Abstract
BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. METHODS: We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. RESULTS: GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. CONCLUSION: Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.