Secretory phenotype in PBMCs of elderly patients with rheumatoid arthritis
Purpose: The senescence-associated secretory phenotype (SASPs) might increase risk of age-related diseases and concomitant diseases in elderly rheumatoid arthritis (ERA) patients. This study aims to investigate the SASPs in peripheral blood mononuclear cells (PBMCs) for ERA patients. Methods: We performed RNA-seq of the PBMCs from 5 aged RA (RA_A) and 4 young RA (RA_Y) patients. By comparing the differentially expressed genes (DEGs) of RA_Y and RA_A using DESeq package, we identified the senescent secretory phenotype of ERA. The Gene Ontology (GO) functional enrichment, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and GSEA analysis were performed using clusterProfiler package. The significant protein–protein interaction (PPI) networks identified by Cytoscape. The proteomics data that investigate secretory phenotype of ERA was download from proteomics database. The overlapping SASPs at the intersection of proteomic and transcriptomic were then validated using real-time PCR (RT-PCR).  Results: The PBMCs of RA_A and RA_Y had heterogeneity transcriptomic feature. By comparing RA_A with RA_Y groups, 348 up-regulated and 363 down-regulated DEGs were identified. Gene functional enrichment indicated that up-regulated DEGs in RA_A, SASPs for ERA patients, enriched in PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor family, neutrophil degranulation and immune-related pathways and so on. GSEA analysis indicated, humoral immune response pathways were activated in RA_A. By performing RT-PCR, these five SASPs, SPTA1, SPTB, VNN1, TNXB, KRT1, in PBMCs of RA patients were finally validated. Conclusion: Our study revealed the aging phenotypes in PBMCs of RA patients, and validated five SASPs, which providing novel insights for targeting SASPs therapy. Overall design: We performed RNA-seq on peripheral blood mononuclear cells (PBMCs) from aged RA patients (RA_A) and young RA patients (RA_Y). By comparing the differentially expressed genes (DEGs) between RA_A and RA_Y, the SASPs in PBMCs of ERA patients was revealed and validated by performing RT-PCR.