A Role for Hepatitis C Virus Infection in Type II Cryoglobulinemia

Abstract

Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors, the cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected. We studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV infection. Quantitative HCV antibody and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Eight patients (42 percent) had HCV antibodies, and 16 (84 percent) had HCV RNA. Of the 19 patients, 5 (26 percent) had HBV markers, but only 1 had evidence of active HBV infection. Control serum samples from nine patients with Type I cryoglobulinemia were negative for HCV antibody and HCV RNA. There was a close, although not exclusive, association of one type of rheumatoid factor (WA) with HCV RNA. HCV antibody and HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in the Type II cryoglobulins examined. Type II cryoglobulinemia is strongly associated with concomitant HCV infection and a high rate of false negative serologic tests. HCV virions and HCV antigen-antibody complexes are concentrated in the cryoprecipitates, most commonly in association with the WA type of rheumatoid factor, suggesting a role for HCV in the pathogenesis of mixed cryoglobulinemia. (N Engl J Med 1992;327:1490–5.), THE manifestations of mixed cryoglobulinemia range from mild vasculitis, with the characteristic palpable purpura, arthralgias, and weakness, to severe vasculitis, with involvement of the kidneys, nerves, and brain.1,2 Serologically, cryoglobulins are classified into three types3: Type I consists of monoclonal immunoglobulins without rheumatoid factor activity that are predominantly associated with malignant conditions of the immune system; Types II and III are mixed cryoglobulins. Type II consists of polyclonal IgG and monoclonal IgM rheumatoid factors. In Type III, both the IgG and rheumatoid factors are polyclonal. Clinically, mixed cryoglobulinemia has been classified as essential if there is no primary disease… © 1992, Massachusetts Medical Society. All rights reserved.