Contributions
Abstract: P590
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Cognitive impairment is one of the most frequent symptoms in pediatric MS (PedMS) that may severely impact quality of life and school performances. Molecular markers predictive of its occurrence and progression have not been identified, so far.
Objectives: To assess the expression levels of peripheral miRNAs and mRNAs by a Next-Generation Sequencing (NGS) approach, and to uncover molecular pathway/s associated with PedMS.
Methods: PedMS patients underwent clinical/neuropsychological evaluations; as neurological controls, age-matched Attention Deficit Hyperactive Disorder (ADHD) patients were included. Total RNA extraction from peripheral blood was followed by NGS, producing small-RNA and total-RNA reads. Small-RNA reads were analyzed by an in-house bioinformatics platform (nc-aReNA) that implements a modular analysis pipeline able to identify/classify sequenced reads by a non-coding reference database; statistics based on p-value identify changes of expression profiles. To test the association between miRNAs expression, their mRNAs targets and changes of cognitive abilities, total-RNA reads were submitted to quantification for differential gene expression (DE).
Results: 16 PedMS (mean age 14.8+/-2.8 years, mean age onset=12.3+/-3.7 years, median EDSS=2.5) and 11 age-matched ADHD patients were sequenced. The comparison of miRNAs expression levels between PedMS and ADHD revealed significant differences in 49 miRNAs (p< 0.05). MiR-15a-5p, miR-15b-3p, miR-16-5p miR-17-3p/5p, miR-22-3p, miR-23a-3p, miR-26a-5p, miR-27b-3p, miR-93-5p, miR-106b-5p, miR-128-3p, miR-130a-3p, miR-144-5p, miR-148a-3p, miR-221-3p miR-223-3p, miR-486-5p, miR-532-5p and Let-7 family have been already reported associated with adult MS. Six PedMS (37.5%) resulted cognitively impaired (CI): the comparison of miRNAs expression levels between CI and cognitively preserved (CP) PedMS did not show significant differences. The comparison of RNA-Seq reads between CI and CP PedMS identified DE genes (p< 0.05); of note, EIF4G1 and NLRP2 have been reported associated with other neurodegenerative diseases, DBNDD1 was found influencing several cognitive functions.
Conclusions: These results confirmed the involvement of miRNAs in PedMS and identified some interesting genes associated with CI-PedMS; a different signature seems to characterize CI-ADHD. A longitudinal evaluation on a larger sample size will allow to assess the predictive value of these markers on cognitive dysfunction progression.
Disclosure: This study is fully supported by FISM - Fondazione Italiana Sclerosi Multipla (Grant cod. 2014/R/10; Principal Investigator: Dr. Maria Liguori).
Dr. Maria Liguori has nothing to disclosure
Dr. Nicoletta Nuzziello has nothing to disclosure
Dr. Marta Simone has nothing to disclosure
Dr. Vito Flavio Licciulli has nothing to disclosure
Dr. Rosa Gemma Viterbo has nothing to disclosure
Dr. Nicola Ancona has nothing to disclosure
Dr. Arianna Consiglio has nothing to disclosure
Dr. Teresa Creanza has nothing to disclosure
Dr. Giorgio Decaro has nothing to disclosure
Dr. Sabino Liuni has nothing to disclosure
Prof. Lucia Margari has nothing to disclosure
Prof. Maria Trojano has served on scientific Advisory Boards for Biogen Idec, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants for her Institution from Biogen-Idec, Merck-Serono and Novartis.
Abstract: P590
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Cognitive impairment is one of the most frequent symptoms in pediatric MS (PedMS) that may severely impact quality of life and school performances. Molecular markers predictive of its occurrence and progression have not been identified, so far.
Objectives: To assess the expression levels of peripheral miRNAs and mRNAs by a Next-Generation Sequencing (NGS) approach, and to uncover molecular pathway/s associated with PedMS.
Methods: PedMS patients underwent clinical/neuropsychological evaluations; as neurological controls, age-matched Attention Deficit Hyperactive Disorder (ADHD) patients were included. Total RNA extraction from peripheral blood was followed by NGS, producing small-RNA and total-RNA reads. Small-RNA reads were analyzed by an in-house bioinformatics platform (nc-aReNA) that implements a modular analysis pipeline able to identify/classify sequenced reads by a non-coding reference database; statistics based on p-value identify changes of expression profiles. To test the association between miRNAs expression, their mRNAs targets and changes of cognitive abilities, total-RNA reads were submitted to quantification for differential gene expression (DE).
Results: 16 PedMS (mean age 14.8+/-2.8 years, mean age onset=12.3+/-3.7 years, median EDSS=2.5) and 11 age-matched ADHD patients were sequenced. The comparison of miRNAs expression levels between PedMS and ADHD revealed significant differences in 49 miRNAs (p< 0.05). MiR-15a-5p, miR-15b-3p, miR-16-5p miR-17-3p/5p, miR-22-3p, miR-23a-3p, miR-26a-5p, miR-27b-3p, miR-93-5p, miR-106b-5p, miR-128-3p, miR-130a-3p, miR-144-5p, miR-148a-3p, miR-221-3p miR-223-3p, miR-486-5p, miR-532-5p and Let-7 family have been already reported associated with adult MS. Six PedMS (37.5%) resulted cognitively impaired (CI): the comparison of miRNAs expression levels between CI and cognitively preserved (CP) PedMS did not show significant differences. The comparison of RNA-Seq reads between CI and CP PedMS identified DE genes (p< 0.05); of note, EIF4G1 and NLRP2 have been reported associated with other neurodegenerative diseases, DBNDD1 was found influencing several cognitive functions.
Conclusions: These results confirmed the involvement of miRNAs in PedMS and identified some interesting genes associated with CI-PedMS; a different signature seems to characterize CI-ADHD. A longitudinal evaluation on a larger sample size will allow to assess the predictive value of these markers on cognitive dysfunction progression.
Disclosure: This study is fully supported by FISM - Fondazione Italiana Sclerosi Multipla (Grant cod. 2014/R/10; Principal Investigator: Dr. Maria Liguori).
Dr. Maria Liguori has nothing to disclosure
Dr. Nicoletta Nuzziello has nothing to disclosure
Dr. Marta Simone has nothing to disclosure
Dr. Vito Flavio Licciulli has nothing to disclosure
Dr. Rosa Gemma Viterbo has nothing to disclosure
Dr. Nicola Ancona has nothing to disclosure
Dr. Arianna Consiglio has nothing to disclosure
Dr. Teresa Creanza has nothing to disclosure
Dr. Giorgio Decaro has nothing to disclosure
Dr. Sabino Liuni has nothing to disclosure
Prof. Lucia Margari has nothing to disclosure
Prof. Maria Trojano has served on scientific Advisory Boards for Biogen Idec, Novartis, Almirall, Roche and Genzyme; has received speaker honoraria from Biogen-Idec, Bayer-Schering, Sanofi Aventis, Merck-Serono, Teva, Genzyme, Almirall and Novartis; has received research grants for her Institution from Biogen-Idec, Merck-Serono and Novartis.