Clonal B cell populations in the blood and liver of patients with chronic hepatitis C virus infection

Abstract

Objective. The association of hepatitis C virus (HCV) infection with type II mixed cryoglobulinemia is well established, but the role of HCV in B cell lymphoma remains controversial. The objective of this study was to determine the frequency of circulating and liverinfiltrating monoclonal B cells in patients with HCV infection.Methods. One hundred sixty patients were studied prospectively, including 115 HCV-positive patients and 45 HCV-negative patients with other nonimmune chronic liver disease(s). B cell clonality was determined by DNA amplification of the IgH rearrangements, followed by polyacrylamide gel electrophoresis.Results. A clonal B cell population was detected in the blood of 21 (26%) of 81 HCV-positive patients whose cryoglobulin status was known, including 12 of 25 patients with type II cryoglobulinemia, 2 of 12 patients with type III cryoglobulinemia, and 7 of 44 patients without cryoglobulins. A clonal IgH rearrangement was detected in 26 (32%) of 81 liver biopsy specimens from HCV-infected patients, including 16 patients with a circulating clonal population. A clonal B cell population was not observed in the blood of 40 patients with non-HCV liver diseases and was present in only 1 (3%) of 30 liver biopsy specimens. Logistic regression analysis showed that HCV-infected patients with clonal B cell proliferation in both the blood and liver were older (P ‫؍‬ 0.004) and had longer duration of HCV infection (P ‫؍‬ 0.009), higher serum cryoglobulin levels (P ‫؍‬ 0.001) that were more frequently symptomatic (P < 0.03), and liver disease that was more severe than that in patients without a clonal B cell population in the blood or liver (P ‫؍‬ 0.05). In 4 of 16 patients with a clonal B cell population in both the blood and liver, a definite B cell malignancy was finally diagnosed.Conclusion. Clonal B lymphocytes are frequently detected in the blood and liver of patients with chronic HCV infection, in the absence of overt B cell malignancy. These clones are usually, but not always, associated with the presence of type II cryoglobulins. A high percentage of patients with B cell clonality in both the blood and liver were finally diagnosed as having a definite B cell malignancy.

Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

“…In a recent meta-analysis, the prevalence of HCV infection in patients with B-cell non Hodgkin's lymphoma was approximately 15%, which is much higher than the prevalence of HCV in the general population [64] . Clonal B cell proliferation was observed in patients with a longer duration of HCV infection, type Ⅱ cryoglobulin, and vasculitis [5,65,66] . Over 90% patients who developed non-Hodgkin lymphoma had type Ⅱ cryoglobulins [64] .…”

Expansion of Functionally Anergic CD21−/low Marginal Zone-like B Cell Clones in Hepatitis C Virus Infection-Related Autoimmunity

“…Several studies have demonstrated the presence of abnormal clonal B cell populations in the liver and blood of HCV-infected individuals (5)(6)(7)(8). Clonal B cells from patients with HCV-related B cell lymphoproliferation preferentially use the IgH V H 1-69 and Igk V k 3 gene segments, which can encode RF of the WA idiotype (9)(10)(11)(12)(13).…”

Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals

“…In addition to overt clinical manifestations and frank B cell malignancy, HCV affects more generally the B cell compartment in infected individuals, leading to the appearance of monoclonal B lymphocytes in the blood, bone marrow, and liver as revealed by the detection of monoclonal immunoglobulin heavy chain (IGH) gene rearrangements in all these tissues (19)(20)(21)(22)(23).…”