A role for hepatitis C virus infection in type II cryoglobulinemia

N Engl J Med. 1992 Nov 19;327(21):1490-5. doi: 10.1056/NEJM199211193272104.


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cryoglobulinemia / etiology*
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / immunology
  • Hepatitis Antibodies / analysis
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Surface Antigens / analysis
  • Hepatitis C / complications*
  • Hepatitis C Antibodies
  • Humans
  • Male
  • RNA, Viral / analysis
  • Rheumatoid Factor / analysis


  • Hepatitis Antibodies
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis C Antibodies
  • RNA, Viral
  • Rheumatoid Factor