Evolving concepts of rheumatoid arthritis

Abstract

Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Early theories on the pathogenesis of rheumatoid arthritis focused on autoantibodies and immune complexes. T-cell-mediated antigen-specific responses, T-cell-independent cytokine networks, and aggressive tumour-like behaviour of rheumatoid synovium have also been implicated. More recently, the contribution of autoantibodies has returned to the forefront. Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.

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Figure 1: Synovial histology in rheumatoid arthritis.
Figure 2: Cytokine networks in rheumatoid arthritis.
Figure 3: A proposed model implicating multiple pathogenic mechanisms in RA.

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Acknowledgements

Supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The author also thanks N. J. Zvaifler for helpful discussions on this topic as well as two decades of instruction, collaboration and friendship.

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Correspondence to Gary S. Firestein.

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Firestein, G. Evolving concepts of rheumatoid arthritis. Nature 423, 356–361 (2003). https://doi.org/10.1038/nature01661

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