Autoimmune angioedema: a new role for autoantibody in disease pathogenesis.
Angioedema may be due to hereditary forms of Cl-Inh 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 Cl-Inh in normal quantities, the Cl-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 Cl-Inh molecule. The following sequence of events is proposed: structural and functionally normal Cl-Inh is synthesised and secreted, this secreted inhibitor is complexed by autoantibody and following enzyme interaction, denatured 96 KD Cl-Inh is proposed. This process depletes the pool of normal, functional Cl-Inh to critical levels and predisposes patients to episodes of oedema.
Jackson
J
J
Department of Immunology, St. James's Hospital, Dublin, Ireland.
Feighery
C
C
D000799:Angioedema / Q000097:blood / Q000276:immunology* / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000628:therapy; D003174:Complement C1 Inactivator Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000187:drug effects / Q000276:immunology*; D010450:Endopeptidases / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008970:Molecular Weight; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation
D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D010450:Endopeptidases