ANTICARDIOLIPIN, ANTI-BETA(2)-GLYCOPROTEIN-I, AND ANTINUCLEOSOME ANTIBODIES IN HEPATITIS-C VIRUS-INFECTION AND MIXED CRYOGLOBULINEMIA

Objective. To investigate anticardiolipin antibodies (aCL), anti-beta( 2)-glycoprotein I (anti-beta(2)GPI), and antinucleosome antibodies in patients with hepatitis C virus (HCV) with or without mixed cryoglobul inemia. aCL can appear in infectious diseases, but are not then associ ated with thrombotic events. Antibodies directed to beta(2)GPI, a co-f actor of aCL, have been said to be associated with the presence of ''a utoimmune'' aCL, About 50% Of cases of essential mixed cryoglobulinemi a are associated with HCV infection, High prevalence of autoantibodies directed to nuclear antigens has been found in HCV infection but the prevalence of antibody to nucleosome has not yet been reported, Method s. Group 1: 29 patients with chronic HCV infection and mixed cryoglobu linemia. Group 2: 17 patients with chronic HCV infection but without m ixed cryoglobulinemia, To analyze the possible effect of mixed cryoglo bulinemia itself on aCL production, we also studied 22 patients with e ssential mixed cryoglobulinemia and no HCV infection (Group 3). In add ition, 96 healthy blood donors were used as a control group (Group 4). Mixed cryoglobulinemia was detected by immunofixation. Anti-HCV antib odies were detected by 3rd generation tests. aCL, anti-beta(2)GPI, and antinucleosome antibodies were detected by ELISA. In patients with mi xed cryoglobulinemia, we also looked for aCL separately in cryoprecipi tate and in serum after extraction of mixed cryoglobulins to investiga te a possible ''capture'' of aCL in the cryoprecipitate. Results. IgG aCL were more frequently found in patients with HCV than in controls [ 9/46 (20%) vs 2/96 (2%); p < 0.001]. The prevalence of aCL was similar in patients with HCV with or without mixed cryoglobulinemia (6/29 vs 3/17; p = NS). No patient with positive aCL had anti-beta(2)GPI, anti- nucleosome antibodies, thrombotic events, or thrombocytopenia, IgG aCL were more frequent in patients with mixed cryoglobulinemia, whatever their status for HCV infection, than in subjects without mixed cryoglo bulinemia [8/51 (16%) vs 5/113 (4%); p < 0.02]. The prevalence of aCL was similar in patients with type II or type III mixed cryoglobulinemi a. When we looked for aCL separately in serum and in cryoprecipitate, we did not find aCL in cryoprecipitate. In patients with HCV, the prev alence of aCL was not different whether patients were treated or not w ith interferon alpha. Conclusion. IgG aCL are frequently found in pati ents with HCV regardless of status for mixed cryoglobulinemia. These a CL have the characteristics of infection related aCL, low titer, absen ce of thrombotic events, and absence of anti-beta(2)GPI. The high prop ortion of aCL in patients with mixed cryoglobulinemia compared to thos e without, and the absence of antinucleosome antibodies, suggest that these aCL may be secondary to endothelial damage induced by mixed cryo globulinemia or HCV itself, rather than to nonspecific polyclonal lymp hocyte activation.