Hepatitis C virus and immunoglobulin gene rearrangements: An early step inlymphomagenesis?

A clonal expansion of peripheral blood mononuclear cells committed to IgM c ryoprecipitating rheumatoid factor production has been demonstrated in hepa titis C virus (HCV)-associated mixed cryoglobulinemia (MC). To determine th e role of HCV in B cell gene rearrangements we studied a series of 57 HCV-i nfected 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 pati ent 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 R NA and DNA, in 6 only the DNA was rearranged clonally and in 9 the patterns were completly normal. 14 of 27 patients with cryocrit <1% or without cryo globulins had clonal DNA rearrangements without any in the RNA. These resul ts suggest that clonal lesions in the DNA are related to HCV infection and that these changes antedate the appearance of mixed cryoglobulinemia.