Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities

Abstract

SUMMARYThe mediator(s) responsible for localized enhanced vascular permeability that characterizes an exacerbation of hereditary angioneurotic oedema (HAE) is thought to be a product of either contact or complement system activation. In contrast to normal individuals, plasma from these patients generates both kinin and vascular permeability-enhancing activity following incubation at 37°C. Depletion of C1 inhibitor in both normal and C2-deficient plasma, but not in contact factor-deficient plasmas, resulted in generation ofthese activities. The kinin activity from incubated HAE plasma was susceptible to kininase inactivation and was blocked by a Bk2 receptor antagonist. Furthermore, this activity was isolated from HAE plasma; amino acid sequence analysis proved it to be bradykinin. Similarly, the vasopermeability-enhancing activity from ethanol-fractionated or boiled HAE plasma, collected during either attack or remission, co-eluted with bradykinin on reverse-phase high performance liquid chromatography (HPLC). These studies conclusively demonstrate that bradykinin is the major kinin and mediator ofenhanced vascular permeability generated during incubation of HAE plasma. The role of other bioactive products, such as the C2 kinin, at local sites of oedema formation remains to be further defined.

Pathophysiology of Hereditary Angioedema

“…It was originally proposed that complement activation may play a principle role in the pathogenesis of these symptoms, but this was later discredited. [23][24][25][26][27] It is known that minor local trauma, stress, and other events may trigger angioedema, and it is now well established that bradykinin (BK) is the principal mediator of symptoms of C1-INH deficiency.…”

Hereditary and Acquired Complement Component 1 Esterase Inhibitor Deficiency: A Review for the Hematologist

“…Most importantly, increased bradykinin production has been demonstrated in patients with type I and type II HAE. Shoemaker et al [37] compared kinin activity in plasma samples from HAE patients and normal controls. The HAE samples demonstrated kinin activity that, upon amino acid sequencing, proved to be bradykinin.…”

Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies

“…Increased bradykinin levels increase vascular permeability and extravasation, manifesting as edema (Figure 2)[1,28-30]. This is an important differentiating feature of HAE when compared with allergic reactions, which are primarily mediated by histamine.…”