Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren's syndrome

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Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren's syndrome

Björk, Albin (author): Karolinska Institutet

Andersson, Elina Richardsdotter (author): Karolinska Institutet

Imgenberg-Kreuz, Juliana (author): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi

Thorlacius, Gudny Ella (author): Karolinska Institutet

Mofors, Johannes (author): Karolinska Institutet

Syvänen, Ann-Christine, 1950- (author): Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab

Kvarnström, Marika (author): Karolinska Institutet

Nordmark, Gunnel (author): Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab

Wahren-Herlenius, Marie (author): Karolinska Institutet

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(creator_code:org_t)

2020-01-07
2020
English.
In: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 6:1

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://rmdopen.bmj....; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Objective: Standard assessment of interferon (IFN) system activity in systemic rheumatic diseases depends on the availability of RNA samples. In this study, we describe and evaluate alternative methods using plasma, serum and DNA samples, exemplified in the IFN-driven disease primary Sjogren's syndrome (pSS).Methods: Patients with pSS seropositive or negative for anti-SSA/SSB and controls were included. Protein-based IFN (pIFN) scores were calculated from levels of PD-1, CXCL9 and CXCL10. DNA methylation-based (DNAm) IFN scores were calculated from DNAm levels at RSAD2, IFIT1 and IFI44L. Scores were compared with mRNA-based IFN scores measured by quantitative PCR (qPCR), Nanostring or RNA sequencing (RNAseq).Results: mRNA-based IFN scores displayed strong correlations between B cells and monocytes (r=0.93 and 0.95, p<0.0001) and between qPCR and Nanostring measurements (r=0.92 and 0.92, p<0.0001). The pIFN score in plasma and serum was higher in patients compared with controls (p<0.0001) and correlated well with mRNA-based IFN scores (r=0.62-0.79, p<0.0001), as well as with each other (r=0.94, p<0.0001). Concordance of classification as 'high' or 'low' IFN signature between the pIFN score and mRNA-based IFN scores ranged from 79.5% to 88.6%, and the pIFN score was effective at classifying patients and controls (area under the curve, AUC=0.89-0.93, p<0.0001). The DNAm IFN score showed strong correlation to the RNAseq IFN score (r=0.84, p<0.0001) and performed well in classifying patients and controls (AUC=0.96, p<0.0001).Conclusions: We describe novel methods of assessing IFN system activity in plasma, serum or DNA samples, which may prove particularly valuable in studies where RNA samples are not available.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

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By the author/editor: Björk, Albin; Andersson, Elina ...; Imgenberg-Kreuz, ...; Thorlacius, Gudn ...; Mofors, Johannes; Syvänen, Ann-Chr ...; show more...; Kvarnström, Mari ...; Nordmark, Gunnel; Wahren-Herlenius ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

Articles in the publication: RMD Open

By the university: Uppsala University; Karolinska Institutet

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