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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
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- Imgenberg-Kreuz, Juliana (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär medicin,Reumatologi
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- Sandling, Johanna K. (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Reumatologi
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- Bjork, A. (författare)
- Karolinska Institutet
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- Nordlund, J. (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Kvarnstrom, M. (författare)
- Karolinska Institutet
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- Eloranta, Maija-Leena (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Rönnblom, Lars (författare)
- Uppsala universitet,Reumatologi,Science for Life Laboratory, SciLifeLab
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- Wahren-Herlenius, M. (författare)
- Karolinska Institutet
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- Syvänen, Ann-Christine, 1950- (författare)
- Uppsala universitet,Molekylär medicin,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)
- 2018-04-18
- 2018
- Engelska.
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 87:5
- Relaterad länk:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- 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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- ref (ämneskategori)
- art (ämneskategori)
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