Abstract
Psoriasis is a symmetric autoimmune/inflammatory disease that primarily affects the skin. In a significant proportion of cases, it is accompanied by arthritis that can affect any joint, the spine, and/or include enthesitis. Psoriasis and psoriatic arthritis are multifactor disorders characterized by aberrant immune responses in genetically susceptible individuals in the presence of additional (environmental) factors, including changes in microbiota and/or epigenetic marks. Epigenetic changes can be heritable or acquired (e.g., through changes in diet/microbiota or as a response to therapeutics) and, together with genetic factors, contribute to disease expression. In psoriasis, epigenetic alterations are mainly related to cell proliferation, cytokine signaling and microbial tolerance. Understanding the complex interplay between heritable and acquired pathomechanistic factors contributing to the development and maintenance of psoriasis is crucial for the identification and validation of diagnostic and predictive biomarkers, and the introduction of individualized effective and tolerable new treatments. This review summarizes the current understanding of immune activation, genetic, and environmental factors that contribute to the pathogenesis of psoriatic arthritis. Particular focus is on the interactions between these factors to propose a multifactorial disease model.
Highlights
Psoriasis is a systemic autoimmune/inflammatory disorder that primarily affects the skin
Inflammation in psoriatic arthritis (PsA) is characterized by a global hypomethylation that is reversed by treatment with Methotrexate
Significant differences were found in IRAK1 rs3027898 polymorphism distribution between patients with PsA when compared with HC
Summary
Psoriasis is a systemic autoimmune/inflammatory disorder that primarily affects the skin. CD3+ TCR+ CD4− CD8− (“double negative”) T cells that can arise from CD8+ T cells are infiltrating the skin of psoriasis patients and produce the effector cytokine IFN-γ, likely contributing to aforementioned inflammatory cascades (Brandt et al, 2017) Their involvement in joint inflammation has not been investigated yet. Dendritic cells are a critical link between the innate and adaptive immune system They have been associated with various autoimmune/inflammatory diseases, including psoriasis, PsA, SLE, and others (Jongbloed et al, 2006; Hedrich, 2016; Xiao et al, 2020). Most genetic variants associated with skin disease are affecting immune inflammatory responses, differentiation of structural components of tissues such as angiogenesis, bone metabolism, and microbial tolerance (Cafaro and Mcinnes, 2018; Veale and Fearon, 2018; O’Rielly et al, 2019).
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