Treatment of erythrocytes with the thiolspecific oxidant azodicarboxylic acid bis(dimethylamide) (diamide) enhances their phagocytosis by adherent monocytes. Phagocytosis of diamide-treated erythrocytes required that the cells were opsonized with whole serum, since complement inactivation abolished phagocytosis. Opsonization with whole serum containing 20-100 times the physiological concentration of naturally occurring anti-band-3 antibodies enhanced phagocytosis of diamide-treated erythrocytes. High inputs of antiband-3 also restored phagocytosis oferythrocytes that had been incubated with complement-inactivated serum. Elevated concentrations of anti-spectrin antibodies were ineffective in whole and complement-inactivated serum.

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Intravenously applied normal human immunoglobulin G (IgG) has anti-inflammatory effects in the treatment of autoimmune diseases. Systemic inflammation can originate from an overreacting amplification loop of the complement system. In blood, C3b 2 -containing complexes maintain complement amplification much better than the extremely short-lived C3b. Therefore, in patients with the complement-dependent autoimmune disease, dermatomyositis, we studied whether intravenously applied normal human IgG (IVIG) stimulated in vivo inactivation of these complexes. In the course of IVIG treatment, clinically effective in 6 of 8 patients, the concentration of C3b 2 -containing complexes dropped to 37% ؎ 14% (n ‫؍‬ 6) of the pretreatment level when having infused 0.5 g IgG/kg body weight, increased marginally and in parallel to factor Bb thereafter until full-dose IgG was infused. By day 14 following infusion of 2 g IgG/kg body weight the concentration of C3b 2 -containing complexes was 66% ؎ 19%. The plasma concentration of C3 remained constant in myopathic or increased by 15% to 20% in amyopathic patients. In contrast to this, IVIG infusion was associated with consumption of up to 40% of plasma C4 at day 1 to 2 after completion of IVIG infusion. Thus, IVIG had an immediate and long-lasting attenuating effect on complement amplification in vivo, despite the fact that it induced classical complement pathway activation. IntroductionIntravenously applied human immunoglobulin G (IgG) has an immunomodulatory potential. 1 This effect might in part be due to modulation of phagocytic cells either by altering autocrine or paracrine cytokines through the action of anticytokine antibodies 2,3 or alterations of cell receptor functions 4 or expression. 5,6 Intravenously applied human IgG (IVIG) is, however, similarly beneficial in autoimmune diseases that are associated with excessive complement activation via the classical pathway and the amplification loop. [7][8][9] Such complement activation is proinflammatory by generating C3b in excess. C3b, the active form of C3, binds covalently to targets and promotes generation of C3 convertases, which, in turn, consume C3 and allow assembly of C5 convertase. Elevated C3/C5 convertase activity 10 produces locally proinflammatory anaphylatoxins, C3a/C5a, and generates C5b that can initiate formation of the membrane attack complex on target cells. Finally, insertion of C5b to 7 and C9 into membranes of nucleated cells can result in activation of the arachidonic acid pathway that forms mediators of inflammation. 11 IVIG at high doses is able to displace nascent C3b from tissue-bound immune complexes to the fluid phase 12,13 by serving as a preferential binding site for C3b. 14 Although this process reduces local complement activation, it does not stop systemic complement amplification. Indeed, nascent C3b deposited to fluid-phase IgG primarily forms C3b 2 -IgG complexes. 14 These complexes represent potent activators of the amplification loop and are, on a molar basis, more efficient activators tha...