AB0148 ANALYSIS OF DIFFERENTIALLY EXPRESSED GENES AND MICRORNAS OF B CELLS IN PRIMARY SJOGREN’S SYNDROME BY RNA SEQUENCING

Abstract

Background:Primary Sjogren’s syndrome (pSS) is a chronic autimmune disease mainly characterized by the inflammation of exocrine glands. There two key insights into pSS pathogenesis, which included “IFN signature” and hyperactivity of B cells. mRNA and microRNA (miRNA) are very important to control the gene expression.Objectives:In this research, we analyzed the differentially expressed genes (DEG) and miRNA of B cells in pSS patients by RNA-sequencing. And we aim to preliminarily screen out some special miRNAs and target gene loci that may be involved in transcription regulation of B cells of pSS.Methods:Peripheral blood samples from 3 pSS patients and 3 age-matched healthy controls (HC) were collected. CD19+B cells were sorted by Magnetic cell sorting method. Total RNA was extracted and cDNA of transcriptome or miRNA analysis were prepared and RNA-sequencing was performed to screen the DEG and miRNA. The GO Terms was used to uncover the biological function of DEGs, and the KEGG pathway enrichment was used to find out the related signal pathway. The mRNA-miRNA conjoint analysis was also performed.Results:There were a total of 73 significantly DEGs in B cells of pSS patients compared to HC, including 51 upregulated DEGs (such asIFI44L,IFI44,IFIT1,IFITM1,IFIT3,IFIT2,IRF7,IFI6andISG15)and 22 downregulated DEGs (such asESR2andEGR1). GO Terms and KEGG pathway analyses showed that most of the upregulated DEGs were enriched in IFN signaling and IFN regulatory pathway, and also showed the relationship with microbial infection, such as influenza A virus, hepatitis C virus, measles and herpes simplex virus.There were five significantly differentially expressed miRNAs, including hsa-miR-4485-3p, hsa-miR-144-5p, hsa-miR-144-3p, hsa-miR-451a, hsa-miR-4732-3p. GO Terms and KEGG pathway analyses showed that most of the target genes which regulated by those miRNAs were enrichment on herpes simplex virus and TGF-β signaling pathway.DEG and differentially expressed miRNAs conjoint analysis showed that the target DEGs which regulated by those miRNAs participated in cytoskeleton formation and modification of DNA or RNA, such asRASD2,CKAP4,SPARS2L METTL.Conclusion:There were 51 upregulated DEGs and 22 downregulated DEGs in B cells of pSS patients. GO Terms and KEGG pathway analyses showed that most of the upregulated DEGs were enriched in IFN related signaling pathway, and also showed the significant relationship with microbial infection.Conjoint analysis showed that the target DEGs which regulated by differentially expressed miRNAs participated in cytoskeleton formation and modification of DNA or RNA. There maybe more than one regulatory methods lead to DEGs in B cells of pSS patients.Disclosure of Interests:None declared