A new study has investigated whether the excess neutrophil granulocyte (NG) count typical in patients with hereditary angioedema (HAE) is due to a maturation disorder, biased circulating vs marginated pool equilibrium, or reduced elimination.

The study, published in Scientific Reports, observed normal maturation of NGs but decreased adhesion to the endothelial cells (ECs) compared with healthy controls.

“Myeloperoxidase and neutrophil elastase measurements showed that NGs in C1-inhibitor (C1-INH) deficiency [C1-INH-HAE] patients in a symptom-free state were more activated than those in healthy controls,” the authors wrote. “We aimed to investigate the presence of NG progenitors, the expression of adhesion molecules and cytokine receptors, the production of NG effector molecules/systems…and the comparison of adhesive characteristics to endothelial cells in C1-INH-HAE patients and healthy controls.”

Explore more great content on Hereditary Angioedema (HAE) →
The Pathophysiology and Clinical Manifestations of Hereditary Angioedema
The Challenges of Diagnosing and Managing Hereditary Angioedema
Hereditary Angioedema Often Impacts Patients’ Reproductive Decisions
Continue Reading

The research team enrolled 20 attack-free patients with C1-INH-HAE and 21 healthy controls and obtained blood samples from each. They employed flow cytometry to compare cell surface maturation, adhesion molecules, cytokine receptors and Ca2+ mobilization. They also compared activation markers using ELISA and NG adhesion to ECs with an automated pipetting system.

Read more about HAE etiology

The results revealed that ECs that were pretreated with lipopolysaccharide or phorbol 12-myristate 13-acetate were significantly less adhered to NGs in patients compared with healthy controls, and this adhesion was unaffected by bradykinin.

In terms of soluble activation markers in the absence of stimuli, the NGs from patients with C1-INH-HAE were found to be in a more activated state than those of controls.

The authors concluded that bradykinin may not be responsible for the lack of adhesion of NGs to ECs and that there was a bias toward circulating NGs compared with marginated NGs in patients. The consequences of the mild NG activation observed in patients are not yet known and merit further research.

Reference

Kajdácsi E, Balla Z, Pólai Z, Cervenak L, Farkas H. Decreased adhesion to endothelium leads to elevated neutrophil granulocyte count in hereditary angioedema patients. Sci Rep. Published online August 17, 2023. doi.10.1038/s41598-023-40442-9

dermatologists Gastroenterologists immunologists Researchers