Complement system on the attack in autoimmunity

Abstract

The antiphospholipid syndrome is characterized clinically by fetal loss and thrombosis and serologically by the presence of autoantibodies to lipid-binding proteins. In a model of this procoagulant condition in which these antibodies are injected into pregnant mice, fetal loss was prevented by blocking of complement activation. Specifically, interaction of complement component 5a (C5a) with its receptor is necessary for thrombosis of placental vasculature. Inhibition of complement activation may have a therapeutic role in this disease.

Figure 1

C3b can be deposited on a target by immune complexes that commonly engage the classical pathway, by lectins such as mannose-binding protein that bind to sugars, or through the continuous low-grade turnover of the AP. The deposited C3b serves as a nidus for amplification of C3b deposition via the positive feedback loop. Control of this amplification process is critical to prevent undesirable injury to host cells. The presence of antibodies or lectins on a membrane at a site relatively lacking in membrane regulators is conducive to excessive complement activation on self tissue.