SPP1 and rheumatoid arthritis: Immunofluorescence staining of synovial biopsies from healthy controls and patients with active RA confirmed this finding at the spatial level: while healthy VSIG4pos lining layer STMs were SPP1-negative, macrophages in the hyperplastic lining of active RA patients were strongly SPP1-positive, establishing this TREM2low SPP1pos cluster as a defining feature of the pathogenic lining niche (Fig. 1F).