Karolinska Institutet
Department of Medicine

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0136 - Profiling of small non-coding RNAs across cellular and biofluidĀ compartments in patients with Multiple Sclerosis (ID 1195)

Speakers
Presentation Number
P0136
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Small non-coding RNAs (sncRNAs) are important regulators of gene expression at the transcriptional and post-transcriptional levels in various biological contexts, such as regulation of immune system functions, homeostasis, and autoimmunity development. While the role of microRNAs (miRNAs) in multiple sclerosis (MS) has attained major interest, studies investigating other sncRNA classes, especially in the target central nervous system compartment, are still scarce.

Objectives

We aimed to perform a comprehensive, comparative analysis of all classes of sncRNAs in matching peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from MS patients and controls.

Methods

23 relapsing-remitting (RRMS, n=12 in relapse, n=11 in remission), 6 secondary progressive (SPMS) MS patients and 16 non-inflammatory and inflammatory neurological disease controls (NINDC, n=11; INDC, n=5) were included in the analysis. We utilized Small-seq (Faridani et al., Nat Biotechnol. 2016) to quantify sncRNA transcripts.

Results

We observed distinct and variable profiles of sncRNA classes across all analyzed cellular and biofluid compartments. While miRNAs were the most abundant class of sncRNAs in PBMCs and plasma, transfer RNAs represented the most abundant class in CSF cells and cell-free CSF. Furthermore, we observed an opposing quantitative pattern of small nuclear, nucleolar, transfer RNAs, and miRNAs changes between the blood and CNS compartments. In CSF cells, 133/133 and 115/117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65/67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. These findings underscore the importance of including both the peripheral and intrathecal compartments in studies investigating the role of sncRNAs in MS.

Conclusions

Our findings demonstrate widespread alterations of several classes of sncRNAs, particularly during the relapse phase in CSF cells. Genome-wide small non-coding RNA profiling provides therefore an informative moleculer panel for addressing MS pathogenesis, where further research may lead to the identification of novel biomarkers and possible treatment targets.

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