title: Hepatitis B virus causes mixed cryoglobulinaemia by driving clonal expansion of innate B-cells producing a VH1-69-encoded antibody.
abstract: OBJECTIVE
  To investigate the expression of a VH1-69-encoded idiotype, and the phenotypic and functional features of monoclonal B-cells from patients with type II mixed cryoglobulinaemia (MC) secondary to chronic hepatitis B virus (HBV) infection.
  
  
  METHODS
  B-cell immunophenotype and expression of a VH1-69-encoded idiotype were investigated by flow cytometry. B-cell proliferative responses to stimuli were investigated by the CFSE dilution assay.
  
  
  RESULTS
  Two out of five patients with chronic HBV studied had massive monoclonal expansion of VH1-69-expressing B-cells. These cells had the peculiar CD21(low) phenotype and low responsiveness to stimuli typical of the VH1-69-expressing B-cells commonly expanded in MC secondary to hepatitis C virus (HCV) infection. In both patients, anti-HBV therapy led to the regression of MC and of VH1-69+ B-cell expansion.
  
  
  CONCLUSIONS
  VH1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including HCV E2, influenza A virus haemagglutinin and HIV gp41/gp120, and may serve as innate first line antiviral defense. Thus, like HCV, HBV may cause MC by protracted antigenic stimulation of VH1-69-expressing B-cells.
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy. marcella.visentini@uniroma1.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pascolini
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Milica
authors.initials: M
authors.lastname: Mitrevski
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Ramona
authors.initials: R
authors.lastname: Marrapodi
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Del Padre
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Todi
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Camponeschi
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Axiotis
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Carlesimo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: De Santis
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.affiliation: Division of Clinical Immunology, Department of Clinical Medicine, Sapienza University of Rome, Italy.
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003449:Cryoglobulinemia / Q000209:etiology*; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D007113:Immunity, Innate; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008297:Male; D008875:Middle Aged
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region