title: Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals.
abstract: BACKGROUND
  Monoclonal B cell lymphocytosis (MBL) is a preclinical condition characterized by an expansion of clonal B cells in the absence of B lymphocytosis (BALC < 5 × 10(9)/L) in the peripheral blood, without clinical signs, suggestive of a lymphoproliferative disorder. B cell clonal expansions are also associated with hepatitis C virus (HCV) infection and they can evolve into lymphoproliferative disorders such as mixed cryoglobulinemia and non-Hodgkin lymphomas (NHL). The relationship between MBL and HCV infection has not been established yet.
  
  
  METHODS
  By five-colour flow cytometry, we analyzed 123 HCV positive subjects with diagnosis of chronic hepatitis (94) or cirrhosis (29); 16 of those with cirrhosis had a diagnosis of hepatocellular carcinoma.
  
  
  RESULTS
  MBL were identified in 35/123 (28.5%), at significantly higher frequency than in the general population. Sixteen/thirty-five were atypical-chronic lymphocytic leukemia (CLL) MBL (CD5(+), CD20(bright)), 13/35 were CLL-like MBL (CD5(bright), CD20(dim)), and 6/35 were CD5(-) MBL. Twenty-four/ninety-four (25.5%) patients affected by chronic hepatitis had MBL, whereas 11/29 (37.9%) patients with cirrhosis showed a B cell clone. A biased usage of IGHVgenes similar to HCV-associated NHL was evident.
  
  
  CONCLUSIONS
  All three types of MBL can be identified in HCV-infected individuals at a higher frequency than in the general population, and their presence appears to correlate with a more advanced disease stage. The phenotypic heterogeneity is reminiscent of the diversity of NHL arising in the context of HCV infection. The persistence of HCV may be responsible for the dysregulation of the immune system and in particular of the B cell compartment.
authors.affiliation: Laboratory of B cell Neoplasia, Division of Molecular Oncology, Istituto Scientifico San Raffaele, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fazi
authors.forename: Antonis
authors.initials: A
authors.lastname: Dagklis
authors.forename: Francesca
authors.initials: F
authors.lastname: Cottini
authors.forename: Lydia
authors.initials: L
authors.lastname: Scarfò
authors.forename: Maria Teresa Sabrina
authors.initials: MT
authors.lastname: Bertilaccio
authors.forename: Renato
authors.initials: R
authors.lastname: Finazzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Memoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000209:etiology / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D007964:Leukocytosis / Q000209:etiology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology*; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains