Bernardinello Nicol, Zen Margherita, Castelli Gioele, Cocconcelli Elisabetta, Balestro Elisabetta, Borie Raphaël, Spagnolo Paolo
Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Rheumatology Unit, Department of Medicine, University of Padua, Padova, Italy.
Front Med (Lausanne). 2025 Feb 24;12:1542400. doi: 10.3389/fmed.2025.1542400. eCollection 2025.
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects millions of people worldwide and is characterized by persistent inflammation, pain, and joint destruction. In RA, the dysregulation of the immune system is well documented. However, the genetic basis of the disease is not fully understood, especially when extra-articular organs are involved. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with RA. Notably, RA-ILD shares several risk factors with idiopathic pulmonary fibrosis (IPF), namely male gender, smoking history, usual interstitial pneumonia (UIP) pattern of fibrosis, and association with the rs35705950 polymorphism. In addition, other genetic susceptibilities are reported in RA-ILD for some HLA alleles and other less studied polymorphisms. However, the pathobiology of RA-ILD, particularly whether and to what extent genetic and environmental factors interact to determine the disease, remains elusive. In this review, we summarize and critically discuss the most recent literature on the genetics and pathogenesis of RA-ILD. The main clinical aspects of RA-ILD are also discussed.
类风湿关节炎（RA）是一种全身性自身免疫性疾病，全球数百万人受其影响，其特征为持续性炎症、疼痛和关节破坏。在类风湿关节炎中，免疫系统失调已有充分记载。然而，该疾病的遗传基础尚未完全明确，尤其是当关节外器官受累时。间质性肺疾病（ILD）是类风湿关节炎患者发病和死亡的主要原因。值得注意的是，类风湿关节炎相关间质性肺疾病（RA-ILD）与特发性肺纤维化（IPF）有几个共同的危险因素，即男性、吸烟史、普通型间质性肺炎（UIP）纤维化模式以及与rs35705950多态性的关联。此外，对于某些HLA等位基因和其他研究较少的多态性，类风湿关节炎相关间质性肺疾病也有其他遗传易感性报道。然而，类风湿关节炎相关间质性肺疾病的病理生物学，特别是遗传和环境因素是否以及在多大程度上相互作用以决定该疾病，仍然不清楚。在这篇综述中，我们总结并批判性地讨论了关于类风湿关节炎相关间质性肺疾病遗传学和发病机制的最新文献。同时也讨论了类风湿关节炎相关间质性肺疾病的主要临床方面。
