Developments in the scientific understanding of rheumatoid arthritis |
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Authors: | Jörg J Goronzy Cornelia M Weyand |
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Institution: | 1. Lowance Center for Human Immunology and Rheumatology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
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Abstract: | Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually
leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel
insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive
T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of
the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations
and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens
can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions
in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced
activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting
mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome. |
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