Contributions
Abstract: EP1470
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) which causes inflammation, demyelination and neurodegeneration. Different clinical subtypes as relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) have been described.
Circulating microRNAs (miRNAs), as an epigenetic mechanism of susceptibility to MS, might provide us useful biomarkers to identify disease subtypes, and also increasing knowledge about the biological processes involved in each one. The aim of this study was to identify a differential miRNA signature in PPMS patients.
Methods: Serum samples of 36 patients were collected (10 controls, 10 RRMS and 16 PPMS patients). Total RNA was extracted from serum using the mirVana PARIS RNA miRNA kit. TaqMan Advanced miRNA cDNA Synthesis Kit was used to retrotranscribe and preamplify circulating miRNAs and TaqMan OpenArray Human Advanced MicroRNA Panels were run to study the presence of 754 well-characterized human miRNAs.
OpenArray profiling data was filtered guaranteeing good quality of the detection and cut-off thresholds were set at 28 Cts. Data was normalised using geometric mean and differential expression analysis was performed by Kruskal-Wallis test.
Results: A total of 217 miRNAs were detected in at least 75% of serum samples, 175 of which presented Ct values equal or below 28. 13 significantly deregulated miRNAs between different groups were detected. Two miRNAs (miR-320b and miR-421) presented a singular signature in PPMS patients compared to controls and RRMS in the post hoc analysis.
While miR-320b levels were significantly down-regulated in PPMS patients compared to both controls and RRMS (p=0.035 and p=0.017 respectively), miR-421 expression was up-regulated (p=0.008 and p=0.015 respectively).
Pathway analyses showed that those miRNAs regulates the Hippo signalling pathway, a non-classical inflammatory pathway that seems to be involved in several chronic diseases such as neurodegeneration.
Conclusions: The results presented herein pointed out a deregulation of miR-320b and miR-421 as a key factor for PPMS development. However, further research must be addressed in order to determine the underlying mechanisms that are involved in the different subtypes of MS.
Disclosure: Muñoz-San Martín M reports no disclosures.
Robles-Cedeño R reports no disclosures.
Tomàs-Roig J reports no disclosures.
Celarain N reports no disclosures.
Gómez I reports no disclosures.
Perkal H reports no disclosures.
Quintana E reports no disclosures.
Lluís Ramió-Torrentà: has received compensation for consulting services and speaking honoraria from from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, Teva Pharmaceutical Industries Ltd, Almirall, Mylan.
Abstract: EP1470
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Genetics/Epigenetics
Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) which causes inflammation, demyelination and neurodegeneration. Different clinical subtypes as relapsing remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) have been described.
Circulating microRNAs (miRNAs), as an epigenetic mechanism of susceptibility to MS, might provide us useful biomarkers to identify disease subtypes, and also increasing knowledge about the biological processes involved in each one. The aim of this study was to identify a differential miRNA signature in PPMS patients.
Methods: Serum samples of 36 patients were collected (10 controls, 10 RRMS and 16 PPMS patients). Total RNA was extracted from serum using the mirVana PARIS RNA miRNA kit. TaqMan Advanced miRNA cDNA Synthesis Kit was used to retrotranscribe and preamplify circulating miRNAs and TaqMan OpenArray Human Advanced MicroRNA Panels were run to study the presence of 754 well-characterized human miRNAs.
OpenArray profiling data was filtered guaranteeing good quality of the detection and cut-off thresholds were set at 28 Cts. Data was normalised using geometric mean and differential expression analysis was performed by Kruskal-Wallis test.
Results: A total of 217 miRNAs were detected in at least 75% of serum samples, 175 of which presented Ct values equal or below 28. 13 significantly deregulated miRNAs between different groups were detected. Two miRNAs (miR-320b and miR-421) presented a singular signature in PPMS patients compared to controls and RRMS in the post hoc analysis.
While miR-320b levels were significantly down-regulated in PPMS patients compared to both controls and RRMS (p=0.035 and p=0.017 respectively), miR-421 expression was up-regulated (p=0.008 and p=0.015 respectively).
Pathway analyses showed that those miRNAs regulates the Hippo signalling pathway, a non-classical inflammatory pathway that seems to be involved in several chronic diseases such as neurodegeneration.
Conclusions: The results presented herein pointed out a deregulation of miR-320b and miR-421 as a key factor for PPMS development. However, further research must be addressed in order to determine the underlying mechanisms that are involved in the different subtypes of MS.
Disclosure: Muñoz-San Martín M reports no disclosures.
Robles-Cedeño R reports no disclosures.
Tomàs-Roig J reports no disclosures.
Celarain N reports no disclosures.
Gómez I reports no disclosures.
Perkal H reports no disclosures.
Quintana E reports no disclosures.
Lluís Ramió-Torrentà: has received compensation for consulting services and speaking honoraria from from Biogen, Novartis, Bayer, Merck, Sanofi, Genzyme, Teva Pharmaceutical Industries Ltd, Almirall, Mylan.