Long-lasting persistence of large B-cell clones in HCV-cured patients with complete response of mixed cryoglobulinemia vasculitis.

BACKGROUND & AIMS: Hepatitis C virus (HCV)-related mixed cryoglobulinemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor-producing B-cell clones. The aim of this study was to assess whether B-cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes.

METHODS: 45 HCV-cured MCV patients were followed-up for a median of 18.5 (range 9-38) months after the clearance of HCV. Circulating B-cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a VH 1-69-encoded idiotype.

RESULTS: the clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B-cell clones were detected in 18/45 patients, and in 17 of them persisted through the follow-up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV.

CONCLUSION: B-cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These "dormant" cells may be reactivated by events that perturb B-cell homeostasis and can give rise to the relapse of cryoglobulinemic vasculitis. This article is protected by copyright. All rights reserved.