Molecular and cellular heterogeneity in the Rheumatoid Arthritis synovium: Clinical correlates of synovitis

Abstract Rheumatoid Arthritis is characterized by autoimmune-mediated attack of the joint synovial lining resulting in destruction of bone and cartilage, and is a clinically and biologically heterogenous disease with respect to both course of disease and outcome to therapy. The current armamentarium of approved therapies does not result in complete clinical response in all patients. Improved techniques for imaging and performing biopsies on the rheumatoid synovium have facilitated multiple studies of the dysregulated cellular and molecular pathways in disease, and have provided evidence for a spectrum of pathogenic phenotypes across RA patients. These phenotypes are differentially affected by targeted therapies such as anti-TNFα and anti-CD20, and their presence prior to treatment impacts upon subsequent clinical outcomes. Ongoing histologic and molecular assessment of these synovial phenotypes through the implementation of routine synovial biopsy or using systemic biomarkers will improve targeting of therapies to specific patient subsets in both clinical trials and practice.