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Myelin Basic Protein in Oligodendrocyte-Derived Extracellular Vesicles as a Diagnostic and Prognostic Biomarker in
Cristina Agliardi1, Franca Rosa Guerini1, Milena Zanzottera1
1IRCCS Fondazione Don Carlo Gnocchi, 20147 Milan, Italy.
Abstract:
Approximately 15% of multiple sclerosis (MS) patients develop a progressive form of disease from onset; this condition (primary progressive-PP) MS is difficult to diagnose and treat, and is associated with a poor prognosis. Extracellular vesicles (EVs) of brain origin isolated from blood and their protein cargoes could function as a biomarker of pathological conditions. We verified whether MBP and MOG content in oligodendrocytes-derived EVs (ODEVs) could be biomarkers of MS and could help in the differential diagnosis of clinical MS phenotypes. A total of 136 individuals (7 clinically isolated syndrome (CIS), 18 PPMS, 49 relapsing remitting (RRMS)) and 70 matched healthy controls (HC) were enrolled. ODEVs were enriched from serum by immune-capture with anti-MOG antibody; MBP and MOG protein cargoes were measured by ELISA. MBP concentration in ODEVs was significantly increased in CIS (p < 0.001), RRMS (p < 0.001) and PPMS (p < 0.001) compared to HC and was correlated with disease severity measured by EDSS and MSSS. Notably, MBP concentration in ODEVs was also significantly augmented in PPMS compared to RRMS (p = 0.004) and CIS (p = 0.03). Logistic regression and ROC analyses confirmed these results. A minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis.
Insights
A blood test measuring myelin basic protein (MBP) in brain-derived extracellular vesicles (EVs) shows promise for diagnosing multiple sclerosis (MS). Elevated MBP levels in EVs can help differentiate between primary progressive MS and other MS subtypes.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Neurodegenerative Diseases
Background:
- Multiple sclerosis (MS) presents diagnostic and prognostic challenges, particularly the primary progressive (PPMS) form.
- Extracellular vesicles (EVs) from the brain, found in blood, offer potential as biomarkers for neurological conditions.
- Oligodendrocyte-derived EVs (ODEVs) carry specific protein cargoes relevant to MS pathology.
Purpose of the Study:
- To investigate myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) in O পার্থক্যDEVs as potential biomarkers for MS diagnosis.
- To assess the utility of ODEV protein content in differentiating between clinical MS phenotypes (CIS, RRMS, PPMS).
Main Methods:
- Serum ODEV isolation using anti-MOG antibody immune-capture.
- Quantification of MBP and MOG protein cargoes within ODEVs via ELISA.
- Analysis of 136 individuals (7 CIS, 18 PPMS, 49 RRMS) and 70 healthy controls (HC).
Main Results:
- MBP concentration in ODEVs was significantly elevated across all MS subtypes (CIS, RRMS, PPMS) compared to HC.
- MBP levels in ODEVs correlated with MS disease severity (EDSS, MSSS).
- Significantly higher MBP concentrations were observed in PPMS compared to RRMS and CIS, confirmed by logistic regression and ROC analysis.
Conclusions:
- Concentration of MBP in ODEVs is a potential diagnostic biomarker for MS.
- Measuring MBP in ODEVs could aid in the differential diagnosis of MS clinical phenotypes.
- A minimally invasive blood test for ODEV-MBP offers a promising tool for facilitating MS diagnosis.
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