Department of Orthopedic Surgery, New York University Medical Center, Hospital for Joint Diseases, New York, New York.
Department of Cell Biology, New York University School of Medicine, New York, New York.
Ann N Y Acad Sci. 2019 Apr;1442(1):5-16. doi: 10.1111/nyas.13933. Epub 2018 Jul 15.
Over the past two decades, considerable advances in our understanding of inflammatory and immune pathways have allowed for the growing use of targeted biologic therapy. Most notably, the introduction of tumor necrosis factor (TNF) inhibitors has dramatically changed the management of autoimmune inflammatory disorders, including ankylosing spondylitis (AS). Despite the efficacy of TNF inhibitors documented in multiple clinical trials, anti-TNF therapy in AS is far from foolproof; it is associated with serious adverse effects and limited response to therapy in some patients. Moreover, specific questions regarding the role of TNF as a mediator of AS remain unanswered. Therefore, additional efforts are needed in order to better understand the role of TNF in the pathogenesis of AS and to develop safer and more effective treatment strategies. The purpose of this review is to better the understanding of the physiologic and pathogenic roles of TNF signaling in the course of AS. Relevant TNF biology and novel approaches to TNF blockade in AS are discussed.
在过去的二十年中，我们对炎症和免疫途径的理解取得了相当大的进展，这使得靶向生物治疗的应用越来越广泛。值得注意的是，肿瘤坏死因子（TNF）抑制剂的引入极大地改变了自身免疫性炎症性疾病的治疗方法，包括强直性脊柱炎（AS）。尽管多项临床试验证明了 TNF 抑制剂的疗效，但 AS 中的抗 TNF 治疗远非万无一失；它与严重的不良反应有关，并且在一些患者中对治疗的反应有限。此外，关于 TNF 作为 AS 中介的具体问题仍未得到解答。因此，需要进一步努力，以便更好地了解 TNF 在 AS 发病机制中的作用，并开发更安全、更有效的治疗策略。本文旨在更好地理解 TNF 信号在 AS 病程中的生理和病理作用。讨论了相关的 TNF 生物学和 AS 中 TNF 阻断的新方法。
