Involvement of chemokines and type 1 cytokines in the pathogenesis of hepatitis C virus–associated mixed cryoglobulinemia vasculitis neuropathy




To examine the expression profiles of a large number of genes within typical vasculitic nerve lesions in patients with mixed cryoglobulinemia (MC) vasculitis in order to better characterize the molecules involved in cellular tissue activation and trafficking.


The quantitative expression of 19 genes coding for cytokines, chemokines, and their receptors in the nerve lesions of 9 patients with hepatitis C virus (HCV)–associated MC vasculitis, 7 with idiopathic polyarteritis nodosa (PAN) (rheumatic disease controls), and 8 patients with noninflammatory idiopathic neuropathy (noninflammatory neuropathy controls) was assessed using a real-time reverse transcriptase–polymerase chain reaction procedure.


Compared with the noninflammatory controls, HCV-MC vasculitis patients had a significantly higher expression of Th1 cytokines in vasculitic nerve lesions (mean ± SEM fold increase 33.7 ± 11.6 for interferon-γ and 7.2 ± 1.9 for tumor necrosis factor α), whereas Th2 cytokines were absent (interleukin-4 [IL-4], IL-5, and IL-13) or were not significantly different (IL-10). Chemokines involved in T cell and monocyte trafficking were also significantly up-regulated in the HCV-MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 for macrophage inflammatory protein 1α [MIP-1α], 19.9 ± 5.7 for MIP-1β, and 7.2 ± 1.5 for CXCR3). Compared with patients with idiopathic PAN, there was a trend toward higher expression of MIP-1α and CXCR3 in HCV-MC vasculitis patients (mean ± SEM fold increase 27.4 ± 8.3 versus 5.3 ± 3.4 for MIP-1α and 7.2 ± 1.5 versus 2.5 ± 0.9 for CXCR3).


This study is the first to demonstrate a role of cellular immunity and Th1 lymphocytes in the pathogenesis of HCV-MC vasculitic nerve lesions.