Because recent studies using single-cell RNA-seq (scRNA-seq) on RA synovium identified specific fibroblast subsets with critical roles in RA pathogenesis13,14,16,29, we applied modular analysis based on scRNA-seq fibroblast subsets14 and orthogonal validation by multiplex immunofluorescence, and identified an association between DKK3+ fibroblasts and refractoriness. This evidence concerns the gene DKK3 and rheumatoid arthritis.