Clinical implications of synovial tissue phenotypes in rheumatoid arthritis

Autoimmune forms of inflammatory arthritis, such as Rheumatoid Arthritis (RA), are clinically heterogeneous in presentation and disease course. Treatment-related outcomes vary despite patient exposure to similar treatment strategies. It is likely that variation seen in synovial pathogenesis influences outcomes and is heterogeneous outcomes influenced by patient factors, including environmental exposures, microbiota, behaviors, timely access to therapy, and synovial cell variation. Patients' unique complex factors manifest as specific synovial phenotypes characterized by clusters of synovial cell types and states. Precision medicine aims to use such clinical and biological data to identify the right treatment for the right patient at the right time, enabling patients to achieve sustained remission. Identifying synovial targets susceptible to a given treatment, enabling the choice of effective therapy for a given patient, will realize the goals of precision medicine. Over the last 7 years, improved acquisition and processing of synovial tissue obtained by ultra-sound guided biopsy has enabled researchers to define synovial pathotypes using histologic features and predominant cell types associated with clinical manifestations. Technical advances have enabled single-cell simultaneous sequencing of proteins and gene expression that, through increasingly sophisticated bioinformatics methods, have taken transcriptional and proteomic data to identify diverse and novel cell types and states that cluster in the RA synovium to further define patient subgroups. Synovial pathotypes and endotypes are now integrated into clinical studies and trials to explain clinical heterogeneity in disease course and treatment response. Rapidly evolving clinical-translational research has linked an expanded understanding of RA synovial pathogenesis with clinically meaningful subgroups and treatment outcomes and the clinical heterogeneity in RA.