Long-lasting persistence of large B-cell clones in hepatitis C virus-cured patients with complete response of mixed cryoglobulinaemia vasculitis

Liver Int. 2019 Apr;39(4):628-632. doi: 10.1111/liv.14053. Epub 2019 Feb 15.

Abstract

Background & aims: Hepatitis C virus (HCV)-related mixed cryoglobulinaemia 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: Forty-five 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 of 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.

Conclusions: 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 cryoglobulinaemic vasculitis.

Keywords: B-cell clone; Hepatitis C virus; direct-acting antivirals; mixed cryoglobulinaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • B-Lymphocytes / immunology*
  • Clone Cells / immunology
  • Cryoglobulinemia / immunology*
  • Cryoglobulinemia / virology
  • Female
  • Flow Cytometry
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy
  • Humans
  • Male
  • Middle Aged
  • Vasculitis / immunology*
  • Vasculitis / virology

Substances

  • Antiviral Agents