• HCV;
  • mixed cryoglobulinaemia;
  • IgM;
  • B-lympho-cytes;
  • clonal expansions

Summary. 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 Waldenstrom's disease), one with type III mixed cryoglobulinaemia, one with Waldenstrom'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 poly-acrylamide 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.