PhD Scientific Days 2024

Budapest, 9-10 July 2024

Theoretical and Translational Medicine II.

Mast Cell Mediators in Hereditary Angioedema


Hanga Réka Horváth1, Noémi Andrási2,3, Eszter Nagy4,5, Éva Imreh4, Henriette Farkas2
1: Hungarian Angioedema Center of Reference and Excellence, Department of Internal Medicine and Haematology, Semmelweis University
2: Hungarian Angioedema Center of Reference and Excellence, Department of Haematology and Internal Medicine, Semmelweis University, Budapest, Hungary
3: Pediatric Center, Tűzoltó Street Department, Semmelweis University, Budapest, Hungary
4: Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary
5: Central Laboratory, National Institute of Musculoskeletal Diseases, Budapest

Text of the abstract

Introduction: In hereditary angioedema with C1 inhibitor deficiency (HAE-C1INH), the decreased activity of C1 inhibitor can cause activation of the complement system producing C3a and C5a, which can activate mast cells. During the degranulation of mast cells, heparin is released, which can activate the contact kinin-kallikrein system via factor XII, leading to increased bradykinin production. These processes raise the possibility of a link between HAE-C1INH and allergic diseases. In our previous epidemiological survey, we found a nearly three times higher incidence of hypersensitivity reactions among our HAE-C1INH patients compared to the adult Hungarian population.
Aims: The aim of our present study was to investigate molecular correlations between HAE-C1INH and allergic diseases.
Methods: Blood samples were taken from patients during angioedema attack (HAE-A) and during symptom-free period (HAE-SF), as well as from healthy controls. We selected patients and control subjects with no history of allergic disease and with normal levels of both nutritional and inhalant specific IgE levels. Tryptase, chymase, platelet-activating factor, leukotriene B4, diamine oxidase (DAO) and eosinophil cationic protein (ECP) were measured.
Results: The serum level of chymase was higher in both HAE-C1INH groups than in the control group (p=0.020 in both comparisons), while comparing the HAE-A and HAE-SF groups, no difference was found. On the other hand, DAO and ECP did not differ from the control group, but in HAE-C1INH patients we measured increased levels during angioedema attack compared to the asymptomatic state (p=0.018 and 0.004, respectively). No difference was found in the levels of the other three mediators in any comparison.
Conclusion: Of the four investigated mediators released from mast cells, chymase showed a significant difference between HAE-C1INH patients and the control group, raising the possibility of the activation of a specific subset of mast cells in HAE-C1INH patients. On the other hand, the level of ECP, which indicates eosinophil activation, and the histamine-degrading enzyme DAO slightly increased in angioedema attack, which suggests that other processes outside of the kinin-kallikrein system may also play a role in angioedema attack formation.
Funding: The research was carried out with the support of MAKIT's 2023 Topic Competition.