AUTHOR=Sidharthan Sreetha , Kim Cheol-Woo , Murphy Alison A. , Zhang Xiaozhen , Yang Jun , Lempicki Richard A. , Sneller Michael C. , Kottilil Shyam 

TITLE=Hepatitis C-Associated Mixed Cryoglobulinemic Vasculitis Induces Differential Gene Expression in Peripheral Mononuclear Cells

JOURNAL=Frontiers in Immunology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00248

DOI=10.3389/fimmu.2014.00248

ISSN=1664-3224

ABSTRACT=<p>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 <italic>in vivo</italic> B cell depletion therapy is critical to completely understanding the mechanisms of MC vasculitis pathogenesis.</p>