HIGH-DOSES OF IMMUNOGLOBULIN-G ATTENUATE IMMUNE AGGREGATE-MEDIATED COMPLEMENT ACTIVATION BY ENHANCING PHYSIOLOGICAL CLEAVAGE OF C3B IN C3B(N)-IGG COMPLEXES

Intravenously applied human IgG has beneficial effects in treating inf lammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activatio n and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates, IgG added at 2 to 10 mg/ml. stimulated the physiologic inactivation of C3b-containing complexes t wofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-c ontaining complexes., Exogenous IgG (5 mg/mL) also stimulated inactiva tion of purified C3b(2)-lgG complexes, whereby their half-life dropped from 3-4 to 1,5 minutes in 20% serum, IgG appeared to act like a modu lator of factor H and I because it did not stimulate inactivation of C 3b-containing complexes in factor I-deficient serum, Thus, the known p artial protection of C3b(n)-lgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG, The ability o f high doses of IgG to stimulate complement inactivation is a novel re gulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations , (C) 1996 by The American Society of Hematology.