Next-Generation Sequencing Profiles of the Methylome and Transcriptome in Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis

Abstract

Using next-generation sequencing to decipher methylome and transcriptome and underlying molecular mechanisms contributing to rheumatoid arthritis (RA) for improving future therapies, we performed methyl-seq and RNA-seq on peripheral blood mononuclear cells (PBMCs) from RA subjects and normal donors. Principal component analysis and hierarchical clustering revealed distinct methylation signatures in RA with methylation aberrations noted across chromosomes. Methylation alterations varied with CpG features and genic characteristics. Typically, CpG islands and CpG shores were hypermethylated and displayed the greatest methylation variance. Promoters were hypermethylated and enhancers/gene bodies were hypomethylated, with methylation variance associated with expression variance. RA genetically associated genes preferentially displayed differential methylation and differential expression or interacted with differentially methylated and differentially expressed genes. These differentially methylated and differentially expressed genes were enriched with several signaling pathways and disease categories. 10 genes (CD86, RAB20, XAF1, FOLR3, LTBR, KCNH8, DOK7, PDGFA, PITPNM2, CELSR1) with concomitantly differential methylation in enhancers/promoters/gene bodies and differential expression in B cells were validated. This integrated analysis of methylome and transcriptome identified novel epigenetic signatures associated with RA and highlighted the interaction between genetics and epigenetics in RA. These findings help our understanding of the pathogenesis of RA and advance epigenetic studies in regards to the disease.

Expression and regulatory characteristics of peripheral blood immune cells in primary Sjögren’s syndrome patients using single-cell transcriptomic

“…In addition, FOLR3 and IL1B were upregulated in CD14 + Mos of different patients. FOLR3 is involved in rheumatoid arthritis ( Tseng et al., 2019 ) and SARS-CoV-2 ( Sfikakis et al., 2021 ), but its relationship with pSS has not been reported. According to data from this study, it was found that FOLR3 showed the opposite trend of IL1B expression.…”

Identification of DNA methylation-regulated differentially expressed genes in RA by integrated analysis of DNA methylation and RNA-Seq data

“…Huo et al [ 22 ] determined that abnormal methylation of CDC20 and CCNA2 may be effective in predicting the prognosis of RA with microarray combined with bioinformatics analysis. For RA, some studies combing microarray with bioinformatics analysis have revealed differential methylation signals at S100A6 and EFCAB4B promoter regions in the whole blood [ 23 ], CD86, RAB20, XAF1, FOLR3, LTBR, KCNH8, DOK7, PDGFA, PITPNM2, and CELSR1 in B cells [ 24 ], and IFN related genes (IFIT1, IRF7, MX1, OAS1, USP18, RSAD2, IFI44L) in CD4+ T cells [ 25 ]. However, until now, the methylation of RA-related genes are still insufficient.…”

Revealing Potential Spinal Cord Injury Biomarkers and Immune Cell Infiltration Characteristics in Mice

“…Rab20 up-regulation may contribute to plaque destabilization via increased autophagy and cell death ( Cederstrom et al, 2020 ). High Rab20 levels promote B cell activation and facilitate rheumatoid arthritis development ( Tseng et al, 2019 ). Rab20’s expression was increased during B cell transformation by a polymorphism associated with Crohn’s disease and vaccination ( Mehta et al, 2017 ).…”