Transcription profiling of peripheral B cells in antibody-positive primary Sjögren's syndrome reveals upregulated expression of CX3CR1 and a type I and type II interferon signature.
Juliana Imgenberg-KreuzJ K SandlingA BjörkJ NordlundM KvarnströmM-L ElorantaL RönnblomMarie Wahren-HerleniusA-C SyvänenGunnel NordmarkPublished in: Scandinavian journal of immunology (2018)
B cells play a key role in the pathogenesis of primary Sjögren'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 α < 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.
Keyphrases
- gene expression
- poor prognosis
- genome wide
- dendritic cells
- single cell
- dna methylation
- genome wide identification
- binding protein
- immune response
- long non coding rna
- rheumatoid arthritis
- cell proliferation
- rna seq
- transcription factor
- bioinformatics analysis
- liver injury
- multiple sclerosis
- small molecule
- drug induced
- regulatory t cells
- systemic lupus erythematosus
- risk assessment
- current status
- climate change