The effects of high dose interferon-β1a on plasma microparticles: Correlation with MRI parameters

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.

Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility

“…Similarly, other groups have reported that MCAM EMPs do not reflect endothelial damage induced by INFß-1, although PECAM EMPs do 35. MCAM is also expressed on a subset of T- and B-lymphocytes, NK cells36 and pericytes 37.…”

Blood circulating microparticle species in relapsing–remitting and secondary progressive multiple sclerosis. A case–control, cross sectional study with conventional MRI and advanced iron content imaging outcomes

“…Several endothelial and platelet ECAMs have now been described as MP markers in MS including CD51/CD61 (αV/β3-integrin), CD31 (platelet endothelial cell adhesion molecule-1) [7] and CD54 (intercellular adhesion molecule-1/ICAM-1) [7]. CD31 is an immunoglobulin-superfamily ECAM constitutively expressed on apical and junctional endothelial surfaces, and on platelets, myeloid cells and lymphocytes.…”

“…CD31 is an immunoglobulin-superfamily ECAM constitutively expressed on apical and junctional endothelial surfaces, and on platelets, myeloid cells and lymphocytes. CD31 + MPs are released during MS exacerbations [4]; and appear to correlate with early changes in BBB disruption and axonal injury, often abating during remission and therapy [7]. Another MP marker, CD51 (integrin αV) forms several complexes which bind fibronectin and vitronectin and regulates vascular structure and stability [8].…”

“…Complexed with CD61, they form integrin αV/β3 which is expressed by endothelial cells, platelets but also macrophages and neutrophils. CD51 + /61 + MPs increase after MS onset [4] but does not diminish during remission or therapy [7]. MP profiling has thus suggested CD51 + /61 + as a vascular marker of underlying MS disease.…”

Molecular Biomarkers in Multiple Sclerosis

“…One step in the right direction would be, that more researchers would appreciate the possibility to upload their -even though small-data sets with expression data and clinical data. This would enable researchers to utilize these data for [37] pNF-H (+) Cellular [93,94] plasma endothelial microparticles (+) miRNA [90] hsa-miR-1826 (+) hsa-miR-572 (+) hsa-miR-1979 (-) hsa-miR-614 (+) hsa-miR-22 (+) hsa-miR-648 (+) Serum and PBMC miRNA [25,90] hsa-miR-422a (+) PBMC miRNA [25][26][27]71,72,89] hsa-miR-19b (CD4+CD25+ cells) (+) hsa-miR-17-5p (+) hsa-miR-25 (CD4+CD25+ cells) (+) hsa-miR-18-5p (+) hsa-miR-1275 (+) hsa-miR-186-5p (-) hsa-miR-145-5p (+) hsa-miR-20a-5p (+) hsa-miR-491-5p (+) hsa-miR-20b-5p (+) hsa-miR-584-5p (+) hsa-miR-223-3p (+) hsa-miR-664-3p (+) hsa-miR-142-3p (+) mRNA [1] ATP7A ( Fas/FasL mRNA [5] ILT3 (-; mono.) miRNA [25,71,72] hsa-miR-18b (+) hsa-miR-599 (+) hsa-miR-96-5p (+; remission) Disease activity and treatment response…”