Abstract Details

Title Circular RNA of Blood Leukocytes Contribute To Proinflammatory Changes in Relapsing-Remitting Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S55 - MS Basic Science (4:14 PM-4:25 PM)

Poster/Presentation
Number 005

Background CircRNA are a novel class of non-protein coding RNAs. Recent works have revealed that circRNA are abundant and stable within immune cells with expression pattern correlating to a tissue of origin. It has been suggested that circRNA regulate microRNA (miRNA) and thus represent a control mechanism over miRNA circuit involved in immunoregulation. The expression and function of circRNA in multiple sclerosis (MS) was not studied so far.

Objective To assess and compare the circular RNA (circRNA) content of peripheral blood mononuclear cells (PBMCs) from remitting relapsing MS (RRMS) patients in relapse and remission as a potential biomarkers of disease activity.

Design/Methods In the present study differential expression of 13,617 human circRNA total RNA in PBMC of 10 RRMS patients during relapse, 10 in remission and 10 healthy controls was performed with a high-throughput microarrays. The impact of the differentially expressed circRNA in the high activity RRMS patients were identified with a circRNA-microRNA target prediction software. In addition, Gene Ontology enrichment analysis was applied to identify the most significant putative pathways affected by the highlighted circRNA-microRNA.

Results A detailed analysis of RRMS samples versus control group revealed 541 circRNA significantly upregulated and 68 downregulated in MS (p<0.05, FDR<0.05). The miRNA prediction analysis highlighted 65 different miRNA downregulated and only one miRNA upregulated by circRNA identified in RRMS samples. Finally, the analysis of the protein coding transcripts affected by these circRNA elucidated a pathway significantly linked with STAT3, a critical transcription factor determining the polarization of immune response toward Th17.

Conclusions circRNA measurement might provide new biomarkers for RR MS patients as well as contribute to an understanding of a disease pathogenesis.

Authors/Disclosures
Marcin P. Mycko, MD (Medical University of Lodz, Department of Neurology) PRESENTER	No disclosure on file
	No disclosure on file
Krzysztof W. Selmaj (University of Warmia and Mazury)	Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Krzysztof W. Selmaj has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.

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