Psoriatic arthritis risk factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]

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:^[1][2][3]
  • 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.^[4]
  • Increased risk for both psoriatic arthritis and psoriasis may be associated with following gene polymorphisms:
    • TNF-alpha polymorphisms^[5]
    • CARD15 gene on chrosome 16q: Pleiotropic autoimmune gene. It is the first non-MHC gene that can be associated with psoriatic arthritis.^[6]
    • Polymorphisms involving IL-23 receptor and IL-12 beta genes.^[7]
    • Interleukin 2 (IL2) and interleukin 21 (IL21)
    • MHC class I chain-related gene A (MICA)^[8]
    • 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.^[9]
• Immune mechanisms:^[10][11][12]
  • 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:
  • Trauma: Koebner’s phenomenon^[13]
  • Infections:^[14][15]
    • Bacterial (eg, streptococcus)
    • Viral (eg, HIV)^[16]
  • Smoking: May have inverse relation with psoriatic arthritis among psoriasis patients.^[17]

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