Clinical

Rituximab therapy for systemic vasculitis restores immune cell homeostasis

Last Updated: 2008-07-16 15:26:04 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment with rituximab leads to restoration of peripheral B- and T-lymphocyte homeostasis in patients with mixed cryoglobulinemia vasculitis, according to French researchers.

In the June 1st issue of Blood, Dr. Patrice Cacoub of Universite Pierre et Marie Curie, Paris and colleagues note that chronic infection with hepatitis C virus (HCV) is the main cause of this potentially life-threatening systemic vasculitis.

Although rituximab has been used to successfully treat the disorder, they add, little is known about the processes involved.

To investigate, the team studied 21 patients with HCV-related mixed cryoglobulinemia, of whom 14 achieved a complete response to rituximab. Also included were 50 healthy controls and 20 HCV patients without serum cryoglobulin and vasculitis.

Before treatment, the vasculitis patients showed significantly reduced naive B cells and CD4+CD25+FoxP3 regulatory T cells. Memory B cells were increased as were plasmablasts.

At 12 months or more after rituximab treatment and subsequent immune reconstitution, these abnormalities were reversed.

Patients who had a complete response showed a significant expansion of regulatory T cells and a significant decrease in CD8 T-cell activation. Both IL-12 and interferon-gamma production were significantly decreased.

The results, the researchers conclude, show that "B-cell depletion with rituximab dramatically improves abnormalities in B-cell homeostasis." Furthermore, "B-cell depletion may be an efficient therapy not only because it reduces or abolishes the hyperproduction of cryoglobulin, but also because this treatment improves T-cell homeostasis in restoring the regulation/activation and Th1/Th2 imbalances."

Blood 2008;111:5334-5341.