The mechanism of effect of high-dose intravenous immunoglobulin (IVIG) therapy in immune cytopenias is incompletely known. One of the leading theories ascribes the short-term effects of IVIG to the competition of infused IVIG for Fc receptors, thereby inhibiting IgG-mediated clearance. Using a system independent of IgG-Fc receptor interactions, we examined another potential mechanism of IVIG action. Guinea pigs were infused with a human IVIG preparation at 600 mg/kg/day for two consecutive days. Parallel groups of animals were treated with the same volume and/or concentration of saline and albumin. Clearance of IgM- sensitized guinea pig erythrocytes, which is wholly complement dependent, was significantly retarded in animals treated with high-dose IVIG. The effect was specific for IVIG, since human albumin (as a second foreign protein) failed to change the clearance of IgM- sensitized guinea pig erythrocytes. Experiments in which IVIG-treated animals were subjected to pre- and posttreatment clearance studies revealed heterogeneity among individual animals in respect to their response to IVIG infusions. Decrease of available plasma complement components did not account for the effect, since both C3 and CH50 values remained unchanged after IVIG treatment, despite rising levels of IVIG in sera of treated animals. The results of in vitro C3 uptake studies and the effect of IVIG on clearance of preopsonized cells suggest that IVIG produces a kinetic depression of C3 uptake and modifies the process of complement fragment deposition on erythrocytes. A generalized effect on mononuclear phagocytes is less likely but cannot be wholly ruled out. These studies establish another potential mechanism of IVIG action and suggest extension of its use to other complement-mediated diseases.

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Extensive studies have been conducted to determine the pathogenesis of the adult respiratory distress syndrome (ARDS) by investigating the role of complement, a mediator of inflammation. Complement activation products have been detected in blood samples from patients during ARDS. However, the individual complement components that have been assessed only indicated generalized inflammation, and none could unequivocally discriminate the onset of this acute inflammatory lung injury. In this two-year prospective study of 87 septic patients, 22 of whom developed ARDS (25%), we determined complement activation by quantifying the terminal complement complex (TCC), C5b-9. The TCC is a stable complement by-product formed following activation of either the classical or alternative pathways. Our results show that plasma TCC concentrations increased an average of 110% (p = 0.002) two days prior to the onset of ARDS and also transiently increased an average of 45% (p = 0.01) immediately preceding its resolution. Furthermore, plasma TCC concentrations were a more sensitive measure of this acute inflammatory lung injury than levels of C3a desarginine, C4a desarginine, C5a desarginine, and total hemolytic complement activity. We conclude that a temporal association exists between accentuated formation of plasma TCC and the development and also resolution of septic ARDS. Therefore, we suggest that researchers include plasma TCC concentrations in clinical studies when they could use a potential early indicator for ARDS.

Concentrations of the terminal complement complex (TCC), C5b-9, were examined in 120 serum samples from 28 patients with systemic lupus erythematosus. Eleven patients with various manifestations of the disease were followed longitudinally for a 2-year period during active and inactive phases of the disease. In 9 of the 11 patients, elevations in TCC concentrations correlated with disease exacerbations. In many of these patients, C3 and C4 levels remained normal during the study and were less sensitive indicators of disease activity than were TCC concentrations. We believe that measurements of TCC are useful in monitoring patients with rheumatic diseases in which complement activation is a component.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by multiple exacerbations and remissions; its cause is not known. Although many studies have concentrated on renal disease in SLE, which results from the deposition of immune complexes in the kidney, other organs are also involved, including the joints, skin, blood, brain, lungs, and heart (1).Serologic abnormalities in patients with SLE