Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus-induced mixed cryoglobulinemia vasculitis

Arthritis Rheum. 2008 Sep;58(9):2897-907. doi: 10.1002/art.23759.


Objective: Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. We previously reported that MC vasculitis is associated with a quantitative defect of peripheral blood regulatory T cells. The aim of this study was to prospectively evaluate the evolution of this defect during the course of antiviral treatment.

Methods: Treg cell frequencies and numbers were analyzed in 131 patients with chronic HCV infection (including 66 with MC vasculitis) and 20 healthy volunteer donors. Measurements were taken before, during, and after treatment with PEGylated interferon alfa-2b plus ribavirin.

Results: At baseline, patients with MC vasculitis had a significantly lower frequency and number of Treg cells than did patients without MC vasculitis. Complete remission of MC vasculitis following antiviral treatment was associated with a significant increase in Treg cell levels compared with baseline. In contrast, Treg cell levels in nonresponders or partial responders, which did not differ from those in complete responders at baseline, remained unchanged over the course of the study.

Conclusion: The strong positive correlation between clinical responses and Treg cell levels provides further support for the central role of Treg cells in the pathogenesis of HCV-induced MC vasculitis and emphasizes the dual role of Treg cells in chronic HCV infection: while Treg cells may hinder viral elimination, they also limit autoimmune injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • Cell Count
  • Cryoglobulinemia / complications
  • Cryoglobulinemia / drug therapy*
  • Cryoglobulinemia / immunology
  • Cryoglobulinemia / virology
  • Drug Therapy, Combination
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Remission Induction
  • Ribavirin / therapeutic use*
  • Statistics, Nonparametric
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Treatment Outcome
  • Vasculitis / complications
  • Vasculitis / drug therapy*
  • Vasculitis / immunology
  • Vasculitis / virology


  • Antiviral Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Ribavirin