Carvalho Ana L, Hedrich Christian M
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, United Kingdom.
Front Mol Biosci. 2021 Apr 1;8:662047. doi: 10.3389/fmolb.2021.662047. eCollection 2021.
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.
银屑病是一种主要影响皮肤的对称性自身免疫性/炎症性疾病。在相当一部分病例中，它伴有可累及任何关节、脊柱和/或包括附着点炎的关节炎。银屑病和银屑病关节炎是多因素疾病，其特征是在存在包括微生物群和/或表观遗传标记变化在内的其他（环境）因素的情况下，遗传易感个体出现异常免疫反应。表观遗传变化可以是可遗传的或后天获得的（例如，通过饮食/微生物群的变化或作为对治疗的反应），并且与遗传因素一起，促成疾病表现。在银屑病中，表观遗传改变主要与细胞增殖、细胞因子信号传导和微生物耐受性有关。了解导致银屑病发生和维持的遗传和后天发病机制因素之间的复杂相互作用，对于识别和验证诊断及预测生物标志物以及引入个性化的有效且可耐受的新治疗方法至关重要。本综述总结了目前对导致银屑病关节炎发病机制的免疫激活、遗传和环境因素的理解。特别关注这些因素之间的相互作用，以提出一种多因素疾病模型。
