Hepatitis C virus (HCV) infection can lead to B-cell malignancy via direct infection and transformation of B-lymphocytes, or via indirect transformation by chronic antigen-driven stimulation. Both mechanisms may occur simultaneously, as we previously reported in a case of HCV infection followed by plasma-cell leukemia (PCL), where blasts were infected with HCV and the monoclonal immunoglobulin (Ig) they produced was directed against the core protein of the virus (

New Engl J Med, 2003; 348:178
). Approximately 10% of HCV-positive patients develop a monoclonal Ig, the specificity of which is usually unknown. To evaluate the link between chronic HCV-antigen driven stimulation and plasma–cell transformation, we studied the specificity of monoclonal Ig developed in the context of HCV infection. Over a period of 13 months, sera from patients consulting or hospitalised at the Centre Hospitalier Universitaire of Nantes found positive for monoclonal Ig, were systematically tested for the presence of HCV RNA and anti-HCV Ig. Among the 700 patients thus studied, 10 (1.4%) were found positive for HCV. Purification of the monoclonal Ig was achieved for 7/10 patients. Using immunoblotting, the purified monoclonal Ig (2 IgG, 1 IgA, 1 IgM) of 4 patients, all with HCV genotype 2, recognized the C22–3 fragment of HCV-core protein; 2 (IgG) recognized NS-4 and 1 did not recognize HCV. Among the 4 patients with anti-HCV-core monoclonal Ig, two presented with mixed (type II) cryoglobulinemia and one was diagnosed with multiple myeloma. Hence, 2/5 patients with anti-HCV core monoclonal Ig developed plasma-cell malignancy. Anti-HCV treatment resulted in the disappearance of the monoclonal Ig for 3/3 treated patients. In summary, in the context of HCV infection monoclonal Ig were typically directed against the virus, and could distinguish patients with increased risk of plasma-cell malignancy. Efforts should be made to identify such patients, as anti-viral therapy should help eradicate the HCV-driven plasma-cell clone.

Topics:
cancer, hepatitis c virus, infections, monoclonal immunoglobulin, plasma cells, immunoglobulins, hepatitis c, hepatitis c antibodies, antigens, immunoglobulin g

Disclosures: No relevant conflicts of interest to declare.

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2008, The American Society of Hematology
2008
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