Characterising Endovascular Profiles in ACE Inhibitor-Induced Angioedema in a South African Cohort - European Medical Journal

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Characterising Endovascular Profiles in ACE Inhibitor-Induced Angioedema in a South African Cohort

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Allergy & Immunology
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Authors:
* Sarah Pedretti , 1,2 Rachael Gachogo , 2 Nomawethu Masina , 1 Cascia Day , 2 Jonny Peter 1,2
  • 1. Allergy and Immunology Unit, University of Cape Town Lung Institute, South Africa
  • 2. Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, South Africa
*Correspondence to [email protected]
Disclosure:

Pedretti has received travel support for attendance at the EAACI Congress from the University of Cape Town. Day has received honoraria from the Allergy Foundation of South Africa; and holds a leadership role in the Allergy Society of South Africa Executive Committee, Education Division. Peter has received grants from NIHR Global Professorship, the South African Medical Research Council, the Wellcome Trust, and the National Institutes of Health; has participated on advisory boards for Argo Biopharma, Novartis, and ITM Belgium; and holds leadership roles in the Allergy of South Africa Executive Committee, National Immunisation Safety Executive Committee, IUIS Clinical Immunology Committee, WAO Drug Allergy Committee, and AAAAI Drug and Latex Committee. The other authors have declared no conflicts of interest. The present manuscript received research funding from the South African Medical Research Council.

Acknowledgements:

The authors would like to thank the patients, without whom this work would not be possible. They also thank Wisahl Wallace, Thandokazi Bezana, and Nomafu Jayiya for all administrative assistance. Appreciation is extended by the authors to the Provincial Health Data Centre (PHDC) team for their valuable contributions. Situated within the Western Cape Government: Department of Health and Wellness, the Provincial Health Data Centre functions as a Health Information Exchange, established to positively impact patient care and health outcomes by leveraging data and technology.

Keywords:
Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI), bradykinin (BK), endothelial activation, inflammation, Olink® proteomics (Thermo Fisher Scientific, Waltham, Massachusetts, USA), vascular inflammation, vascular permeability.
Citation:
EMJ Allergy Immunol. ;11[1]:30-31. https://doi.org/10.33590/emjallergyimmunol/C0Z0005N.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

BACKGROUND AND AIMS

Angiotensin-converting enzyme inhibitor-induced angioedema (AE-ACEI) is more frequent in Black African populations.1,2 Although bradykinin (BK) is central to current models, incomplete response to B2 receptor antagonism3 suggests additional inflammatory and endothelial activation mechanisms during acute attacks. The authors’ aim was to characterise inflammatory and endothelial markers in AE-ACEI cases by measuring plasma and serum profiles during acute episodes and recovery, compared with ACEI-tolerant controls.4

MATERIALS AND METHODS

Over 4 years, 54 patients with AE-ACEI were sampled during acute episodes (AE) and at follow-up (FU; 3–6 months post-AE), alongside 91 ACEI-tolerant matched controls (MC; median [interquartile range]: 10.4 [7.9] years on ACEI). Plasma BK, secreted phospholipase 2 (sPLA2), and vascular endothelial growth factor (VEGF) were quantified by ELISA. Serum tryptase and total IgE were measured using UniCAP fluoroimmunoassay. C-reactive protein (CRP), D-dimer, and fibrinogen were processed at the local National Reference Laboratory. A total of 92 inflammation-related proteins were profiled using proximity extension assay (Olink®, Thermo Fisher Scientific, Waltham, Massachusetts, USA). Wilcoxon testing with correction for multiple comparisons was applied.

RESULTS

Plasma BK levels were significantly higher in AE-ACEI cases, at both AE and FU, compared to MC. During AE, VEGF and sPLA2 levels were increased relative to FU and MC for VEGF only. Total IgE (measured only AE) was higher in AE-ACEI cases compared to MC. Acute CRP, D-dimer, and fibrinogen levels were elevated relative to FU and MC. Proteomic analysis demonstrated a distinct acute endovascular signature. Pairwise comparison between AE and FU revealed increased EN-RAGE and OSM in AE samples, accompanied by vascular permeability and repair mediators (VEGFA, HGF), and endothelial–immune interaction markers (TNFSF14/LIGHT, CD40, TGF-α). Importantly, FU samples did not differ from MC after multiple-testing correction, indicating resolution of the acute proteomic signature.

CONCLUSION

AE-ACEI is characterised by a transient, attack-specific endovascular inflammatory programme involving RAGE-axis activation, endothelial permeability mediators, and immune–endothelial crosstalk, rather than isolated BK excess. The absence of proteomic differences at FU supports a reversible, event-locked vascular inflammatory process. Further work is required to understand distinct endotypes and compare with other acute angioedemas.

References
Brown NJ et al. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther. 1996;60(1):8-13. Burkhart DG et al. Angiotensin converting enzyme inhibitor-associated angioedema: higher risk in blacks than whites. Pharmacoepidemiol Drug Saf. 1996;5(3):149-54. Jeon J et al. Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: a meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2019;44(5):685-92. Pedretti S et al. Characterising endovascular profiles in ACE inhibitor–induced angioedema in a South African cohort. Abstract 100370. EAACI Congress, 12-15 June, 2026.

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