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

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 Sjögren’s syndr...

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Autores principales: Björk, Albin, Richardsdotter Andersson, Elina, Imgenberg-Kreuz, Juliana, Thorlacius, Gudny Ella, Mofors, Johannes, Syvänen, Ann-Christine, Kvarnström, Marika, Nordmark, Gunnel, Wahren-Herlenius, Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046975/
https://www.ncbi.nlm.nih.gov/pubmed/31958277
http://dx.doi.org/10.1136/rmdopen-2019-000995
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author Björk, Albin
Richardsdotter Andersson, Elina
Imgenberg-Kreuz, Juliana
Thorlacius, Gudny Ella
Mofors, Johannes
Syvänen, Ann-Christine
Kvarnström, Marika
Nordmark, Gunnel
Wahren-Herlenius, Marie
author_facet Björk, Albin
Richardsdotter Andersson, Elina
Imgenberg-Kreuz, Juliana
Thorlacius, Gudny Ella
Mofors, Johannes
Syvänen, Ann-Christine
Kvarnström, Marika
Nordmark, Gunnel
Wahren-Herlenius, Marie
author_sort Björk, Albin
collection PubMed
description 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 Sjögren’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.
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spelling pubmed-70469752020-03-09 Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome Björk, Albin Richardsdotter Andersson, Elina Imgenberg-Kreuz, Juliana Thorlacius, Gudny Ella Mofors, Johannes Syvänen, Ann-Christine Kvarnström, Marika Nordmark, Gunnel Wahren-Herlenius, Marie RMD Open Sjögren Syndrome 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 Sjögren’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. BMJ Publishing Group 2020-01-07 /pmc/articles/PMC7046975/ /pubmed/31958277 http://dx.doi.org/10.1136/rmdopen-2019-000995 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Sjögren Syndrome
Björk, Albin
Richardsdotter Andersson, Elina
Imgenberg-Kreuz, Juliana
Thorlacius, Gudny Ella
Mofors, Johannes
Syvänen, Ann-Christine
Kvarnström, Marika
Nordmark, Gunnel
Wahren-Herlenius, Marie
Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title_full Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title_fullStr Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title_full_unstemmed Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title_short Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sjögren’s syndrome
title_sort protein and dna methylation-based scores as surrogate markers for interferon system activation in patients with primary sjögren’s syndrome
topic Sjögren Syndrome
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046975/
https://www.ncbi.nlm.nih.gov/pubmed/31958277
http://dx.doi.org/10.1136/rmdopen-2019-000995
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