Ciobanu Dana Alexandra, Poenariu Ioan Sabin, Crînguș Laura-Ioana, Vreju Florentin Ananu, Turcu-Stiolica Adina, Tica Andrei Adrian, Padureanu Vlad, Dumitrascu Roxana Mihaela, Banicioiu-Covei Simona, Dinescu Stefan Cristian, Boldeanu Lidia, Siloși Isabela, Ungureanu Anca Marilena, Boldeanu Mihail Virgil, Osiac Eugen, Barbulescu Andreea Lili
Department of Rheumatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Department of Immunology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Exp Ther Med. 2020 Oct;20(4):3498-3503. doi: 10.3892/etm.2020.8982. Epub 2020 Jul 9.
Rheumatoid arthritis (RA) is classified as an inflammatory, chronic autoimmune and disabling disease based on the intricate interplay between environmental and genetic factors. With a prevalence ranging from 0.3 to 1%, RA is the most prevalent inflammatory joint disease observed in adults. Disruption of immune tolerance becomes evident when abnormal stimulation of the innate and adaptive immune system occurs. This cascade of events causes persistent joint inflammation, proliferative synovitis and, ultimately, damage of the underlying cartilage as well as the subchondral bone, leading to permanent joint destruction, deformity and subsequent loss of function. With cytokines being the key to a multitude of biological processes, including inflammation, hematopoiesis and overall immune response, one must inevitably look at the main pathways through which a significant number of those molecules exert their function. Janus kinase/signal transducers and activators of transcription (JAK/STATs) represent one such pathway and, recently, JAK inhibitors (JAKinibs) have shown promise in the treatment of several inflammatory diseases, including RA. This narrative review focuses on the intricate signaling pathways involved as well as on the clinical aspects and safety profiles of JAKinibs approved for the treatment of RA.
类风湿性关节炎（RA）基于环境因素与遗传因素之间复杂的相互作用，被归类为一种炎症性、慢性自身免疫性致残疾病。RA的患病率在0.3%至1%之间，是成人中最常见的炎症性关节疾病。当先天性和适应性免疫系统受到异常刺激时，免疫耐受的破坏就会变得明显。这一系列事件会导致持续性关节炎症、增殖性滑膜炎，并最终导致深层软骨以及软骨下骨受损，从而导致永久性关节破坏、畸形以及随后的功能丧失。细胞因子是众多生物学过程（包括炎症、造血和整体免疫反应）的关键因素，因此人们必然要关注大量此类分子发挥其功能的主要途径。Janus激酶/信号转导子和转录激活子（JAK/STATs）代表了这样一种途径，最近，JAK抑制剂（JAKinibs）在治疗包括RA在内的几种炎症性疾病方面显示出了前景。这篇叙述性综述重点关注了相关的复杂信号通路以及已获批用于治疗RA的JAKinibs的临床方面和安全性概况。
