Role of B-Cell-Attracting Chemokine-1 in HCV-Related Cryoglobulinemic Vasculitis

  • Sabino Russi
  • Silvia Sansonno
  • Gianfranco Lauletta
  • Domenico E. Sansonno
  • Franco Dammacco


B-cell-attracting chemokine-1 (BCA-1, CXCL13), also referred to as B-lymphocyte chemoattractant, is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection is frequently associated with B-cell dysfunction and lymphoproliferative disorders. Mixed cryoglobulinemia (MC) is a chronic immune complex-mediated disease strictly related to HCV infection and is mainly characterized by oligoclonal/monoclonal B-cell expansions potentially capable of progressing to B-cell non-Hodgkin’s lymphoma. In chronically HCV-infected patients with MC, circulating levels of BCA-1 were found to be higher than in healthy individuals. Interestingly, the highest BCA-1 levels strongly correlated with the active phase of cryoglobulinemic vasculitis. No direct relation was shown between BCA-1 levels and HCV circulating load, severity of liver disease, autoantibody production, cryoprotein levels, or complement consumption. Changes observed after B-cell depletion therapy suggest that B cells have little or no influence on BCA-1 transcription. Immunofluorescence demonstrated specific deposits of BCA-1 protein in the skin samples of patients with active cryoglobulinemic vasculitis, but not in those of MC patients with non-active vasculitis nor in those without MC. BCA-1 mRNA expression was confirmed in the skin of patients with deposits of BCA-1 immunoreactants. The elevated levels of circulating BCA-1 protein could be a cause of the impaired or altered trafficking of B cells in chronic HCV infection. BCA-1 is expressed at the site of cutaneous damage, where it may play a major role in the pathogenesis of skin manifestations in MC through a mechanism involving the chemoattraction of self-antigen-driven autoimmune B cells.


Portal Tract Mixed Cryoglobulinemia Cutaneous Vasculitis Cryoglobulinemic Vasculitis Mixed Cryoglobulinemia Patient 
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This study was supported in part by grants from: the Italian Medical Agency (AIFA), Research and Develop­ment Working Group (contract FARM7SJX), the Italian Association for Cancer Research (AIRC), and the University of Bari.


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Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Sabino Russi
    • 1
  • Silvia Sansonno
    • 2
  • Gianfranco Lauletta
    • 1
  • Domenico E. Sansonno
    • 3
  • Franco Dammacco
    • 4
  1. 1.Department of Internal Medicine and Human OncologyUniversity of Bari Medical SchoolBariItaly
  2. 2.Clinical and Experimental Pharmacology – DOMERTCentro di Riferimento OncologicoAvianoItaly
  3. 3.Liver Unit, Department of Biomedical Sciences and Clinical OncologyUniversity of Bari Medical SchoolBariItaly
  4. 4.Department of Biomedical Sciences and Clinical OncologyUniversity of Bari Medical SchoolBariItaly

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