.forename: Sreetha
authors.initials: S
authors.lastname: Sidharthan
authors.affiliation: Department of Internal Medicine, Inha University , Incheon , South Korea.
authors.forename: Cheol-Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services , Bethesda, MD , USA.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Murphy
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services , Bethesda, MD , USA.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services , Bethesda, MD , USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sneller
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services , Bethesda, MD , USA.
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
keywords: hepatitis C; interferon-stimulated genes; mixed cryoglobulinemia; vasculitis