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Increased concentrations of P2X7R in oligodendrocyte derived extracellular vesicles of Multiple sclerosis patients
Cristina Agliardi1, Franca Rosa Guerini1, Milena Zanzottera1
1IRCCS Fondazione Don Carlo Gnocchi ONLUS, Via Capecelatro 66, Milan, Italy.
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.
Insights
Levels of purinergic receptor P2X7 (P2X7R) in oligodendrocyte derived extracellular vesicles (ODEVs) were significantly elevated in multiple sclerosis (MS) patients compared to healthy subjects. These ODEV-associated P2X7R levels correlate with disease severity, suggesting potential as a biomarker for MS.
Area of Science:
- Neuroimmunology
- Cell Biology
- Biochemistry
Background:
- The purinergic receptor P2X7 (P2X7R) is implicated in autoimmune diseases, potentially contributing to multiple sclerosis (MS) pathogenesis.
- P2X7R activation, triggered by high ATP concentrations, forms cytolytic pores and can induce apoptosis via caspase cascade and NLRP3 inflammasome activation.
Purpose of the Study:
- To investigate the concentration of P2X7R within oligodendrocyte derived extracellular vesicles (ODEVs) in MS patients and healthy controls.
- To determine if ODEV-associated P2X7R levels correlate with MS disease severity and progression.
Main Methods:
- Serum samples from 68 MS patients (50 RR-MS, 18 PP-MS) and 57 healthy controls (HC) were analyzed.
- ODEVs were isolated using immunoaffinity enrichment targeting oligodendrocyte myelin glycoprotein (OMGp).
- P2X7R concentration in ODEV lysates was quantified using ELISA, and correlations with clinical scores (EDSS, MSSS) and disease duration were assessed.
Main Results:
- P2X7R levels in ODEVs were significantly higher in primary progressive MS (PP-MS) patients compared to relapsing-remitting MS (RR-MS) patients and HC (p < 0.001).
- ODEV-associated P2X7R levels were also significantly higher in RR-MS patients compared to HC (p < 0.001).
- P2X7R concentration in ODEVs positively correlated with Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) in all MS patients, and with disease duration in PP-MS patients.
Conclusions:
- ODEV-associated P2X7R levels are significantly elevated in MS patients, particularly in the progressive form.
- These findings suggest that ODEV-associated P2X7R may serve as a potential biomarker for MS diagnosis and severity assessment.
