Psoriatic arthritis risk factors
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD 
Genetic factors (eg, increased expression of HLA-B, HLA-C, single nucleotide polymorphisms involving various genes), immune mediators (eg, dendritic cells, T lymphocytes), and environmental agents(eg, infections, physical trauma) may act as a risk factors for the development of psoriatic arthritis.
- Genetic factors:
- Both psoriasis and psoriatic arthritis have been shown to have strong familial distribution among first degree relatives.
- psoriatic arthritis is frequently associated with HLA-B alleles than with HLA-C alleles, when compared to psoriasis.
- In patients with psoriatic arthritis when compared to general population, HLA antigens that are expressed more oftenly including HLA-B13, HLA-B17, HLA-B57, and HLA-Cw*0602.
- HLA CLASS 1 antigens that are related to psoriatic arthritis include HLA-B13, HLA-B38, HLA-B27, HLA-B39, and HLA-B57.
- HLA-B38 and HLA-B39 have a strong association with peripheral inflammatory articular disease, while HLA-B27 is strongly associated with spondylitis.
- HLA class 2 antigens that are associated with psoriatic arthritis including HLA-DRB1*04 and HLA-DRB1*07.
- HLA antigens, HLA-B27 along with HLA-DR7, HLA-DQ3 and in the absence of HLA-DR7, and HLA-B39 may be considered as predictors for disease progression. HLA-B22 antigen is protective for psoriatic arthritis.
- Increased risk for both psoriatic arthritis and psoriasis may be associated with following gene polymorphisms:
- TNF-alpha polymorphisms
- CARD15 gene on chrosome 16q: Pleiotropic autoimmune gene. It is the first non-MHC gene that can be associated with psoriatic arthritis.
- Polymorphisms involving IL-23 receptor and IL-12 beta genes.
- Interleukin 2 (IL2) and interleukin 21 (IL21)
- MHC class I chain-related gene A (MICA)
- IL-1 gene cluster polymorphism
- IL-13 polymorphism
- Increased risk for deveoping poriatic arthritis may also be related to interactions between certain HLA-class I alleles and killer inhibitory receptors (KIRs) located on chromosome 19. Psoriatic arthritis susceptibility is correlated with the presence of KIR2DS1 and/or KIR2DS2, and HLA-Cw alleles.
- Immune mechanisms:
- Presence of increased levels immunoglobulins and antinuclear antibodies in the serum may be found in patients with psoriatic arthritis.
- In patients with psoriatic arthritis, the synovial fluid contains reactive dendritic cells, which lead to activation of T lymphocytes by presenting an unknown antigen to CD4 positive T cells.
- Cytokines produced as a result of T cell activation and activation of other inflammatory precursors lead to proliferation and activation of synovial and epidermal fibroblasts.
- Excessively proliferated fibroblasts from epiderm and synovium may produce excess IL-1, IL-6, and platelet-derived growth factors.
- T lymphocytes may express HLA-DR and IL-2 receptor, and receptors to several adhesive molecules and cytokines particularly IL-6.
- Synovial fluid of patients with psoriatic arthritis will show increased levels of tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and IL-8.
- Elevated concentrations of serum interleukins including IL-10, IL-13, interferons particularly INF- alpha, chemokines such as CCL19, vascular endothelial growth factor, fibroblast growth factor, and decreased levels of granulocyte-colony stimulating factor may be found.
- Environmental factors:
- ↑ Nograles KE, Brasington RD, Bowcock AM (February 2009). "New insights into the pathogenesis and genetics of psoriatic arthritis". Nat Clin Pract Rheumatol. 5 (2): 83–91. doi:10.1038/ncprheum0987. PMC 2790861. PMID 19182814.
- ↑ Eder L, Chandran V, Pellet F, Shanmugarajah S, Rosen CF, Bull SB, Gladman DD (January 2012). "Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis". Ann. Rheum. Dis. 71 (1): 50–5. doi:10.1136/ard.2011.155044. PMID 21900282.
- ↑ Gladman DD, Cheung C, Ng CM, Wade JA (March 1999). "HLA-C locus alleles in patients with psoriatic arthritis (PsA)". Hum. Immunol. 60 (3): 259–61. PMID 10321964.
- ↑ Gladman DD, Farewell VT, Kopciuk KA, Cook RJ (April 1998). "HLA markers and progression in psoriatic arthritis". J. Rheumatol. 25 (4): 730–3. PMID 9558177.
