Cold activation of serum complement in patients with chronic hepatitis C: Study on activating pathway and involvement of IgG

It has been documented that the serum complement activities measured by hem olytic assay (CH50) are decreased after storage of sera at a low temperatur e in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factor s involved in the cold activation of complement (CAC). To clarify what path way is activated in CAC, we measured complement cleavage products after col d storage of sera. C4d increased significantly after 12 h-storage at cold t emperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 cont rol sera (P < 0.05), while Bb did not increase in any of the groups. In ord er to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them ret ained hemolytic activities to some extent after cold storage. Column chroma tography through Superose 6HR of CAC-positive serum identified the fraction s containing molecules that induced CAC in normal serum, which were deplete d by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produ ced in hepatitis C virus infection may be an important factor in inducing C AC, a common extrahepatic manifestation of hepatitis C.