Cafaro G, Alunno A, Valentini V, Leone M C, Marcucci E, Bartoloni E, Gerli R
Rheumatology Unit, Department of Medicine, University of Perugia.
Reumatismo. 2016 Dec 31;68(4):167-175. doi: 10.4081/reumatismo.2016.892.
The etiopathogenesis of rheumatoid arthritis (RA) is not yet fully elucidated and the site of inflammation onset is still a matter of debate. The presence of autoantibodies as well as clinical manifestations, such as interstitial lung disease, before the onset of arthritis seems to be in favour of the hypothesis that initial pathogenic events take place in tissues other than the joint. In this review article we summarize the most recent literature on extra-synovial autoimmunity triggers eventually leading to RA, with particular focus on the role of the lung. To date, anti-cyclic citrullinated peptide antibodies (ACPAs) are considered central players in RA pathogenesis and represent the gold-standard for disease diagnosis. Lungs and mucosae are exposed to environmental stimuli such as dusts and smoke which have been shown to foster citrullination of peptides in lungs thereby triggering the production of ACPA. In addition, other mechanisms of disease pathogenesis independent of citrullination play an important role. Deeper knowledge of these processes could represent a huge step forward in the management of RA, with dramatic impact on diagnosis, prevention, prognostic stratification and treatment of the disease.
类风湿关节炎（RA）的发病机制尚未完全阐明，炎症起始部位仍存在争议。在关节炎发作之前，自身抗体的存在以及间质性肺疾病等临床表现似乎支持初始致病事件发生在关节以外组织的假说。在这篇综述文章中，我们总结了关于最终导致RA的滑膜外自身免疫触发因素的最新文献，特别关注肺的作用。迄今为止，抗环瓜氨酸肽抗体（ACPAs）被认为是RA发病机制的核心因素，也是疾病诊断的金标准。肺和黏膜暴露于诸如灰尘和烟雾等环境刺激下，这些刺激已被证明会促进肺中肽的瓜氨酸化，从而触发ACPA的产生。此外，其他与瓜氨酸化无关的疾病发病机制也起着重要作用。对这些过程的更深入了解可能是RA管理方面的巨大进步，对该疾病的诊断、预防、预后分层和治疗产生重大影响。
