Regulation of immune complex-mediated complement activation by autoantibodies (F-42) isolated from sera of patients with systemic lupus erythematosus.
Sera of some patients with systematic lupus erythematosus (SLE) contain IgG autoantibodies (F-42) which have been shown to stabilize the cell bound classical pathway C3 convertase of complement, C42. C42 is susceptible to inactivation by the plasma protein C4bp while stabilized C42 is relatively resistant to C4bp. The present study demonstrates that F-42 by itself does not induce activation of the classical pathway in vitro but that it is able to modulate the immune complex-induced consumption of C2 and C3 in whole serum. Incubation of incremental concentrations of F-42 with normal human serum (NHS) for 30 min at 30 degrees C did not result in detectable consumption of C1q, C4, C2 and C3. However, when soluble immune aggregates or immune complexes were incubated in NHS together with 100 u/ml of F-42, a significant increase in consumption of C3 was seen as compared to the reaction mixture containing immune complexes or F-42 alone. In addition the presence of F-42 during the immune complex mediated consumption of complement was associated with relative protection of C2 consumption. (Fab)'2 and Fab' fragments of F-42 behaved as intact F-42, except that their activities on a molar basis were less than that of intact F-42. The results presented in this paper suggest that F-42 may play a regulatory role in the immune complex-mediated consumption at C2 and C3 in vivo.
D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D003166:Complement Activating Enzymes / Q000276:immunology; D003167:Complement Activation; D015922:Complement C1q; D003175:Complement C2 / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D003171:Complement Pathway, Classical; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D015922:Complement C1q; D003166:Complement Activating Enzymes