title: Detection of WA B cells in hepatitis C virus infection: a potential prognostic marker for cryoglobulinemic vasculitis and B cell malignancies.
abstract: OBJECTIVE
  An uncommon manifestation of hepatitis C virus (HCV) infection is systemic vasculitis associated with type II cryoglobulinemia (cryoglobulinemic vasculitis), a proliferative B cell disorder that transforms into B cell malignancy in 5-10% of patients. The monoclonal rheumatoid factors (mRF) that bear the WA cross-idiotype (Xid) are responsible for most cases of cryoglobulinemic vasculitis in patients with HCV infection. The purpose of this study was to determine whether WA B cells can be detected in asymptomatic patients with HCV infection, using sequence analysis of B cell clonal expansions (BCEs) to identify the WA Xid.
  
  
  METHODS
  Asymptomatic patients with HCV infection and those without HCV infection as well as respective control patients with cryoglobulinemic vasculitis, whose serum was either negative or positive for WA mRF, were studied. BCEs were isolated in the patients' blood, and WA BCEs were identified by sequencing analysis.
  
  
  RESULTS
  BCEs were detected in all control patients with cryoglobulinemic vasculitis, but only control patients with HCV infection had WA BCEs. None of the 33 asymptomatic patients without HCV infection had a BCE. WA BCEs were detected in 4 (7.4%) of 55 asymptomatic patients with HCV infection, in none of 14 patients with HCV infection and type III cryoglobulinemia, and in 5 (13.5%) of 37 patients with HCV infection and serum RF positivity. One patient with a WA BCE had splenic lymphoma markers and villous lymphocytes, and the villous lymphocytes were found to be WA B cells.
  
  
  CONCLUSIONS
  By identification of the WA Xid, WA B cells can be detected in asymptomatic HCV-infected patients. WA B cells in asymptomatic patients with HCV infection may be a marker for the development of cryoglobulinemic vasculitis and associated B cell malignancies. The results of this study provide a basis for the development of the first practical clinical application of cross-idiotype analysis.
authors.affiliation: Lahey Clinic, Burlington, Massachusetts 01805, USA.
authors.forename: Glenn B
authors.initials: GB
authors.lastname: Knight
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Laura
authors.initials: L
authors.lastname: Gragnani
authors.forename: Mutasim M
authors.initials: MM
authors.lastname: Elfahal
authors.forename: Francesco G
authors.initials: FG
authors.lastname: De Rosa
authors.forename: Fredric D
authors.initials: FD
authors.lastname: Gordon
authors.forename: Vincent
authors.initials: V
authors.lastname: Agnello
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000276:immunology; D003449:Cryoglobulinemia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D005803:Genes, Immunoglobulin; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D015448:Leukemia, B-Cell; D016393:Lymphoma, B-Cell; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014657:Vasculitis / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D007130:Immunoglobulin Idiotypes