Karolinska Institute
Department of Medicine

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0136 - Profiling of small non-coding RNAs across cellular and biofluid 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.

Collapse
Pathogenesis – Immunology Poster Presentation

P0979 - Methylome and transcriptome signature of bronchoalveolar cells from Multiple Sclerosis patients in relation to smoking (ID 1145)

Speakers
Presentation Number
P0979
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

Despite compelling evidence of the contribution of smoking in MS susceptibility and progression, little is known about smoking-associated changes in the primary exposed lung cells of patients.

Objectives

We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HC).

Methods

We profiled DNA methylation in BAL cells from female MS (n=17) and HC (n=22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers.

Results

The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers MS patients compared to HC suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. This molecular signature was consistent with findings from animal studies of MS-like disease.

Conclusions

Our study provides insights into the molecular impact of smoking on lung inflammation and the immunopathogenesis of MS.

Collapse