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 Article Swipe
Andrew Y. F. Li Yim
,
Enrico Ferrero
,
Klio Maratou
,
Huw D. Lewis
,
George C. Royal
,
David F. Tough
,
Chris Larminie
,
Marcel M. A. M. Mannens
,
Peter Henneman
,
Wouter J. de Jonge
,
M. G. H. Van de Sande
,
Daniëlle M. Gerlag
,
Rab K. Prinjha
,
Paul P. Tak
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2021.651475
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2021.651475
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.
Related Topics
Concepts
DNA methylation
Rheumatoid arthritis
Gene
Arthritis
Methylation
Gene expression
Gene expression profiling
Bisulfite sequencing
Immunology
Pathogenesis
Biology
Medicine
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2021.651475
- OA Status
- gold
- Cited By
- 13
- References
- 80
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3161011426
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3161011426Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2021.651475Digital Object Identifier
- Title
-
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 JointsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-04-22Full publication date if available
- Authors
-
Andrew Y. F. Li Yim, Enrico Ferrero, Klio Maratou, Huw D. Lewis, George C. Royal, David F. Tough, Chris Larminie, Marcel M. A. M. Mannens, Peter Henneman, Wouter J. de Jonge, M. G. H. Van de Sande, Daniëlle M. Gerlag, Rab K. Prinjha, Paul P. TakList of authors in order
- Landing page
-
https://doi.org/10.3389/fimmu.2021.651475Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.3389/fimmu.2021.651475Direct OA link when available
- Concepts
-
DNA methylation, Rheumatoid arthritis, Gene, Arthritis, Methylation, Gene expression, Gene expression profiling, Bisulfite sequencing, Immunology, Pathogenesis, Biology, Medicine, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
13Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 2, 2023: 4, 2022: 4, 2021: 1Per-year citation counts (last 5 years)
- References (count)
-
80Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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