PATHOGENETIC AND CLINICAL ASPECTS OF C1 INHIBITOR DEFICIENCY

Citation
M. Cicardi et al., PATHOGENETIC AND CLINICAL ASPECTS OF C1 INHIBITOR DEFICIENCY, Immunobiology, 199(2), 1998, pp. 366-376
Citations number
34
Categorie Soggetti
Immunology
Journal title
ISSN journal
01712985
Volume
199
Issue
2
Year of publication
1998
Pages
366 - 376
Database
ISI
SICI code
0171-2985(1998)199:2<366:PACAOC>2.0.ZU;2-I
Abstract
People deficient in C1-INH present recurrent angioedema localized to s ubcutaneous or mucous tissues. The defect can be caused by impaired sy nthesis, due to a genetic defect (hereditary angioedema), or by increa sed catabolism (acquired angioedema). In our experience the majority o f patients with acquired angioedema (16 of 18) have autoantibodies to C1-INH in their serum. These autoantibodies bind to C1-INH with differ ent and generally low affinity. The vasopermeability mediator responsi ble for attacks is still undefined: bradykinin (derived from cleavage of high molecular weight kininogen) and a kinin-like peptide (derived from the second component of complement) still remain the two primary candidates. We examined the systems controlled by C1-INH (complement, contact system, fibrinolysis and coagulation) and found that all of th em are activated during angioedema attacks. Activation of the coagulat ion leads to generation of thrombin whose vasoactive effect can thus i nfluence edema formation. Treatment of severe angioedema attacks is sa tisfactorily performed with C1-INH plasma concentrate although patient s with an acquired defect frequently need very high doses. Attenuated androgens effectively prevent attacks in hereditary angioedema, but th eir safety, on the very long-term, needs to be further assessed. Acqui red angioedema generally fail to respond to these drugs, but can be tr eated prophylactically with antifibrinolytic agents.