HEPATITIS-C VIRUS-INFECTION IN MIXED CRYOGLOBULINEMIA AND B-CELL NON-HODGKINS-LYMPHOMA - EVIDENCE FOR A PATHOGENETIC ROLE

We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglobulinemia (MC) with or without complicating B-cell Non-Hodgkin's lymphoma (NHL) in comparison with other immunolog ical and lymphoproliferative disorders. The following groups of patien ts were studied: A) 25 patients with MC in 7 cases evolved into B-cell NHL; B) 25 healthy subjects; C) 22 patients with different systemic i mmune diseases; D) 24 patients with chronic HCV infection without MC; E) 25 patients with B-cell idiopathic NHL. Methods used included: i) P olymerase chain reaction (PCR) for HCV RNA detection in serum and peri pheral blood mononuclear cells (PBMC) (uncultured or mitogen-stimulate d); ii) Branched DNA (b-DNA) for HCV RNA quantification: iii) HCV geno typing hy genotype-specific primers localized in the core region and b y hybridization of amplification products of the 5' untranslated regio n (5'UTR), obtained with universal primers, using genotype-specific pr obes. Serum anti-HCV and HCV RNA were detected in 88% and 73% of MC pa tients, respectively, and in a significantly lower percentage of healt hy controls and patients with autoimmune diseases. HCV RNA concentrati on was significantly lower in supernatants than in corresponding whole sera (p < 0.001). Plus-strand HCV RNA was detected in 81% of peripher al blood mononuclear cell (PBMC) samples and minus-strand in the major ity of fresh or mitogen stimulated cells. All MC patients with NHL had HCV RNA sequences in PBMC. HCV genotype 2a/III was detected in MC pat ients with a prevalence that was significantly higher than in HCV infe cted patients without MC. Surprisingly, HCV markers (anti-HCV and/or H CV RNA) were found in 32% of patients with idiopathic NHL. These data suggest that HCV infection is involved in the pathogenesis of MC throu gh both direct participation in the immune complex related vasculitis and by triggering the lymphoproliferative disorder underlying the dise ase. This latter disorder seems to be related to HCV lymphotropism whi ch could also be responsible for the evolution of MC to malignant lymp homa. This study also suggests that HCV infection may be involved in t he pathogenesis of idiopathic B-cell NHL through a similar pathogeneti c mechanism.