A comprehensive gene expression meta-analysis identifies novel immune signatures in rheumatoid arthritis patients

dc.contributor.author Afroz, Sumbul
dc.contributor.author Giddaluru, Jeevan
dc.contributor.author Vishwakarma, Sandeep
dc.contributor.author Naz, Saima
dc.contributor.author Khan, Aleem Ahmed
dc.contributor.author Khan, Nooruddin
dc.date.accessioned 2022-03-27T01:03:52Z
dc.date.available 2022-03-27T01:03:52Z
dc.date.issued 2017-02-02
dc.description.abstract Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.
dc.identifier.citation Frontiers in Immunology. v.8(FEB)
dc.identifier.uri 10.3389/fimmu.2017.00074
dc.identifier.uri http://journal.frontiersin.org/article/10.3389/fimmu.2017.00074/full
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/4044
dc.subject Autoimmunity
dc.subject Meta-analysis
dc.subject Microarrays
dc.subject Rheumatoid arthritis
dc.subject Synovial inflammation
dc.title A comprehensive gene expression meta-analysis identifies novel immune signatures in rheumatoid arthritis patients
dc.type Journal. Article
dspace.entity.type
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