Relationship between rheumatoid factor and the immune response against hepatitis C virus in essential mixed cryoglobulinemia

Objective. The authors examine the relationship between the presence of hepatitis C virus (HCV) and anti-HCV antibodies, rheumatoid factor (RF) activity, the level of complement, and the cryocrit in the sera of patients affected by essential mixed cryoglobulinemia (EMC). In addition, the authors evaluate the circulating B-CD5 positive lymphocytes, believed to be RF producers in the blood of EMC patients. Methods. Clinical and laboratory data on 219 cases of EMC were collected from five centers of the GISC (Italian Group for the Study of Cryoglobulinemias). Statistical analyses of these data were carried out with the aim of evidentiating significant relationships, in order to shed light on the mechanism of cryoprecipitation. Results. The cryocrit was higher in anti-HCV negative and in HCV-RNA positive sera. The titers ofRF activity were significantly higher in anti-HCV negative sera. A linear correlation between RF activity and the cryocrit was observed for HCV-RNA positive cases (r = 0.416), this correlation being highest in the patients who were HCV-RNA positive and anti-HCV negative (0.709). Type III EMC were more reactive than type II against the non-structural antigens of HCV, particularly 5-1-1 and C-22. There were more circulating B lymphocytes sharing membrane antigen CD5 in EMC than in the blood of normals or patients with HCV-related chronic hepatitis. Levels of circulating B-CD5 correlated with serum RF activity (r = 0.677), especially in sera from anti-C-100 negative patients (p = 0.991). Conclusion. The data strongly suggest that the level of the cryoprecipitate is a function of both the HCV-RNA in the serum and the RF activity. Antibody specificity against HCV probably influences the density of the cryoprecipitate.