Phenotypical and Functional Characterization of Neutrophils in Two Pyrin-Associated Auto-inflammatory Diseases.
Adult
Aged
Calgranulin A
/ blood
Calgranulin B
/ blood
Cytokines
/ blood
Familial Mediterranean Fever
/ blood
Female
Humans
Inflammation
/ blood
Male
Matrix Metalloproteinase 9
/ blood
Middle Aged
Neutrophils
/ immunology
Peroxidase
/ immunology
Phagocytosis
Phenotype
Pyrin
/ genetics
Skin Diseases
/ blood
Transcriptome
Young Adult
Autoinflammation
FMF
PAAND
innate immunity
neutrophils
pyrin
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
05
02
2021
accepted:
23
02
2021
pubmed:
6
3
2021
medline:
4
2
2022
entrez:
5
3
2021
Statut:
ppublish
Résumé
Familial Mediterranean Fever (FMF) and Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) are clinically distinct autoinflammatory disorders caused by mutations in the pyrin-encoding gene MEFV. We investigated the transcriptional, phenotypical, and functional characteristics of patient neutrophils to explore their potential role in FMF and PAAND pathophysiology. RNA sequencing was performed to discover transcriptional aberrancies. The phenotypical features, degranulation properties, and phagocytic capacity of neutrophils were assessed by flow cytometry. Production of reactive oxygen species (ROS), myeloperoxidase (MPO) release, and chemotactic responses were investigated via chemiluminescence, ELISA, and Boyden chamber assays, respectively. Neutrophils from PAAND and FMF patients showed a partially overlapping, activated gene expression profile with increased expression of S100A8, S100A9, S100A12, IL-4R, CD48, F5, MMP9, and NFKB. Increased MMP9 and S100A8/A9 expression levels were accompanied by high plasma concentrations of the encoded proteins. Phenotypical analysis revealed that neutrophils from FMF patients exhibited an immature character with downregulation of chemoattractant receptors CXCR2, C5aR, and BLTR1 and increased expression of Toll-like receptor 4 (TLR4) and TLR9. PAAND neutrophils displayed an increased random, but reduced CXCL8-induced migration. A tendency for enhanced random migration was observed for FMF neutrophils. PAAND neutrophils showed a moderately but significantly enhanced phagocytic activity as opposed to neutrophils from FMF patients. Neutrophils from both patient groups showed increased MPO release and ROS production. Neutrophils from patients with FMF and PAAND, carrying different mutations in the MEFV gene, share a pro-inflammatory phenotype yet demonstrate diverse features, underscoring the distinction between both diseases.
Identifiants
pubmed: 33666778
doi: 10.1007/s10875-021-01008-4
pii: 10.1007/s10875-021-01008-4
doi:
Substances chimiques
Calgranulin A
0
Calgranulin B
0
Cytokines
0
MEFV protein, human
0
Pyrin
0
S100A8 protein, human
0
S100A9 protein, human
0
Peroxidase
EC 1.11.1.7
MMP9 protein, human
EC 3.4.24.35
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1072-1084Références
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