Contributions
Abstract: EP1473
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: MicroRNAs are small non-coding RNA molecules that regulate the post-transcriptional expression of several genes involved in the pathogenesis of MS. In MS, several microRNAs are dysregulated in the brain, various peripheral immune cells, and biological fluids. Consequently, microRNAs may serve as potential biomarkers to help diagnose MS, determine disease progression, and predict the efficacy of disease-modifying therapies.
Objective: The objective of this study was to identify and correlate circulating microRNA expression in plasma and immune cell subsets in relapsing-remitting MS (RRMS) patients. We also assessed how disease-modifying therapies (DMTs), particularly oral therapies, may influence microRNA expression in patient populations.
Methods: Peripheral blood was drawn from consenting age and sex matched healthy controls and RRMS patients either untreated or treated with the oral DMTs, including dimethyl fumarate or teriflunomide. Plasma was collected following centrifugation of EDTA-treated whole blood. Additionally, PBMCs were collected from blood following Ficoll density centrifugation and subsequent isolation of immune cells by magnetic-activated cell sorting. RNA was isolated and subjected to reverse-transcriptase quantitative PCR (RT-qPCR) for quantification of microRNA content using TaqMan microRNA assays. MicroRNAs were selected based on their previously documented roles in inflammation and their ability to influence MS disease activity.
Results: In plasma, our results demonstrated a significant decrease of miR-19a levels in MS patients vs. healthy controls. Analysis of CD14+ microRNA expression demonstrated increases in microRNAs -146b, -223 and -365a in MS patients compared to controls. Of the oral DMTs assessed, teriflunomide normalized the expression of several CD14+ microRNAs analyzed. No significant correlations were found between plasma and CD14+ cell microRNA content.
Conclusion: Our results indicate that microRNAs are dysregulated in RRMS patient plasma and peripheral immune cell populations, which may participate in disease activity or serve as disease biomarkers. Given the lack of correlations found between microRNA expression in various immune cell subsets and plasma, our results emphasize that the expression cell specific microRNAs will be critical for elucidating future MS biomarkers.
Disclosure:
Dylan A. Galloway: nothing to disclose.
Kathy Murphy-Peddle: nothing to disclose.
Mark Stefanelli: nothing to disclose.
Craig S. Moore: nothing to disclose.
Abstract: EP1473
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: MicroRNAs are small non-coding RNA molecules that regulate the post-transcriptional expression of several genes involved in the pathogenesis of MS. In MS, several microRNAs are dysregulated in the brain, various peripheral immune cells, and biological fluids. Consequently, microRNAs may serve as potential biomarkers to help diagnose MS, determine disease progression, and predict the efficacy of disease-modifying therapies.
Objective: The objective of this study was to identify and correlate circulating microRNA expression in plasma and immune cell subsets in relapsing-remitting MS (RRMS) patients. We also assessed how disease-modifying therapies (DMTs), particularly oral therapies, may influence microRNA expression in patient populations.
Methods: Peripheral blood was drawn from consenting age and sex matched healthy controls and RRMS patients either untreated or treated with the oral DMTs, including dimethyl fumarate or teriflunomide. Plasma was collected following centrifugation of EDTA-treated whole blood. Additionally, PBMCs were collected from blood following Ficoll density centrifugation and subsequent isolation of immune cells by magnetic-activated cell sorting. RNA was isolated and subjected to reverse-transcriptase quantitative PCR (RT-qPCR) for quantification of microRNA content using TaqMan microRNA assays. MicroRNAs were selected based on their previously documented roles in inflammation and their ability to influence MS disease activity.
Results: In plasma, our results demonstrated a significant decrease of miR-19a levels in MS patients vs. healthy controls. Analysis of CD14+ microRNA expression demonstrated increases in microRNAs -146b, -223 and -365a in MS patients compared to controls. Of the oral DMTs assessed, teriflunomide normalized the expression of several CD14+ microRNAs analyzed. No significant correlations were found between plasma and CD14+ cell microRNA content.
Conclusion: Our results indicate that microRNAs are dysregulated in RRMS patient plasma and peripheral immune cell populations, which may participate in disease activity or serve as disease biomarkers. Given the lack of correlations found between microRNA expression in various immune cell subsets and plasma, our results emphasize that the expression cell specific microRNAs will be critical for elucidating future MS biomarkers.
Disclosure:
Dylan A. Galloway: nothing to disclose.
Kathy Murphy-Peddle: nothing to disclose.
Mark Stefanelli: nothing to disclose.
Craig S. Moore: nothing to disclose.