Increased concentrations of P2X7R in oligodendrocyte derived extracellular vesicles of Multiple sclerosis patients.
Neurobiol Dis
; 199: 106601, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38996986
ABSTRACT
Activation of the purinergic receptor P2X7 (P2X7R) is believed to be deleterious in autoimmune diseases and it was hypothesized to play a role in the pathogenesis of MS. P2X7R is an ATP-gated non-selective cationic channel; its activation can be driven by high concentrations of ATP and leads to the generation of large, cytolytic conductance pores. P2X7R activation can also result in apoptosis as a consequence of the activation of the caspase cascade via P2X7R-dependent stimulation of the NLRP3 inflammasome. We measured P2X7R in oligodendrocyte derived extracellular vesicles (ODEVs) in MS patients and in healthy subjects. Sixty-eight MS patients (50 relapsing-remitting, RR-MS, 18 primary progressive, PP-MS) and 57 healthy controls (HC) were enrolled. ODEVs were enriched from serum by a double step immunoaffinity method using an anti OMGp (oligodendrocyte myelin glycoprotein) antibody. P2X7R concentration was measured in ODEVs lysates by ELISA. One-way Anova test showed that P2X7R in ODEVs is significantly higher in PP-MS (mean 1742.89 pg/mL) compared both to RR-MS (mean 1277.33 pg/mL) (p < 0.001) and HC (mean 879.79 pg/mL) (p < 0.001). Comparison between RR-MS and HC was also statistically significant (p < 0.001). Pearson's correlations showed that P2RX7 in ODEVs was positively correlated with EDSS (p = 0.002, r = 0.38, 0.15-0.57 95% CI) and MSSS (p = 0.004, r = 0.34, 0.12-0.54 95% CI) scores, considering MS patients together (PP-MS + RR-MS) and with disease duration in PP-MS group (p = 0.02, r = 0.53, 0.09-0.80 95% CI). Results suggest that ODEVs-associated P2X7R levels could be a biomarker for MS.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodendroglia
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Receptores Purinérgicos P2X7
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Vesículas Extracelulares
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália