Landscape of Gene Mutation in Synovium of Patients with Rheumatoid Arthritis

Objective To investigate accumulating single nucleotide variants (SNVs) in synovium of patients with early, pre-treatment rheumatoid arthritis (RA). Methods I leveraged RNA-seq dataset derived from patients with RA deposited in database. To capture synovium-specific mutations, I applied standardized SNVs-calling method to paired synovium and blood samples per individual. Results De novo mutational signatures constructed by non-negative matrix factorization reflected continuous relationship of synovial histology, namely lymphoid-myeloid (Lymphoid), diffuse myeloid (Myeloid) and pauci-immune fibroid (Fibroid). Using COSMIC signature, defective DNA damage repair-associated mutational signature was associated with the level of inflammation in synovitis. Further, pathway analysis based on specific genes harboring SNVs in each histological group represent different types of synovitis, with differing pathogenic process and inflammatory environment. Conclusion This data will promote our understandings about pathogenic status of synovitis, and suggests evidence that stratified treatments would be optimal according to histological subgroup.