Karolinska Institute
Clinical Neuroscience

Author Of 1 Presentation

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.

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