SEARCHCOHORTimmunology, hematology

cohort·immunology, hematology, internal medicine, preclinical research, biomedical research·PMC10435475

Decreased adhesion to endothelium leads to elevated neutrophil granulocyte count in hereditary angioedema patients

Scientific Reports · 5 authors, 2 centres

AI SUMMARY

FIDELITY 100%

POPULATIONAttack-free C1-inhibitor–deficient hereditary angioedema (C1-INH-HAE) patients

INTERVENTIONNone (observational in vitro study of patient-derived neutrophils)

COMPARISONHealthy controls

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

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TL;DR

In a cross-sectional study of 20 attack-free C1-INH-HAE patients and 21 healthy controls, neutrophils from patients showed reduced adhesion to activated endothelial cells and elevated baseline activation markers, while maturation was normal. These findings suggest the elevated neutrophil counts seen in HAE patients may result from a biased ratio between circulating and marginated pools due to decreased adhesion to endothelium.

Full summary

1,063 CHARS

This cohort study enrolled 20 attack-free C1-INH-HAE patients and 21 healthy controls to investigate the origin of elevated neutrophil granulocyte (NG) counts in C1-INH-HAE. Blood samples were analyzed by flow cytometry for maturation markers, adhesion molecules, and cytokine receptors; activation markers were measured by ELISA; and NG/endothelial cell adhesion was assessed using an automated pipetting system. Flow cytometry showed normal NG maturation in patients. Adhesion of NGs to endothelial cells pretreated with LPS or PMA was significantly weaker in patient samples compared to controls, and bradykinin had no effect on adhesion. NGs from patients showed elevated baseline activation markers without stimulation. The authors conclude that reduced adhesion properties bias the ratio between circulating and marginated NG pools, potentially explaining elevated counts. Limitations include small sample size due to the rarity of C1-INH-HAE, only investigation of neutrophils (not endothelial cells) in adhesion assays, and the retrospective study design.

PICO

PPOPULATION

Attack-free C1-inhibitor–deficient hereditary angioedema (C1-INH-HAE) patients

IINTERVENTION

None (observational in vitro study of patient-derived neutrophils)

OOUTCOME

Neutrophil adhesion to endothelial cells, activation markers, maturation markers, and adhesion molecule expression

STUDY TYPE

cohort

SPECIALTY

immunology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10435475

Decreased adhesion to endothelium leads to elevated neutrophil granulocyte count in hereditary angioedema patients

Scientific Reports

READ THE FULL PAPER

ABSTRACT

As many aspects of hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) cannot be explained with elevated bradykinin level alone, it has recently become clear that other factors also play an important role in the pathogenesis. One of these factors could be elevated neutrophil granulocyte (NG) counts, which are associated with increased NG activation in C1-INH-HAE patients; however, their origin has not been elucidated so far. Here, we aimed to investigate whether the excess of NGs is due to disturbed maturation, biased circulating/marginated pool equilibrium or decreased elimination. We enrolled 20 attack-free C1-INH-HAE patients together with 21 healthy controls and collected blood samples. We compared cell surface maturation markers, adhesion molecules, cytokine receptors, and Ca 2+ -mobilization of NG by flow cytometry, activation markers by ELISA, and NG/endothelial cell adhesion by automated pipetting system. Cell-surface markers showed normal maturation of NGs in C1-INH-HAE patients. Adhesion of NGs to endothelial cells pretreated with lipopolysaccharide or phorbol 12-myristate 13-acetate was significantly weaker in samples from C1-INH-HAE patients and bradykinin had no effect on the adhesion. NGs from C1-INH-HAE patients were in an activated state when assessed by soluble activation markers without any stimulation. Our data support that the maturation of NGs in C1-INH-HAE patients is normal, whereas adhesion properties of patient-derived NGs to the endothelium are reduced compared to those from healthy controls, indicating a bias between the circulating and marginated pools of NGs in patients. Bradykinin may not be responsible for reduced adhesion properties of NGs.

CITATION EXPORT

Erika Kajdácsi, Zsuzsanna Balla, Zsófia Pólai et al.. Decreased adhesion to endothelium leads to elevated neutrophil granulocyte count in hereditary angioedema patients. Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-40442-9

AUTHORS

5 · 2 CENTRES

Erika Kajdácsi, Zsuzsanna Balla, Zsófia Pólai, László Cervenak, Henriette Farkas

1https://ror.org/01g9ty582grid.11804.3c0000 0001 0942 9821Research Laboratory, Department of Internal Medicine and Haematology, Semmelweis University, Szentkirályi u. 46., Budapest, 1088 Hungary
2https://ror.org/01g9ty582grid.11804.3c0000 0001 0942 9821Hungarian Angioedema Center of Reference and Excellence, Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary