Contributions
Abstract: EP1602
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: MicroRNAs are small non-coding RNA molecules that regulate the expression of genes post-transcriptionally. In the context of MS, several microRNAs are dysregulated in both immune cells and plasma. Identifying altered microRNA expression patterns between MS patient prescribed various disease-modifying therapies (DMTs) may further elucidate the mechanism(s) of action for DMTs and assist in predicting an individual's immune and clinical response to a particular therapy.
Objective: The objective of this study was to identify whether DMTs influence the dysregulated microRNA expression that is observed in the immune cells (T cells, B cells and monocytes) of MS patients. Furthermore, microRNA expression in both plasma and specific immune cell subsets will be correlated with clinical disability.
Methods: Plasma and peripheral blood mononuclear cells were collected from age and sex-matched healthy controls and relapsing-remitting MS patients, including both treatment naïve and patients prescribed specific DMTs. Isolation of CD19+ B cells, CD14+ monocytes, CD8+ T cells and CD4+ T cells was performed by magnetic-activated cell sorting. RNA was isolated from plasma and individual cell subsets. qPCR was used to quantify the expression of miR-223, -155, -146a, -146b, -19a and -365. Expression was correlated with EDSS.
Results: A significant decrease in miR-19a was observed in the plasma of MS patients vs healthy controls and was independent of treatment. Compared to healthy controls, analysis of CD14+ microRNA demonstrated increases in mir -146b, -223 and -365a in MS patients; teriflunomide normalized the expression of all microRNAs within the CD14+ population. In CD4+ and CD8+ T cells from RRMS patients, mir-155 was increased, however teriflunomide and dimethyl fumarate only normalized miR-155 expression within helper, but not cytotoxic, T cells. No significant differences were found between healthy control and MS patient B cells, however miR-223 was upregulated by treatment with DMF. No microRNAs were significantly correlated with EDSS.
Conclusion: Our results indicate that microRNAs are dysregulated in several immune cell subsets of RRMS patients and can be significantly altered by DMTs. Unique cellular microRNA expression patterns may therefore serve as potential disease biomarkers and/or elucidate further mechanism(s) of action.
Disclosure:
Galloway D.A: Nothing to disclose
Murphy-Peddle K: Nothing to disclose
Stefanelli M: Nothing to disclose
Moore C.S: has received speaker honoraria from Biogen, EMD Serono, and Roche/Genentech.
Abstract: EP1602
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: MicroRNAs are small non-coding RNA molecules that regulate the expression of genes post-transcriptionally. In the context of MS, several microRNAs are dysregulated in both immune cells and plasma. Identifying altered microRNA expression patterns between MS patient prescribed various disease-modifying therapies (DMTs) may further elucidate the mechanism(s) of action for DMTs and assist in predicting an individual's immune and clinical response to a particular therapy.
Objective: The objective of this study was to identify whether DMTs influence the dysregulated microRNA expression that is observed in the immune cells (T cells, B cells and monocytes) of MS patients. Furthermore, microRNA expression in both plasma and specific immune cell subsets will be correlated with clinical disability.
Methods: Plasma and peripheral blood mononuclear cells were collected from age and sex-matched healthy controls and relapsing-remitting MS patients, including both treatment naïve and patients prescribed specific DMTs. Isolation of CD19+ B cells, CD14+ monocytes, CD8+ T cells and CD4+ T cells was performed by magnetic-activated cell sorting. RNA was isolated from plasma and individual cell subsets. qPCR was used to quantify the expression of miR-223, -155, -146a, -146b, -19a and -365. Expression was correlated with EDSS.
Results: A significant decrease in miR-19a was observed in the plasma of MS patients vs healthy controls and was independent of treatment. Compared to healthy controls, analysis of CD14+ microRNA demonstrated increases in mir -146b, -223 and -365a in MS patients; teriflunomide normalized the expression of all microRNAs within the CD14+ population. In CD4+ and CD8+ T cells from RRMS patients, mir-155 was increased, however teriflunomide and dimethyl fumarate only normalized miR-155 expression within helper, but not cytotoxic, T cells. No significant differences were found between healthy control and MS patient B cells, however miR-223 was upregulated by treatment with DMF. No microRNAs were significantly correlated with EDSS.
Conclusion: Our results indicate that microRNAs are dysregulated in several immune cell subsets of RRMS patients and can be significantly altered by DMTs. Unique cellular microRNA expression patterns may therefore serve as potential disease biomarkers and/or elucidate further mechanism(s) of action.
Disclosure:
Galloway D.A: Nothing to disclose
Murphy-Peddle K: Nothing to disclose
Stefanelli M: Nothing to disclose
Moore C.S: has received speaker honoraria from Biogen, EMD Serono, and Roche/Genentech.