Abstract
ObjectivesWe previously reported a correlation between levels of microparticles 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 PMPCD31+, PMPCD146+, and PMPCD54+ and MRI measures of disease activity have not yet been assessed.MethodsDuring this prospective 1-year study, we used flow cytometry to measure changes in plasma microparticles (PMP) bearing CD31 (PMPCD31+), CD146 (PMPCD146+), and CD54/ICAM-1 (PMPCD54+) 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.ResultsPlasma levels of PMPCD31+, and PMPCD54+ were significantly reduced by treatment with IFN-β1a. PMPCD146+ 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 PMPCD31+ and PMPCD54+ levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions.ConclusionOur data suggest that serial measurement of plasma microparticles (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 PMPCD31+ and PMPCD54+ further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.
Highlights
Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the human central nervous system (CNS) characterized clinically by a relapsing-remitting course
MS manifests with development of demyelinating lesions which affect both gray and white matter [1,2] disruption of the blood brain barrier (BBB) and transendothelial migration of lymphocytes and macrophages across inflamed CNS endothelial monolayers appear to be among the earliest CNS and spinal
During this study we assessed the plasma microparticles (PMP) profiles in MS patients pre- and post treatment with IFN-b1a (Rebif) and found that several but not all classes of plasma endothelial microparticles were altered in MS patients following treatment over 12 months
Summary
Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the human central nervous system (CNS) characterized clinically by a relapsing-remitting course. MS manifests with development of demyelinating lesions which affect both gray and white matter [1,2] disruption of the blood brain barrier (BBB) and transendothelial migration of lymphocytes and macrophages across inflamed CNS endothelial monolayers appear to be among the earliest CNS and spinal. Upon activation by pro-inflammatory cytokines such as IFN-g or TNF-a, released by activated T-lymphocytes, endothelial cells shed small fragments of their membranes, known as endothelial microparticles (PMP). While it is difficult to evaluate inflammatory endothelial markers in MS in situ, microparticles may provide a remote ‘snapshot’ of the surface of inflamed endothelium and provide information on the extent of platelet and leukocyte activity in MS. We reported that various sub-species of PMP form complex with different leukocytes and by formation of such complexes, they promote the inflammatory process by facilitating transendothelial migration of the leukocytes [6]. We assessed the correlation among these sub-species of PMP and MRI parameters
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