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

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

Abstract

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.

Keywords

Portal Tract Mixed Cryoglobulinemia Cutaneous Vasculitis Cryoglobulinemic Vasculitis Mixed Cryoglobulinemia Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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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