title: Involvement of chemokines and type 1 cytokines in the pathogenesis of hepatitis C virus-associated mixed cryoglobulinemia vasculitis neuropathy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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-gamma and 7.2 +/- 1.9 for tumor necrosis factor alpha), 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 1alpha [MIP-1alpha], 19.9 +/- 5.7 for MIP-1beta, and 7.2 +/- 1.5 for CXCR3). Compared with patients with idiopathic PAN, there was a trend toward higher expression of MIP-1alpha and CXCR3 in HCV-MC vasculitis patients (mean +/- SEM fold increase 27.4 +/- 8.3 versus 5.3 +/- 3.4 for MIP-1alpha and 7.2 +/- 1.5 versus 2.5 +/- 0.9 for CXCR3).
  
  
  CONCLUSIONS
  This study is the first to demonstrate a role of cellular immunity and Th1 lymphocytes in the pathogenesis of HCV-MC vasculitic nerve lesions.
authors.affiliation: Hôpital Pitié Salpêtrière, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.forename: Thierry
authors.initials: T
authors.lastname: Maisonobe
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D003449:Cryoglobulinemia / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010543:Peroneal Nerve / Q000378:metabolism / Q000473:pathology; D010488:Polyarteritis Nodosa / Q000378:metabolism; D011115:Polyneuropathies / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma