Autoimmune rheumatologic diseases
Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are considered related autoimmune diseases that share similar genetic variants and lymphocyte infiltration. Recently, single-cell technologies have provided an opportunity to understand cellular heterogeneity by querying damaged tissue. Across diseases, similarities in autoimmune and inflammatory cell states at the single-cell level in human tissues are currently understudied. To this end, we applied an integrative pipeline to harmonize 5,265 RA synovial cells and 6,857 lupus kidney cells from parallel single cell RNA-seq data generated by the Accelerated Medicines Partnership (AMP) RA/SLE consortium1,2,3,4. We observed multiple shared major cell types including T cells, B cells, myeloid cells, and fibroblasts. We analyzed each identified cell type across diseases and observed multiple shared subpopulations, including inflammatory and tissue resident macrophages, Tph and Treg CD4+ cells, GzmB+ and GzmK+ T cells, naïve and activated B cells. Across shared Tph cells, we observed an upregulation in type I interferon signaling (FDR p=1e-5) among SLE Tph cells, while RA Tph cells showed upregulation in cyclic adenosine monophosphate (FDR p=1e-4). Integrative analyses between damaged tissue from RA and SLE by single-cell transcriptomics focusing on shared cellular populations has identified shared and disease-specific gene expression modules, and should help predict potential therapeutics for RA and SLE in the future.