The Role of Bradykinin Receptors in Hereditary Angioedema Due to C1-Inhibitor Deficiency

Abstract

Background: Hereditary angioedema (HAE) is a rare, genetic disease caused by the decreased level or function of the C1 inhibitor. The primary mediator of symptoms in HAE is bradykinin acting through its two receptors, namely receptors 1 (BR1) and 2 (BR2). Although BR2 is well characterized, the role of BR1 remains unclear. Objective: To study the role of bradykinin receptors 1 (BR1) in the etiopathogenesis of HAE. Methods: A total of 70 individuals, 40 patients with HAE, and 30 healthy subjects were recruited to the study. HAE was diagnosed in accordance with the international guideline. The level of bradykinin receptors was determined in populations of CD3+, CD4+, CD8+, and CD14++CD16−, CD14++CD16+ monocytes. In addition, the level of disease activity-specific markers was measured. Results: There were statistically significant differences in the subpopulation of lymphocytes and monocytes between patients with HAE compared to healthy subjects. The level of BR1 and BR2 on PBMCs was comparable in healthy subjects and HAE patients during remission with significant overexpression of both receptors, triggered by HAE attack. Moreover, a significant increase in TNF-alpha and IL-1 plasma levels was observed among HAE patients. Conclusions: BR1 expression may play an important role in the pathomechanism of HAE.

Patient-rated angioedema severity using a novel photo-aid for predicting non-mast cell mediator-induced angioedema diagnosis

“… 21 The increased binding of bradykinin and bradykinin-2 receptors and the relatively increased bradykinin-1 receptor expression might also cause AE to be more common in some locations. 22 , 23 Taken together, the difference among mediators in their vasoactive potency, sensitivity, and distribution of their receptors, and the characteristics of endothelial tight junctions in different organs may account for AE occurring in different body sites. 24 …”