Schett Georg, Rahman Proton, Ritchlin Christopher, McInnes Iain B, Elewaut Dirk, Scher Jose U
Department of Medicine 3, Friedrich Alexander University Erlangen-Nuremberg and Universitaets-klinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum Immuntherapie DZI, Friedrich Alexander University Erlangen-Nuremberg and Universitaets-klinikum Erlangen, Erlangen, Germany.
Nat Rev Rheumatol. 2022 Jun;18(6):311-325. doi: 10.1038/s41584-022-00776-6. Epub 2022 May 5.
Psoriatic arthritis (PsA) is part of a group of closely related clinical phenotypes ('psoriatic disease') that is defined by shared molecular pathogenesis resulting in excessive, prolonged inflammation in the various tissues affected, such as the skin, the entheses or the joints. Psoriatic disease comprises a set of specific drivers that promote an aberrant immune response and the consequent development of chronic disease that necessitates therapeutic intervention. These drivers include genetic, biomechanical, metabolic and microbial factors that facilitate a robust and continuous mobilization, trafficking and homing of immune cells into the target tissues. The role of genetic variants involved in the immune response, the contribution of mechanical factors triggering an exaggerated inflammatory response (mechanoinflammation), the impact of adipose tissue and altered lipid metabolism and the influence of intestinal dysbiosis in the disease process are discussed. Furthermore, the role of key cytokines, such as IL-23, IL-17 and TNF, in orchestrating the various phases of the inflammatory disease process and as therapeutic targets in PsA is reviewed. Finally, the nature and the mechanisms of inflammatory tissue responses inherent to PsA are summarized.
银屑病关节炎（PsA）是一组密切相关的临床表型（“银屑病性疾病”）的一部分，该组疾病由共同的分子发病机制定义，导致在受影响的各种组织（如皮肤、肌腱附着点或关节）中出现过度、持续的炎症。银屑病性疾病包括一组特定的驱动因素，这些因素会促进异常免疫反应以及随之而来的需要进行治疗干预的慢性疾病的发展。这些驱动因素包括遗传、生物力学、代谢和微生物因素，它们有助于免疫细胞强有力且持续地动员、运输并归巢至靶组织。本文讨论了参与免疫反应的基因变异的作用、引发过度炎症反应（机械性炎症）的机械因素的作用、脂肪组织和脂质代谢改变的影响以及肠道生态失调在疾病过程中的影响。此外，还综述了关键细胞因子（如IL-23、IL-17和TNF）在协调炎症性疾病过程的各个阶段以及作为PsA治疗靶点方面的作用。最后，总结了PsA固有炎症组织反应的性质和机制。
