Similarities and differences between osteoarthritis and rheumatoid arthritis: insights from Mendelian randomization and transcriptome analysis

Osteoarthritis and rheumatoid arthritis are often difficult to distinguish at an early stage of the disease.

The authors first performed a correlation analysis of phenotypic data from genome-wide association studies, arthrosis and rheumatoid arthritis. They then proceeded to the functional enrichment and pathways of genes differentially expressed in patients with osteoarthritis, rheumatoid arthritis and in normal patients. The infiltration of immune cells into arthritis was analyzed according to gene expression.

Finally, the Mendelian randomization analysis was performed with inflammatory cytokines and immune cells as exposure, and arthritis as result. Both methods of analysis resulted in identical or different key cytokines and immune cells.

The pan-genomic association study showed that there was a genetic correlation between osteoarthritis and rheumatoid arthritis. T cells are the main immune cells that differentiate osteoarthritis from rheumatoid arthritis.

The Mendelian randomization analysis also revealed that osteoarthritis is associated with more protective cytokines, while most of the cytokines in rheumatoid arthritis are pathogenic. In addition, the CCR7 receptor on naïve CD4+ T cells was positively correlated with osteoarthritis. SSC-A on CD4+ T cells was negatively correlated to rheumatoid arthritis, while HLA DR on CD33- HLA DR+ cells was positively correlated to rheumatoid arthritis.