Hepatitis C virus and immunoglobulin gene rearrangements: an early step in lymphomagenesis?

A clonal expansion of peripheral blood mononuclear cells committed to IgM cryoprecipitating rheumatoid factor production has been demonstrated in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC). To determine the role of HCV in B cell gene rearrangements we studied a series of 57 HCV-infected patients with and without MC. Clonal Ig gene rearrangements of both RNA and DNA were detected in 10 of the 13 patients with type II MC, 1 patient had gene rearrangement of the DNA only, and 2 had polyclonal patterns. 2 of the 17 patients with type III MC showed clonal rearrangement of both RNA and DNA, in 6 only the DNA was rearranged clonally and in 9 the patterns were completely normal. 14 of 27 patients with cryocrit <1% or without cryoglobulins had clonal DNA rearrangements without any in the RNA. These results suggest that clonal lesions in the DNA are related to HCV infection and that these changes antedate the appearance of mixed cryoglobulinemia.