INHIBITION OF 125I-C3 UPTAKE ANH HEMOLYTIC COMPLEMENT ACTIVITY BY IV IgG

Abstract

Listen

Translate article

Recent studies suggest that IgG is a particularly good acceptor for nascent C3b. We used therapeutic immune serum globulin (ISG) preparations to determine if excess IgG would compete for deposition of C3b onto activators such as antibody sensitized sheep erythrocytes (EA) and decrease hemolytic activity. Both im and iv forms of ISG inhibited uptake of 125I-C3 onto EA with C6 or C8 deficient sera as sources of early complement components. 125I-C3 uptake was inhibited 50% at 10-20 mg/ml of im ISG and 20-30 mg/ml of iv ISG (Cutter). Similar concentrations of ISG also inhibited 125I-C3 uptake onto preformed EAC 14 with the deficient sera or with purified C2. IV and im ISG inhibited hemolytic activity of whole serum with EA and of purified C3 with EAC 14 and purified components, but the concentrations necessary for 50% inhibition of the hemolytic assays were much lower. These effects of IgG were specific since addition of human serum albumin at equivalent concentrations did not inhibit any of the assays. Using ISG fractionated by gel filtration, we verified that the inhibition of hemolytic activity was due to monomeric IgG rather than aggregates. These results suggest that inhibition of C3 uptake onto particles can occur at the elevated serum IgG levels achieved during high dose IVIG therapy. Diminished uptake of C3 onto sensizitzed platelets could contribute to the efficacy of high dose IVIG in ITP.