Presentation: Regulatory T-Cells in Hepatitis C Virus-Induced Mixed Cryoglobulinemia Vasculitis (2007)

2015 Regulatory T-Cells in Hepatitis C Virus-Induced Mixed Cryoglobulinemia Vasculitis

Purpose:
Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. A previous report has demonstrated that this disorder is associated with lower levels of CD4+CD25 high regulatory T (Treg) cells. The aim of the study is to evaluate the effects of anti-viral treatment on Treg cells frequency and concentration in HCV infected patients with MC-vasculitis.
Methods: Measurement of CD4+CD25high and Forkhead box P3 (FOXP3) expression was performed in a group of 131 HCV chronically infected patients (66 with MC vasculitis, 22 with asymptomatic MC and 43 without MC), as well as in 15 healthy volunteers. Measurements were taken at baseline as well as during and after treatment with Pegylated Interferon and Ribavirin in 81 treated patients.
Results: At baseline, MC vasculitis is associated with lower levels of Treg cells compared with HCV positive patients without vasculitis (CD25high frequency in CD4+ population, 4.2%±0.2% and 4.9%±0.2%, respectively, p<0.05). Complete remission of MC vasculitis following anti-viral treatment was associated with an increase in Treg frequency (5.6±0.4%) compared with baseline levels (p<0.01) as well as compared with after treatment levels in patients with partial or no clinical response (4.1±0.4%, p<0.05). Although less pronounced, similar findings were found in association with sustained viral response (SVR) in MC vasculitis. These results were also confirmed with FOXP3+ staining.
At baseline, HCV infection without MC-vasculitis was associated with a higher level of Treg cells, compared with healthy controls and MC vasculitis patients. Following anti-viral treatment, an increase in Treg frequency was observed in patients without a SVR (6.1±8%) compared to baseline levels (p<0.05), while Treg frequency remained unchanged in patients with SVR (4.9±5%), an opposite trend to that found in MC-vasculitis patients.
Conclusions: Treatment-naïve patients with HCV induced MC-vasculitis have lower Treg levels compared with patients without MC-vasculitis. Following antiviral treatment, complete remission in auto-immune manifestations as well as viral clearance, are associated with a significant increase in the Treg cell subset. These results offer additional support for a beneficial role for Treg cells in HCV infection, in curbing autoimmunity.

  D.A. Landau, Research supported by an ANRS (Nationl association for AIDS Research) grant, 2; M. Rosenzwajg, None; D. Saadoun, None; D. Klatzmann, None; P. Cacoub, None.