Cellular and molecular diversity in Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects synovial joints, with inflammation of the synovial membrane (synovitis), characterised by neo-angiogenesis, hyperplasia of lining layer, and immune cell infiltration that drive local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous, both at cellular and molecular level, which can at least in part explain why despite the availability of highly effective treatment options, a large proportion of patients are resistant to some individual treatments. The assimilation of recent high-throughput data from analysis at the single-cell level with rigorous and high-quality clinical outcomes obtained from large randomised clinical trials support the definition of disease and treatment response endotypes. Looking ahead, the integration of histological and molecular signatures from the diseased tissue into clinical algorithms may help decision making in the management of patients with Rheumatoid Arthritis in clinical practice.