Endothelial cell activation during edematous attacks of hereditary angioedema types I and II

• Published in: Journal of allergy and clinical immunology 2014-06, Vol.133 (6), p.1686-1691
• Main Authors: Kajdácsi, Erika, MSc, Jani, Péter K., MSc, Csuka, Dorottya, PhD, Varga, Lilian Ágnes, PhD, Prohászka, Zoltán, MD, DSc, Farkas, Henriette, MD, DSc, Cervenak, László, PhD
• Format: Article
• Language: English
• Subjects: activation; Adult; Allergic diseases; Allergy and Immunology; Angioedema; Antigens; attack; Biological and medical sciences; Biomarkers - blood; Biomarkers - metabolism; C1-inhibitor deficiency; clinical study; endothelial cells; Endothelial Cells - immunology; Endothelial Cells - metabolism; endothelin-1; Endothelium; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hereditary angioedema; Hereditary Angioedema Types I and II - diagnosis; Hereditary Angioedema Types I and II - immunology; Hereditary Angioedema Types I and II - metabolism; Humans; Immunopathology; Male; Medical sciences; Patients; Permeability; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Smooth muscle; soluble E-selectin; von Willebrand factor
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.12.1072

Background Hereditary angioedema (HAE) caused by C1-inhibitor (C1-INH) deficiency (HAE–C1-INH) is a potentially life-threatening rare disease caused by the decreased activity of C1-INH. Lack of C1-INH leads to overproduction of bradykinin, a potent vasoactive peptide. Although angioedema is induced by bradykinin, the function and activation of endothelial cells (ECs), the targets of bradykinin, have not yet been studied during HAE attacks. Objective We studied whether EC function is altered during HAE attacks in comparison with attack-free intervals. Methods Forty-six consecutive samples obtained during attacks from 18 patients with HAE–C1-INH were compared with inter-attack samples of the same patients. The patients' sera were tested for von Willebrand factor (VWF) antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1 levels by using ELISA and BRAHMS Kryptor technologies. Results Levels of all 4 EC markers (VWF antigen, VWF collagen-binding activity, soluble E-selectin, and endothelin-1) were significantly increased during HAE attacks. Their increases were even more obvious in the subgroup of patients without any pre-existing risk factors for endothelial dysfunction. Conclusion In this study we demonstrated that ECs are activated during HAE attacks. Our results might suggest the need for revising the knowledge on the pathogenesis of HAE–C1-INH and for reconsidering the role of ECs as a possible novel therapeutic target in patients with this disease.