The interaction of immune serum globulin and immune globulin intravenous with complement.
The in vitro anticomplementary activity of untreated and heat-aggregated (63 degrees C, 10 min) immune serum globulin (ISG) and immune globulin intravenous (IGIV) prepared by partial reduction and alkylation have been evaluated by three assays, C3 activation, binding to C1q and enhancement of alternative pathway lysis of rabbit erythrocytes. Crossed immunoelectrophoresis was used to quantitatively measure the ability of ISG and IGIV to activate endogenous C3 in normal serum. Binding to C1q was determined according to the ability to inhibit binding of 125I-C1q to solid phase IgG. ISG and IGIV enhancement of lysis of rabbit erythrocytes by normal human serum adsorbed with rabbit erythrocytes in the presence of MgEGTA was used to determine activity in the alternative complement pathway. Unheated IGIV at 10 mg/ml only marginally activated endogenous C3 in normal serum, had about a 5-fold lower affinity for 125I-C1q (Ki = 138 to 356 microM vs Ki = 62.5 microM for ISG), but was very similar in ability to ISG on a weight basis in enhancing complement alternative pathway activity (RCH50 = 0.23 to 0.40 mg for IGIV vs 0.17 mg for ISG). Heat-aggregated IGIV at 5 mg/ml in normal human serum was about 2-fold less effective than heat-aggregated ISG in the activation of C3 in normal serum and had approximately 2- to 3-fold lower affinity in the C1q binding assay (Ki = 45 to 83 nM for heat-aggregated IGIV vs Ki = 14.6 nM for heat-aggregated ISG). These data suggest that IGIV prepared by chemical modification retains sufficient specific receptor activity to allow in vivo efficacy in complement-mediated amplification of host defense reactions, but is safe for intravenous use due to a lower capacity to initiate nonspecific complement activation.
D003166:Complement Activating Enzymes / Q000378:metabolism; D003167:Complement Activation; D015922:Complement C1q; D003176:Complement C3 / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000276:immunology; D006358:Hot Temperature; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007136:Immunoglobulins / Q000008:administration & dosage / Q000276:immunology*; D007275:Injections, Intravenous
D003176:Complement C3; D007136:Immunoglobulins; D015922:Complement C1q; D003165:Complement System Proteins; D003166:Complement Activating Enzymes