Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level.
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, C3b2-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 C3b2-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 C3b2-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.
D001327:Autoimmune Diseases / Q000628:therapy*; D003176:Complement C3 / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000235:genetics*; D003179:Complement C3b / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D003165:Complement System Proteins / Q000187:drug effects / Q000502:physiology*; D003882:Dermatomyositis / Q000097:blood / Q000276:immunology / Q000628:therapy*; D005784:Gene Amplification; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016896:Treatment Outcome
D003176:Complement C3; D003181:Complement C4; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D003179:Complement C3b; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases