Mixed cryoglobulinaemia, immunoglobulin heavy chain (IgH) rearrangement and activation of nuclear factor kappa B (NFkB) in chronic hepatitis C virus (HCV) infection

B Gasztonyi, MD,^a A Par,MD PhD,^a K Kiss, MD,^b L Kereskai,MD,^c J Szeberenyi, MD PhD,^b L Pajor,MD PhD,^c G Hegedus,MD,^d Gy Mozsik, MD ScD^a

Background: Hepatitis C virus (HCV) infection may have a pathogenetic role in both mixed cryoglobulinaemia (MC) and development of B-cell non-Hodgkin lymphoma (NHL). Aims: Prevalence of MC was determined in patients with chronic hepatitis C and immunoglobulin heavy chain (IgH) rearrangement was studied to verify the clonality of lymphoproliferation in HCV infected patients. In addition, activation of nuclear factor kappa B (NFkB) was investigated in peripheral blood lymphocytes. Patients and methods: A total of 90 patients with chronic HCV infection have been studied for MC and IgH rearrangement. Ten patients with chronic hepatitis C, 13 patients with B-cell NHL (among them 4 HCV positive) and 10 healthy subjects were examined for the activity of NFkB transcription factor using electrophoretic mobility shift assay (EMSA). Results: MC was detected in 22/90 (24.4 %) patients, IgH rearrangement occurred in 14/90 patients (15.5 %), 7 of them suffering from MC. NFkB specific oligonucleotide-protein complexes have been found in the lymphocyte extracts from 8/10 patients with chronic hepatitis C and in 10/13 patients with B-cell NHL. Conclusions: IgH gene rearrangement is sensitive method for detecting occurrence of early stage of B-cell lymphoproliferative disease in HCV infection. Cryoglobulinaemia can be an intermediate step in HCV-related B-cell proliferation and NHL. NFkB activation was shown in chronic hepatitits C similarly as that in B-cell NHL. Our findings support the hypothesis, that HCV plays an etiological role in the lymphoproliferation leading to B-cell NHL.

KEY WORDS: Hepatitis C virus, B-cell non-Hodgkin’s lymphoma, NFkB.

For more information, contact gasztonyi@clinics.pote.hu

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Viral Oncogenesis.

http://www.cancerprev.org/Journal/Issues/26/101/996/4354