HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN DOES NOT AFFECT COMPLEMENT-BACTERIA INTERACTIONS

Pooled IgG preparations for i.v. use (IVIg) have been shown to possess anticomplementary activity in autoimmune and systemic inflammatory di seases. Both in vitro and in vivo, IVIg is a preferential acceptor of activated C4 and C3, thus diverting complement activation from the tar get surface. We explored the effect of IVIg on complement-bacteria int eractions in an attempt both to determine the safety of IVIg preparati ons in relation to natural immunity to bacteria and to extend our know ledge of the physiologic mechanism of action of IVIg. Using both compl ement-sensitive and complement-resistant bacterial strains, we investi gated the effect of IVIg on C3 binding to bacterial surfaces. In all c ases, whether complement could be directly activated by bacteria throu gh the classical or the alternative pathway, IVIg had no effect on the amount of C3 bound to bacteria, In addition, IVIg did not inhibit com plement-dependent bacterial lysis. Interestingly, increasing concentra tions of IVIg induced an increase in Clq binding, suggesting the prese nce of low affinity complement-fixing antibacterial Abs in certain pre parations. Using serum samples from patients treated with IVIg complem ent binding to and lysis of complement-sensitive bacterial strains wer e not modified as compared with normal controls and pretreatment sampl es, although a decrease in C3 binding to sensitized human erythrocytes was observed. Our data suggest that IVIg does not affect direct compl ement-bacteria interactions, although it is a potent agent to use for diversion of complement activation on sensitized target surfaces.