Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals.
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.
Fazi
Claudia
C
Laboratory of B cell Neoplasia, Division of Molecular Oncology, Istituto Scientifico San Raffaele, Milan, Italy.
Dagklis
Antonis
A
Cottini
Francesca
F
Scarfò
Lydia
L
Bertilaccio
Maria Teresa Sabrina
MT
Finazzi
Renato
R
Memoli
Massimo
M
Ghia
Paolo
P
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
D007143:Immunoglobulin Heavy Chains