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Transcription profiling of peripheral B cells in antibody-positive primary Sjogren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Karolinska Inst, Dept Med, Karolinska Univ Hosp, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2018 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 87, no 5, article id UNSP e12662Article in journal (Refereed) Published
Abstract [en]

B cells play a key role in the pathogenesis of primary Sjogren's syndrome (pSS). The aim of this study was to analyse the transcriptome of CD19+ B cells from patients with pSS and healthy controls to decipher the B cell-specific contribution to pSS. RNA from purified CD19+ B cells from 12 anti-SSA antibody-positive untreated female patients with pSS and 20 healthy blood donors was subjected to whole transcriptome sequencing. A false discovery rate corrected significance threshold of <0.05 was applied to define differential gene expression. As validation, gene expression in B cells from 17 patients with pSS and 16 healthy controls was analysed using a targeted gene panel. RNA-sequencing identified 4047 differentially expressed autosomal genes in pSS B cells. Upregulated expression of type I and type II interferon (IFN)-induced genes was observed, establishing an IFN signature in pSS B cells. Among the top upregulated and validated genes were CX3CR1, encoding the fractalkine receptor involved in regulation of B-cell malignancies, CCL5/RANTES and CCR1. Increased expression of several members of the TNF superfamily was also identified; TNFSF4/Ox40L, TNFSF10/TRAIL, TNFSF13B/BAFF, TNFRSF17/BCMA as well as S100A8 and -A9/calprotectin, TLR7, STAT1 and STAT2. Among genes with downregulated expression in pSS B cells were SOCS1 and SOCS3, CD70 and TNFAIP3/A20. We conclude that B cells from patients with anti-SSA antibody-positive pSS display immune activation with upregulated expression of chemokines, chemokine receptors and a prominent type I and type II IFN signature, while suppressors of cytokine signalling are downregulated. This adds insight into the autoimmune process and suggests potential targets for future functional studies.

Place, publisher, year, edition, pages
2018. Vol. 87, no 5, article id UNSP e12662
National Category
Immunology in the medical area Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-354096DOI: 10.1111/sji.12662ISI: 000430398400006PubMedID: 29655283OAI: oai:DiVA.org:uu-354096DiVA, id: diva2:1220942
Funder
Knut and Alice Wallenberg Foundation, 2011.0073Swedish Research Council, 2012-2148Swedish Research Council, 350-2012-256Swedish Research Council, 521-2013-2830Swedish Research Council, 521-2014-2263Swedish Research Council, 2016-01982Knut and Alice Wallenberg FoundationSwedish Research CouncilAvailable from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved

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Imgenberg-Kreuz, JulianaSandling, Johanna K.Eloranta, Maija-LeenaRönnblom, LarsSyvänen, Ann-ChristineNordmark, Gunnel
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