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The effects of high dose interferon-β1a on plasma microparticles: correlation with MRI parameters
Mary Lowery-Nordberg1, Erin Eaton, Eduardo Gonzalez-Toledo
1Department of Pathology LSU Health Sciences Center-Shreveport, Shreveport, LA 71130-3932, USA.
Objectives:
We previously reported a correlation between levels of micro particles carrying CD31 (PMP(CD31+)) and disease activity in MS. However, the effects of long term (12 month) treatment with high dose, high frequency interferon-β1a (Rebif™) on plasma levels of PMP(CD31+), PMP(CD146+), and PMP(CD54+) and MRI measures of disease activity have not yet been assessed.
Methods:
During this prospective 1-year study, we used flow cytometry to measure changes in plasma micro particles (PMP) bearing CD31 (PMP(CD31+)), CD146 (PMP(CD146+)), and CD54/ICAM-1 (PMP(CD54+)) in 16 consecutive patients with relapsing-remitting MS (RRMS) before and after 3, 6, and 12 months of subcutaneous therapy with interferon-beta1a (44 micrograms, 3X weekly). At each visit, clinical exams and expanded disability status scale (EDSS) scores were recorded.
Results:
Plasma levels of PMP(CD31+), and PMP(CD54+) were significantly reduced by treatment with IFN-β1a. PMP(CD146+) appeared to decrease only at 3 months and did not persist at 6 and 12 months (p = 0.0511). In addition, the decrease in plasma levels of PMP(CD31+) and PMP(CD54+) levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions.
Conclusion:
Our data suggest that serial measurement of plasma micro particles (PMP), particularly in the initial stages of MS (when neuro-inflammatory cascades are more intense), may serve as reliable and reproducible surrogate markers of response to IFN-β1a therapy for MS. In addition, the progressive decline in plasma levels of PMP(CD31+) and PMP(CD54+) further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.
Insights
Treatment with interferon-beta1a significantly reduced plasma levels of specific micro particles (PMP(CD31+) and PMP(CD54+)) in MS patients. These reductions correlated with decreased MRI-detected disease activity, suggesting PMP as a potential marker for treatment response.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
Background:
- Previous studies indicated a correlation between CD31-carrying micro particles (PMP(CD31+)) and multiple sclerosis (MS) disease activity.
- The long-term impact of interferon-beta1a (IFN-β1a) on various plasma micro particle levels and MRI measures in MS remained unassessed.
Purpose of the Study:
- To evaluate the effect of 12-month high-dose, high-frequency IFN-β1a treatment on plasma levels of PMP(CD31+), PMP(CD146+), and PMP(CD54+) in relapsing-remitting MS (RRMS) patients.
- To assess the relationship between changes in these micro particle levels and MRI-defined disease activity.
Main Methods:
- Prospective 1-year study involving 16 RRMS patients receiving subcutaneous IFN-β1a (44 mcg, 3X weekly).
- Flow cytometry was used to measure plasma micro particle (PMP) levels (PMP(CD31+), PMP(CD146+), PMP(CD54+)) at baseline and after 3, 6, and 12 months.
- Clinical examinations, EDSS scores, and MRI scans were performed at each visit.
Main Results:
- IFN-β1a treatment led to significant reductions in plasma PMP(CD31+) and PMP(CD54+) levels.
- PMP(CD146+) levels showed a transient decrease at 3 months, but this was not sustained.
- The decrease in PMP(CD31+) and PMP(CD54+) at 12 months was associated with a significant reduction in contrast-enhancing T1 lesions on MRI.
Conclusions:
- Serial measurement of plasma micro particles, especially PMP(CD31+) and PMP(CD54+), may serve as reliable surrogate markers for monitoring IFN-β1a treatment response in MS.
- The observed decline in PMP levels supports the role of IFN-β1a in stabilizing cerebral endothelial cells during MS pathogenesis.
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