Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints.
Adult
Aged
Aged, 80 and over
Arthralgia
/ genetics
Arthritis, Rheumatoid
/ complications
Arthroscopy
Biopsy
/ methods
DNA Methylation
/ immunology
Epigenesis, Genetic
/ immunology
Female
Humans
Male
Middle Aged
RNA-Seq
Severity of Illness Index
Synovial Membrane
/ immunology
Whole Genome Sequencing
Young Adult
DNA methylation
arthralgia
multi-omics analyses
rheumatoid arthritis
synovial biopsies
target identification
transcriptomics
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
01
2021
accepted:
25
03
2021
entrez:
10
5
2021
pubmed:
11
5
2021
medline:
25
9
2021
Statut:
epublish
Résumé
In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approach where we investigated differences at the level of DNA methylation and gene expression in relation to disease pathogenesis. We performed concurrent whole-genome bisulphite sequencing and RNA-Sequencing on synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66), with patients with SJC66 of 9 or more displaying separation from the rest. Interrogating these observed differences revealed activation of the immune response as well as dysregulation of cell adhesion pathways at the level of both DNA methylation and gene expression. We observed differences for 59 genes in particular at the level of both transcript expression and DNA methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of changes associated with disease spread in arthralgia and RA patients, and point to novel candidate targets for the treatment of the disease.
Identifiants
pubmed: 33968050
doi: 10.3389/fimmu.2021.651475
pmc: PMC8100206
doi:
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
651475Informations de copyright
Copyright © 2021 Li Yim, Ferrero, Maratou, Lewis, Royal, Tough, Larminie, Mannens, Henneman, de Jonge, van de Sande, Gerlag, Prinjha and Tak.
Déclaration de conflit d'intérêts
AL, KM, GR, HL, DT, CL, DG, and RP were employed by GSK when this study was conducted. EF and PT were employed by Novartis and Candel Therapeutics when this study was conducted, respectively. WJ was financially supported by GSK and Mead Johnson. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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