Hereditary angioedema: Looking for bradykinin production and triggers of vascular permeability. Issue 11 (21st October 2019)

• Record Type: Journal Article
• Authors: Margaglione, Maurizio; D'Apolito, Maria; Santocroce, Rosa; Maffione, Angela Bruna
• Is Part Of: Clinical & experimental allergy. Volume 49:Issue 11(2019)
• Page Start: 1395
• Page End: 1402
• Publication Date: 2019-10-21
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.13506
• Languages: English
• ISSNs: 0954-7894

Abstract

Abstract: Since the Osler's identification of the inherited nature of hereditary angioedema, a huge array of information was collected on pathogenetic mechanisms of the disease. Over the last years, information grew fast, and mutations in different genes, in addition to C1‐inhibitor, were found to be causative. All types are inherited as autosomal‐dominant traits with incomplete penetrance and little or no genotype‐phenotype correlation. As a result, the clinical expression is characterized by a large heterogeneity. The acknowledgement of mechanisms leading to heterogeneity of the clinical phenotype is likely to provide important information not only for a better understanding of the pathogenesis but also for therapy. Regardless of which gene is mutated, similar pathways seem to play a pivotal role, triggering the up‐regulation of contact activation system/kallikrein kinin system and giving rise to an unbalanced increase of bradykinin. However, notwithstanding the increase of bradykinin in bloodstream, the phenomenon is localized and no general vascular leakage and oedema is recognized. Thus, it is conceivable that there exist one or more localized factors that stimulate the production of bradykinin, which does not become a systemically event. Uncovering of these factors may shed lights on the missing part of the pathogenesis of hereditary angioedema. The present review, collecting information on pathogenesis from biochemical and genetics investigations, tries to provide a comprehensive view of the pathogenesis of hereditary angioedema. This can allow for a better understanding of the disease and lead to focused investigations that can further improve our knowledge.