- ↑ Rahman P, Siannis F, Butt C, Farewell V, Peddle L, Pellett F, Gladman D (July 2006). "TNFalpha polymorphisms and risk of psoriatic arthritis". Ann. Rheum. Dis. 65 (7): 919–23. doi:10.1136/ard.2005.039164. PMC 1798211. PMID 16284098.
- ↑ Rahman P, Bartlett S, Siannis F, Pellett FJ, Farewell VT, Peddle L, Schentag CT, Alderdice CA, Hamilton S, Khraishi M, Tobin Y, Hefferton D, Gladman DD (September 2003). "CARD15: a pleiotropic autoimmune gene that confers susceptibility to psoriatic arthritis". Am. J. Hum. Genet. 73 (3): 677–81. doi:10.1086/378076. PMC 1180694. PMID 12879366.
- ↑ Filer C, Ho P, Smith RL, Griffiths C, Young HS, Worthington J, Bruce IN, Barton A (December 2008). "Investigation of association of the IL12B and IL23R genes with psoriatic arthritis". Arthritis Rheum. 58 (12): 3705–9. doi:10.1002/art.24128. PMC 3001112. PMID 19035472.
- ↑ Gonzalez S, Martinez-Borra J, Torre-Alonso JC, Gonzalez-Roces S, Sanchez del Río J, Rodriguez Pérez A, Brautbar C, López-Larrea C (May 1999). "The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis". Arthritis Rheum. 42 (5): 1010–6. doi:10.1002/1529-0131(199905)42:5<1010::AID-ANR21>3.0.CO;2-H. PMID 10323458.
- ↑ Williams F, Meenagh A, Sleator C, Cook D, Fernandez-Vina M, Bowcock AM, Middleton D (July 2005). "Activating killer cell immunoglobulin-like receptor gene KIR2DS1 is associated with psoriatic arthritis". Hum. Immunol. 66 (7): 836–41. doi:10.1016/j.humimm.2005.04.005. PMID 16112031.
- ↑ Partsch G, Steiner G, Leeb BF, Dunky A, Bröll H, Smolen JS (March 1997). "Highly increased levels of tumor necrosis factor-alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid". J. Rheumatol. 24 (3): 518–23. PMID 9058659.
- ↑ Szodoray P, Alex P, Chappell-Woodward CM, Madland TM, Knowlton N, Dozmorov I, Zeher M, Jarvis JN, Nakken B, Brun JG, Centola M (March 2007). "Circulating cytokines in Norwegian patients with psoriatic arthritis determined by a multiplex cytokine array system". Rheumatology (Oxford). 46 (3): 417–25. doi:10.1093/rheumatology/kel306. PMID 16936328.
- ↑ Barnas JL, Ritchlin CT (November 2015). "Etiology and Pathogenesis of Psoriatic Arthritis". Rheum. Dis. Clin. North Am. 41 (4): 643–63. doi:10.1016/j.rdc.2015.07.006. PMID 26476224.
- ↑ Hsieh J, Kadavath S, Efthimiou P (May 2014). "Can traumatic injury trigger psoriatic arthritis? A review of the literature". Clin. Rheumatol. 33 (5): 601–8. doi:10.1007/s10067-013-2436-7. PMID 24249146.
- ↑ Thrastardottir T, Love TJ (November 2017). "Infections and the risk of psoriatic arthritis among psoriasis patients: a systematic review". Rheumatol. Int. doi:10.1007/s00296-017-3873-4. PMID 29124396.
- ↑ Arnett FC, Reveille JD, Duvic M (February 1991). "Psoriasis and psoriatic arthritis associated with human immunodeficiency virus infection". Rheum. Dis. Clin. North Am. 17 (1): 59–78. PMID 2041889.
- ↑ Njobvu P, McGill P (July 2000). "Psoriatic arthritis and human immunodeficiency virus infection in Zambia". J. Rheumatol. 27 (7): 1699–702. PMID 10914854.
- ↑ Eder L, Shanmugarajah S, Thavaneswaran A, Chandran V, Rosen CF, Cook RJ, Gladman DD (February 2012). "The association between smoking and the development of psoriatic arthritis among psoriasis patients". Ann. Rheum. Dis. 71 (2): 219–24. doi:10.1136/ard.2010.147793. PMID 21953342.