Age-related genes USP2 and ARG2 are involved in the reduction of immune cell infiltration in elderly patients with rheumatoid arthritis.

Abstract

There are large differences in clinical manifestations and biological markers between elderly patients with rheumatoid arthritis (EPRA, age >60) and younger patients with RA (YPRA, age ≤60), partly owing to variations in the immune system of different age groups. Here, we focused on the changes of immune cell infiltration in YPRA and EPRA. The R packages "ssGSEA" and "GSEA" were used to identify the changes in immune cell infiltration and immune-related pathways between the two groups. The R packages "WGCNA" and "DEseq2" were used to screen and verify age-related differentially expressed genes (DEGs). Hub genes were identified using Cytoscape and cytoHubba. Spearman correlation coefficient was conducted to evaluate correlations between hub age-related genes and immune cells. Compared with 54 established YPRA, several immune cells and immune-related pathways were markedly decreased in 29 EPRA synovial tissues. Moreover, 78 age-related DEGs related to amino acid and glycosphingolipid synthesis and metabolism were identified. USP2 and ARG2 were verified to be upregulated in EPRA, signifying that these two genes could effectively distinguish YPRA and EPRA and have potential as biomarkers. In addition, we found that USP2 was significantly negatively correlated with B cells and monocytes, while there was a significant negative association between ARG2 and T cells. In conclusion, this study is the first to systematically analyze changes in immune cell infiltration between YPRA and EPRA patients and obtain hub age-related genes, which may provide the basis for illuminating the pathogenesis of EPRA and informing treatment strategies.