uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Shared and Unique Patterns of DNA Methylation in Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.ORCID-id: 0000-0002-7230-8990
Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Rheumatol, Linkoping, Sweden.
Visa övriga samt affilieringar
2019 (Engelska)Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, artikel-id 1686Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
FRONTIERS MEDIA SA , 2019. Vol. 10, artikel-id 1686
Nyckelord [en]
systemic lupus erythematosus, primary Sjogren's syndrome, DNA methylation, EWAS, epigenetics, autoimmunity, type I interferon, random forest
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
URN: urn:nbn:se:uu:diva-391357DOI: 10.3389/fimmu.2019.01686ISI: 000477805800001PubMedID: 31428085OAI: oai:DiVA.org:uu-391357DiVA, id: diva2:1354240
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, KAW 2011.0073Vetenskapsrådet, VR-MH Dnr 521-2014-2263Vetenskapsrådet, Dnr 2018-02399Vetenskapsrådet, Dnr 2016-01982VetenskapsrådetKnut och Alice Wallenbergs StiftelseTillgänglig från: 2019-09-24 Skapad: 2019-09-24 Senast uppdaterad: 2019-09-24Bibliografiskt granskad

Open Access i DiVA

fulltext(2283 kB)72 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2283 kBChecksumma SHA-512
7758ec4325c3a345d5dd016558fea4b76d11b30bb91982404818dced887f91db3b73c15a172bceb4e76b3851bf6f0bbf3f2035f3bee72c06cfa6c308b0bdbba8
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Imgenberg-Kreuz, JulianaCarlsson Almlöf, JonasLeonard, DagSyvänen, Ann-ChristineRönnblom, LarsSandling, Johanna K.Nordmark, Gunnel

Sök vidare i DiVA

Av författaren/redaktören
Imgenberg-Kreuz, JulianaCarlsson Almlöf, JonasLeonard, DagSyvänen, Ann-ChristineRönnblom, LarsSandling, Johanna K.Nordmark, Gunnel
Av organisationen
Science for Life Laboratory, SciLifeLabReumatologiMolekylär medicin
I samma tidskrift
Frontiers in Immunology
Reumatologi och inflammation

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 72 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 82 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf