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New insights into the pathogenesis and genetics of psoriatic arthritis

Abstract

Psoriasis vulgaris and psoriatic arthritis (PsA) are inter-related heritable diseases. Psoriatic skin is characterized by hyperproliferative, poorly differentiated keratinocytes and severe inflammation. Psoriatic joints are characterized by highly inflamed synovia and entheses with focal erosions of cartilage and bone. Genetic analyses have uncovered risk factors shared by both psoriasis and PsA. Predisposition to psoriasis and PsA arising from common variation is most strongly conferred by the HLA class I region. Other genetic risk factors implicate the interleukin (IL)-23 pathway and the induction and regulation of type 17 T-helper cells in the pathogenesis of both diseases. Secretion of cytokines, such as IL-22 and IL-17, could result in the hyperproliferative phenotype of keratinocytes and potentially synoviocytes, leading to a vicious cycle of cellular proliferation and inflammation in both the skin and joints. In synovial tissue, disease-related cytokines could also promote osteoclast formation, resulting in bone erosion. The next step will be to identify genetic risk factors specifically associated with PsA. Although therapies that target tumor necrosis factor are often highly successful in the treatment of both diseases, genetic findings are likely to lead to the development of treatments tailored to an individual's genetic profile.

Key Points

  • Multiple genes with low risk effects are involved in susceptibility to psoriasis vulgaris and psoriatic arthritis (PsA)

  • Newly uncovered genetic associations shared by psoriasis and PsA implicate components of the IL-23–TH17 pathway in both diseases

  • Given these genetic links, further evaluation of the pathogenic role of the IL-23–TH17 pathway in PsA is warranted

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Figure 1: Model of the relationship between skin and joint inflammation associated with psoriasis vulgaris and psoriatic arthritis.

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Acknowledgements

Supported in part by an NIH grant (AMB) and the Clinical Scholars Program at The Rockefeller University (KEN). We thank Drs James Krueger and Michelle Lowes for critical comments on the Review.

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Correspondence to Anne M Bowcock.

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RD Brasington has received research support from Abbott, Centocor and Wyeth, and speakers' honoraria from Abbott and Centocor for work in relation to therapeutics for rheumatoid arthritis. The other authors declared no competing interests.

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Nograles, K., Brasington, R. & Bowcock, A. New insights into the pathogenesis and genetics of psoriatic arthritis. Nat Rev Rheumatol 5, 83–91 (2009). https://doi.org/10.1038/ncprheum0987

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