P071/O13 RNA sequencing detection of gene dysregulation in B cells sorted from salivary gland tissue and from peripheral blood reveals new pathways involved in primary sjÖgren's syndrome pathophysiology. (March 2019)

• Record Type: Journal Article
• Authors: Rivière, E; Tchitchek, N; Nocturne, G; Pascaud, J; Boudaoud, S; Thai, A; Allaire, N; Jagla, B; Mingueneau, M; Mariette, X
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A30
• Page End: A30
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.60
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Student for a master or a PhD. Introduction: Primary Sjögren's syndrome (pSS) is a chronic auto-immune disorder characterized by lymphocytic infiltrates and destruction of the salivary glands (SG). Chronic B cell activation, the secretion of autoantibodies and the critical role of BAFF have been demonstrated. However, mechanisms leading to B cells dysregulation remain partially understood. Objectives: To establish transcriptomic maps of the B cells sorted from the SG and from blood in pSS patients and controls using RNASeq. Methods: Patients had pSS according to 2016 EULAR/ACR criteria and controls had sicca symptoms without any antibodies and with normal SG biopsy. B cells were sorted from SG biopsies and from blood using a FACS ARIA. RNASeq profiling was performed using MiSeq. Statistical analysis identified differentially expressed genes between pSS and controls in B cells sorted from SG (9 pSS, 4 controls), from blood (16 pSS, 7 controls); and between B cells sorted from SG and blood in the same patients (4 pSS patients). Functional enrichment analysis used Ingenuity Pathway Analysis. Results: The pSS vs controls comparison in B cells sorted from SG identified up-regulated genes involved in activation of B cells including CD48, CD22 and CD40. TLR10, which is involved in innate immunity was also up-regulated in pSS. In blood B cells, TLR7 and the downstream signaling molecule IRF7 were up-regulated in pSS. Additionally, IL-6 which is involved in B cells growth was up-regulated. Enrichment analysis highlighted EIF2 signaling pathway, interferon (IFN) signaling pathway and role of JAK in IFN signaling. The paired comparison between B cells from SG and from blood identified up-regulated genes including CD138, a plasma cell marker, IL-6, TLR5 and IFN induced genes. The confirmation by qPCR of these results is ongoing. Conclusions: This study allowed to explore the mechanisms that support B cell activation in pSS focusing on tissue resident and circulating cells. Data confirmed B cell activation and differentiation through several markers and highlighted the role of innate immunity and key pathways including IFN and JAK signaling. Precise understanding of these dysregulations should offer development of new targeted therapeutic perspectives. Disclosure of Interest: None declared.