Psoriatic arthritis risk factors
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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:
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