HUMORAL IMMUNE-RESPONSE AND NATURAL-KILLER ACTIVITY IN PATIENTS WITH MIXED CRYOGLOBULINEMIA

Objective. Based opt serological and molecular evidence of hepatitis C virus (HCV) infection in a significant proportion of patients with mi xed cyoglobulinemia (MC), a direct association between HCV and MC has been suggested. The goal of the present study was to investigate the r ole played by HCV and by the immune response to the virus in the patho genesis of mixed cryoglobulinemia. Methods. A competitive reverse tran scription polymerase chain reaction was employed to evaluate the conce ntrations of specific HCV RNA sequences in different clinical specimen s (plasma, sera, cryoprecipitates, bone marrow and peripheral blood ce lls). Using recombinant and synthetic peptides covering the HCV core, envelope I (EI) and nonstructural regions 4 (NS4) and 5 (NS5), the hum oral immune response in a group of MC patients was assessed with an en zyme-linked immunosorbent assay. Natural killer (NK) cell activity was estimated using a 4 hr Cr-51 release assay. Results. Quantitation of the RNA molecules in the biological samples confirmed an increased vir ion concentration in cryoprecipitates from 13/15 patients with mixed c ryoglobulinemia. Analysis of the humoral immune response against the s ynthetic peptides suggested a distinct response to HCV antigens in MC patients when compared to patients with HCV infection but without sero logical evidence of cryoglobulinemia. Unstimulated NK cell functioning was below the normal range in all patients tested. However, periphera l blood mononuclear cells showed no enhancement of NK activity by the interferon inducer polyinosinic acid:polycytidilic acid. Enhancement b y interferon-alpha was normal, suggesting an impairment in interferon production. Conclusion. The quantitative data are in line with the hyp othesis of a direct or indirect role of HCV in mixed cryoglobulinemia. The abnormal immune response could be involved in the onset and persi stence of HCV infection, and possibly in the appearance of cryoglobuli nemia.