Immune complex-mediated neutrophil activation in patients with polymyalgia rheumatica.
PMR
calprotectin
immune complexes
neutrophil extracellular traps
neutrophils
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
received:
29
09
2022
accepted:
21
12
2022
medline:
3
8
2023
pubmed:
24
12
2022
entrez:
23
12
2022
Statut:
ppublish
Résumé
Neutrophils are important in host defence. However, neutrophils are also linked to inflammation and organ damage. The purpose of this study was to assess whether markers of neutrophil activation are increased in PMR. Levels of immune complexes (IC), calprotectin and neutrophil extracellular traps (NETs) were measured in plasma of healthy individuals (n = 30) and patients with PMR (n = 60), at flare and upon treatment with glucocorticoids using ELISA. Plasma-mediated neutrophil activation was assessed in presence of an FcγRIIA inhibitory antibody (IV.3). Plasma levels of calprotectin and NETs were elevated in PMR (P < 0.001). Mechanistically, neutrophil activation was driven by ICs, present in plasma, able to up-regulate neutrophil activation markers CD66b and CD11b (P < 0.0001) in an FcγRIIA-dependent manner (P < 0.01). Of note, circulating levels of IC correlated with plasma induced CD66b and CD11b (r = 0.51, P = 0.004, and r = 0.46, P = 0.01, respectively) and decreased after glucocorticoid therapy. In contrast to NETs, calprotectin significantly decreased after glucocorticoid therapy (P < 0.001) and was higher in PMR without overlapping GCA compared with patients with overlapping disease (P = 0.014). Interestingly, musculoskeletal involvement was associated with elevated levels of calprotectin before initiation of glucocorticoid therapy (P = 0.036). Neutrophil activation, including NET formation, is increased in PMR, through IC-mediated engagement of FcγRIIA. Clinically, neutrophil activation is associated with musculoskeletal involvement, with calprotectin, but not NETs, being a biomarker of treatment response in PMR patients. In all, IC-mediated neutrophil activation is a central process in PMR pathogenesis identifying potential novel therapeutic targets (FcγRIIA), as well as soluble markers for disease monitoring (calprotectin).
Identifiants
pubmed: 36562570
pii: 6958551
doi: 10.1093/rheumatology/keac722
pmc: PMC10393430
doi:
Substances chimiques
Antigen-Antibody Complex
0
Glucocorticoids
0
Leukocyte L1 Antigen Complex
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2880-2886Subventions
Organisme : NEI NIH HHS
ID : R21 EY029391
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR057512
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007028
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.
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