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DNA Methylation-Bas...
DNA Methylation-Based Interferon Scores Associate With Sub-Phenotypes in Primary Sjögren's Syndrome
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- Imgenberg-Kreuz, Juliana (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi,Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
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- Sandling, Johanna K. (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi
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- Norheim, Katrine Braekke (författare)
- Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
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- Johnsen, Svein Joar Auglaend (författare)
- Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
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- Omdal, Roald (författare)
- Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
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- Syvänen, Ann-Christine, 1950- (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Svenungsson, Elisabet (författare)
- Karolinska Institutet
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Eloranta, Maija-Leena (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Nordmark, Gunnel (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2021-07-16
- 2021
- Engelska.
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Primary Sjogren's syndrome (pSS) is an autoimmune inflammatory disease with profound clinical heterogeneity, where excessive activation of the type I interferon (IFN) system is considered one of the key mechanisms in disease pathogenesis. Here we present a DNA methylation-based IFN system activation score (DNAm IFN score) and investigate its potential associations with sub-phenotypes of pSS. The study comprised 100 Swedish patients with pSS and 587 Swedish controls. For replication, 48 patients with pSS from Stavanger, Norway, were included. IFN scores were calculated from DNA methylation levels at the IFN-induced genes RSAD2, IFIT1 and IFI44L. A high DNAm IFN score, defined as > mean(controls) +2SD(controls) (IFN score > 4.4), was observed in 59% of pSS patients and in 4% of controls (p=1.3x10(-35)). Patients with a high DNAm IFN score were on average seven years younger at symptom onset (p=0.017) and at diagnosis (p=3x10(-3)). The DNAm IFN score levels were significantly higher in pSS positive for both SSA and SSB antibodies compared to SSA/SSB negative patients (p(discovery)=1.9x10(-8), p(replication)=7.8x10(-4)). In patients positive for both SSA subtypes Ro52 and Ro60, an increased score was identified compared to single positive patients (p=0.022). Analyzing the discovery and replication cohorts together, elevated DNAm IFN scores were observed in pSS with hypergammaglobulinemia (p=2x10(-8)) and low C4 (p=1.5x10(-3)) compared to patients without these manifestations. Patients < 70 years with ongoing lymphoma at DNA sampling or lymphoma at follow-up (n=7), presented an increased DNAm IFN score compared to pSS without lymphoma (p=0.025). In conclusion, the DNAm-based IFN score is a promising alternative to mRNA-based scores for identification of patients with activation of the IFN system and may be applied for patient stratification guiding treatment decisions, monitoring and inclusion in clinical trials.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- primary Sjogren's syndrome
- interferon
- DNA methylation
- autoimmunity
- interferonopathies
- precision medicine
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Omdal, Roald
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Rönnblom, Lars
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Eloranta, Maija- ...
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Nordmark, Gunnel
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