Department of Medicine, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea.
Int J Mol Sci. 2023 Sep 25;24(19):14509. doi: 10.3390/ijms241914509.
Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast-myofibroblast transition, epithelial-mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.
间质性肺病（ILD）是类风湿关节炎（RA）最严重的关节外并发症之一，可增加 RA 的死亡率。由于 RA-ILD 的发病机制仍不清楚，因此尚未确定合适的治疗策略和生物标志物。因此，本综述的目的是总结和分析关于 RA-ILD 的病因和发病机制的报告数据。RA-ILD 的发病率随年龄增长而增加，一般男性高于女性，且在具有特定遗传变异和种族的患者中更高。与 RA-ILD 风险增加相关的生活方式因素包括吸烟和接触污染物。存在抗环瓜氨酸肽抗体、高 RA 疾病活动度和类风湿因子阳性也会增加 RA-ILD 的风险。我们还根据发表的 RA-ILD 的动物和人类研究的临床前和临床模型，探讨了生物过程（如成纤维细胞-肌成纤维细胞转化、上皮-间充质转化和免疫过程）、信号通路（如 JAK/STAT 和 PI3K/Akt）以及 RA 组织病理学在 RA-ILD 发病机制中的作用。
