Clonal B‐cell expansions in peripheral blood of HCV‐infected patients

Abstract

Clonal expansions of IgM-producing B cells were investigated in 38 patients with a chronic hepatitis C virus infection. Eight patients were affected with type II mixed cryoglobulinaemia (two of whom also had non-Hodgkin's lymphoma and one had Waldenström's disease), one with type III mixed cryoglobulinaemia, one with Waldenström's disease, and 28 with chronic liver disease. To detect the clonal B-cell expansions we used a RT/PCR procedure in which the CDR3/FW4 regions of the IgM heavy chain mRNAs were amplified and resolved in sequencing polyacrylamide gels. Clonal Ig gene rearrangements were detected in all patients with type II mixed cryoglobulinaemia and also at a high frequency (24%) in the HCV-infected patients without cryoglobulinaemia. A polyclonal pattern was present in the patient with type III mixed cryoglobulinaemia and in the 15 normal individuals and 16 age-related patients with HCV-negative alcoholic liver disease which were investigated as controls. No association was found between the presence of a clonal B-cell expansion and age, sex, liver histology, or levels of serum aminotransferase. The serum levels of rheumatoid factor were increased in all patients with a clonal expansion, suggesting that the expanded B-cell clones belong to the rheumatoid factor producing B-cell subset.

Peripheral B-cell CD5 expansion and CD81 overexpression and their association with disease severity and autoimmune markers in chronic hepatitis C virus infection

“…The pathogenetic link between HCV and the immune system in inducing both autoimmunity and lymphproliferation is unclear. The persistence of HCV in peripheral blood mononuclear cells, preferentially in B-cells [15], results in chronic stimulation of B-cells, leading to polyclonal and later to monoclonal proliferation of RF (IgMk)-producing cells, which may result eventually in malignant transformation and development of overt lymphoma [16][17][18][19]. The recent identification of CD81 protein as one of the HCV receptor candidates on B-lymphocytes [20] provides a mechanism by which B cells are infected with or activated by HCV and may raise a wide spectrum of interesting issues regarding the pathogenetic link between HCV infection, autoimmunity and lymphoproliferative disorders.…”

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).…”

Hepatitis C virus-related lymphoproliferative disorders encompass a broader clinical and morphological spectrum than previously recognized: a clinicopathological study

“…This observation confirms and expands previous descriptions of clonal B-cell population in the blood of HCV-infected persons, as well as clonal B-cell infiltrates in the bone marrow and liver biopsies of patients with HCV infection, associated or not with cryoglobulinemia. [22][23][24][25][26] These infiltrates were shown to remain unmodified during a long follow-up in most cases but can be followed up as overt lymphoma in about 10% of them. The term 'monotypic lymphoproliferative disorder of undetermined significance' 1 has been proposed for these cases.…”