Increased concentrations of P2X7R in oligodendrocyte derived extracellular vesicles of Multiple sclerosis patients.
Neurobiol Dis
; : 106601, 2024 Jul 10.
Article
in 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 1742.89â¯pg/mL) compared both to RR-MS (mean 1277.33â¯pg/ml) (pâ¯<â¯0.001) and HC (mean 879.79â¯pg/mL) (pâ¯<â¯0.001). Comparison between RR-MS and HC was also statistically significant (pâ¯<â¯0.001). Pearson's correlations showed that P2RX7 in ODEVs was positively correlated with EDSS (pâ¯=â¯0.002, râ¯=â¯0.38, 0.15-0.57 95% CI) and MSSS (pâ¯=â¯0.004, râ¯=â¯0.34, 0.12-0.54 95% CI) scores, considering MS patients together (PP-MSâ¯+â¯RR-MS) and with disease duration in PP-MS group (pâ¯=â¯0.02, râ¯=â¯0.53, 0.09-0.80 95% CI). Results suggest that ODEVs-associated P2X7R levels could be a biomarker for MS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Italia