Autoimmune Angioedema: a New Role for Autoantibody in Disease Pathogenesis

Abstract

Angioedema may be due to hereditary forms of CI-lnh deficiency, but recently an autoimmune form of angioedema has been described in which the mechanism is novel. While the peripheral blood monocytes of patients with autoimmune angioedema produce a normal, functionally active, 105 KD CI-Inh in normal quantities, the CI-Inh isolated from the patient's plasma exists in a dysfunctional lower molecular weight (96 KD) performance. Rather than bind and biologically inactivate the enzyme, a relatively common phenomenon in autoimmune disease, the autoimmune angioedema cleave the CI-Inh molecule. The following sequence of events is proposed: structural and functionally normal CI-lnh is synthesised and secreted, this secreted inhibitor is complexed by autoantibody and following enzyme interaction. denatured 96 KD CI-lnh is proposed. This process depletes the pool of normal, functional CI-lnh to crticial levels and predisposes patients to episodes of oedema.