Recovery of Hepatitis C Specific T-cell Responses after Rituximab Therapy in Hepatitis C Mixed Cryoglobulinemic Vasculitis

Abstract

Background & Aims: Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV-specific T cell phenotype and function.

Methods: Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375mg/m²) and variables were measured 6 months after therapy. Using flow cytometry and Enzyme-Linked Immunospot assay, the number of activated and tissue-like B cells and number of T cells expressing Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and multiple cytokines were measured before and after rituximab therapy.

Results: B cell depletion therapy is associated with a significant (P<0.0001) decline in peripheral T cells with exhaustive phenotype, from pre-therapy to post-therapy-of rituximab (mean±standard error): CD4+ (16.9±0.9% to 8.9±1.0%) and CD8+ (6.8±0.6% to 3.0±0.5%) T cells expressing PD-1 and CD4+ (11.0±1.0% to 6.1±0.8%) and CD8+ (12.7±0.7% to 6.4±0.4%) T cells expressing TIM-3. In addition, there was a significantly higher percentage of peripheral CD8+ T cells responding to HCV peptide stimulation in vitro secreting IFN-γ (4.55±0.3 to 9.6±1.0 IFN-γ/10⁶ PBMCs, P<0.0001), and more than one cytokine (1.3±0.1% to 3.8±0.2%, P<0.0001) after therapy compared to pre-therapy.

Conclusion: B cell depletion therapy results in recovery of T cell exhaustion and function in patients with HCV cryoglobulinemic vasculitis. This article is protected by copyright. All rights reserved

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