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Shared and Unique P...
Shared and Unique Patterns of DNA Methylation in Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
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- Imgenberg-Kreuz, Juliana (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi,Uppsala Univ, Sweden
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- Carlsson Almlöf, Jonas (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär medicin,Uppsala Univ, Sweden
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- Leonard, Dag, 1975- (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Sjöwall, Christopher (författare)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Syvänen, Ann-Christine, 1950- (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Sandling, Johanna K. (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi,Uppsala Univ, Sweden
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sect Rheumatol, Uppsala, Sweden;Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden
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(creator_code:org_t)
- 2019-07-30
- 2019
- Engelska.
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
- Relaterad länk:
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https://doi.org/10.3...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Objectives: To performa cross-comparative analysis of DNA methylation in patients with systemic lupus erythematosus (SLE), patients with primary Sjogren's syndrome (pSS), and healthy controls addressing the question of epigenetic sharing and aiming to detect disease-specific alterations. Methods: DNA extracted from peripheral blood from 347 cases with SLE, 100 cases with pSS, and 400 healthy controls were analyzed on the Human Methylation 450k array, targeting 485,000 CpG sites across the genome. A linear regression model including age, sex, and blood cell type distribution as covariates was fitted, and association p-values were Bonferroni corrected. A random forest machine learning classifier was designed for prediction of disease status based on DNA methylation data. Results: We established a combined set of 4,945 shared differentially methylated CpG sites (DMCs) in SLE and pSS compared to controls. In pSS, hypomethylation at type I interferon induced genes was mainly driven by patients who were positive for Ro/SSA and/or La/SSB autoantibodies. Analysis of differential methylation between SLE and pSS identified 2,244 DMCs with a majority of sites showing decreased methylation in SLE compared to pSS. The random forest classifier demonstrated good performance in discerning between disease status with an area under the curve (AUC) between 0.83 and 0.96. Conclusions: The majority of differential DNA methylation is shared between SLE and pSS, however, important quantitative differences exist. Our data highlight neutrophil dysregulation as a shared mechanism, emphasizing the role of neutrophils in the pathogenesis of systemic autoimmune diseases. The current study provides evidence for genes and molecular pathways driving common and disease-specific pathogenic mechanisms.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- systemic lupus erythematosus
- primary Sjogren's syndrome
- DNA methylation
- EWAS
- epigenetics
- autoimmunity
- type I interferon
- random forest
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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