Rheumatic & Musculoskeletal Diseases Research

Recent advances in pre-clinical and clinical research into the Rheumatic Diseases have fundamentally changed the practice of Rheumatology and the prognosis of patients with Rheumatic disease. The development of TNF blockade as a novel and highly effective treatment for RA, psoriatic arthritis, ankylosing spondylitis and inflammatory bowel disease is one of the most exciting discoveries in 20th century medicine. This achievement was made possible by pre-clinical research that identified TNF alpha as a key player in the pathogenesis of inflammatory arthritis in both rodent models and human disease. These basic discoveries were made possible by fundamental advances in the areas of immunology, molecular biology and genetics. Thus, this major clinical advance is the fruit of a coordinated effort involving basic, disease-focused, and clinical research. Indeed, this discovery is a testament to the power of collaborative interactions between pre-clinical scientists, clinical scientists and clinicians.

It is clear that TNF blockade is the tip of a therapeutic iceberg. IL-1b blockade is approved for the treatment of RA and IL-6 blockade is undergoing clinical trials. Monoclonal antibodies directed at the B cell antigen CD20 have recently been approved for the treatment of RA. Antibodies that target cell surface integrins to inhibit the recruitment of inflammatory mononuclear cells to sites of inflammation have been shown to ameliorate inflammatory arthritis. Gene array studies have identified an “interferon signature” within peripheral blood cells from patients with lupus, a finding that identifies interferon as a potential drug target for the treatment of this autoimmune disease. These exciting discoveries have changed the way we think about the pathogenesis and treatment of immune mediated inflammatory disease.

Research in this area is encompassed by three major programs: a) Cellular and molecular effectors of arthritis, b) Animal models of rheumatic disease, and c) Genetics of rheumatic disease, and fosters collaboration and interactions between investigators within the Division. The research involves the use if an animal model of inflammatory arthritis developed by Drs. Diane Mathis and Christophe Benoist to identify key cellular, molecular, and genetic features of this disease.