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Blood circulating microparticle species in relapsing-remitting and secondary progressive multiple sclerosis. A
J S Alexander1, R Chervenak2, B Weinstock-Guttman3
1Department of Molecular and Cellular Physiology, Louisiana State University Health-Shreveport, LA, USA.
Background:
Although multiple sclerosis (MS) is thought to represent an excessive and inappropriate immune response to several central nervous system (CNS) autoantigens, increasing evidence also suggests that MS may also be a neurovascular inflammatory disease, characterized by endothelial activation and shedding of cell membrane microdomains known as 'microparticles' into the circulation.
Objective:
To investigate the relationships between these endothelial biomarkers and MS.
Methods:
We examined the relative abundance of CD31(+)/PECAM-1, CD51(+)CD61(+) (αV-β3) and CD54(+) (ICAM-1) bearing microparticles in sera of healthy individuals, patients with relapsing-remitting MS, and secondary-progressive MS. We also investigated the correlation among circulating levels of different microparticle species in MS with conventional MRI (T2- and T1-lesion volumes and brain atrophy), as well as novel MR modalities [assessment of iron content on susceptibility-weighted imaging (SWI)-filtered phase].
Results:
Differences in circulating microparticle levels were found among MS groups, and several microparticle species (CD31(+)/CD51(+)/CD61(+)/CD54(+)) were found to correlate with conventional MRI and SWI features of MS.
Conclusion:
These results indicate that circulating microparticles' profiles in MS may support mechanistic roles for microvascular stress and injury which is an underlying contributor not only to MS initiation and progression, but also to pro-inflammatory responses.
Insights
Circulating microparticles, indicators of endothelial stress, are linked to multiple sclerosis (MS) progression and inflammation. These biomarkers correlate with MRI findings, suggesting a role in MS pathogenesis.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Biomarker Discovery
Background:
- Multiple sclerosis (MS) is traditionally viewed as an autoimmune CNS disease.
- Emerging evidence suggests MS also involves neurovascular inflammation and endothelial activation.
- Endothelial cell microparticles are released into circulation during activation.
Purpose of the Study:
- To investigate the relationship between endothelial microparticles and MS.
- To correlate microparticle levels with MS disease activity and brain changes.
Main Methods:
- Quantified CD31, CD51/CD61 (αV-β3), and CD54 microparticles in serum from healthy controls and MS patients (relapsing-remitting and secondary-progressive).
- Assessed correlations between microparticle levels and conventional MRI (lesion volume, atrophy) and advanced MRI (SWI-filtered phase for iron content).
Main Results:
- Distinct circulating microparticle profiles were observed in different MS groups.
- Specific microparticle species (CD31, CD51, CD61, CD54) correlated with conventional MRI and SWI features of MS.
- These findings suggest microparticles reflect disease activity.
Conclusions:
- Circulating microparticle profiles in MS support a role for microvascular stress and injury.
- Microvascular factors may contribute to MS initiation, progression, and inflammation.
- Endothelial biomarkers offer insights into MS pathophysiology.
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