结缔组织病相关间质性肺疾病危险因素及发病机制研究进展
Advances in research on the risk factors and pathogenesis of connective tissue disease-associated interstitial lung disease
邵新淋 1朱雪梅 2曹华1
作者信息
- 1. 上海交通大学医学院附属瑞金医院 皮肤科,上海 200025
- 2. 上海交通大学医学院附属瑞金医院 呼吸与危重症科,上海 200025
- 折叠
摘要
结缔组织病相关间质性肺疾病(connective tissue disease-associated interstitial lung disease,CTD-ILD)是一组由结缔组织病引起的肺部疾病,发病率为10%～50%,死亡率高达20%.CTD-ILD的临床表现和影像学特征异质性大,其发病原因尚不完全清楚,了解其危险因素及发病机制对于疾病的诊断、治疗及预后管理至关重要.CTD-ILD的危险因素多样.遗传因素中,CTD-ILD患者的端粒相关基因(包括TERT、RTEL1、PARN和SFTPC)突变率是正常人的3倍,携带MUC5B启动子突变的患者发病风险可能增加至正常人的2倍以上,TOLLIP和HLA-DRB1基因突变也与CTD-ILD患者的疾病易感性增加有关.治疗CTD的药物也可能增加ILD的发病风险.合并感染的患者出现重症CTD-ILD风险更高(OR值为1.34～2.73),死亡风险也更高(OR值为1.2～4.3).约三分之一的CTD-ILD患者合并胃食管反流病.长期吸烟和暴露于空气污染的环境中均可诱发CTD-ILD.CTD-ILD的发病机制涉及免疫系统的异常,主要表现为自身抗体产生(如系统性硬化症相关抗体和肌炎特异性抗体等)、免疫细胞(如中性粒细胞、自然杀伤细胞、Th2和Th17等)功能异常以及细胞因子(如TNF-α、TGF-β、IL-6和IL-8等)大量释放,可见于50%以上的CTD-ILD患者中.CTD-ILD的危险因素及发病机制复杂,构建CTD-ILD的风险预测模型,可以更精准地识别高风险个体,为疾病的预防和治疗提供新策略,从而改善患者的长期预后.
Abstract
Connective tissue disease-associated interstitial lung disease(CTD-ILD)is a group of lung diseases caused by connective tissue diseases,with an incidence ranging from 10%to 50%and a mortality rate as high as 20%.The clinical manifestations and imaging features are heterogeneous.However,its pathogenesis is not fully understood.Exploring the risk factors and pathogenesis is crucial for the diagnosis,treatment and prognosis management of CTD-ILD.The risk factors for CTD-ILD are diverse.Firstly,genetic factors play an important role in pathogenesis.Mutation rate of telomere-re-lated genes(including TERT,RTEL1,PARN,and SFTPC)in CTD-ILD patients is three times as high as that of general population.The risk of developing CTD-ILD in patients with the mutation in MUC5B promoter is more than twice that of normal people.The mutations in the TOLLIP and HLA-DRB1 are also associated with increased disease susceptibility.In addition,medications used to treat CTD may also increase the risk of developing ILD.Approximately one-third of CTD-ILD patients also suffer from gastroesophageal reflux disease.Chronic smoking and exposure to air pollution may also increase the incidence of CTD-ILD.CTD-ILD patients with infections have a higher risk of severe outcomes(OR 1.34-2.73)and in-creased mortality risk(OR 1.2-4.3).The pathogenesis of CTD-ILD involves the abnormality of the immune system,which is mainly manifested in the production of autoantibodies(such as systemic sclerosis-related antibodies and myositis-specific antibodies),the dysfunction of immune cells(such as neutrophils,natural killer cells,Th2 and Th17)and the extensive re-lease of cytokines(such as TNF-α,TGF-β,IL-6 and IL-8),which exist in more than 50%of CTD-ILD patients.The risk fac-tors and pathogenesis of CTD-ILD are complex.Risk prediction model based on these factors may help identify high-risk in-dividuals accurately,which can provide new strategies for the prevention and treatment of the disease,improve the long-term prognosis of patients.
关键词
结缔组织病/间质性肺疾病/危险因素/发病机制Key words
Connective tissue disease/Interstitial lung disease/Risk factors/Pathogenesis引用本文复制引用
基金项目
国家自然科学基金面上项目(81573037)
国家自然科学基金面上项目(81872523)
国家自然科学基金面上项目(82073432)
国家自然科学基金面上项目(82373464)
国家临床重点专科建设项目(2012649)
上海市科委医学引导类项目(134119a6100)
上海申康医院发展中心临床创新三年行动计划(16CR3084B)
上海交通大学医学院高峰学科(20172009)
上海市医苑新星青年医学人才培养资助计划杰出青年医学人才类(2019)()
上海交通大学医学院高水平创新团队(二期)协同团队(2021)()
出版年
2024
国家科技期刊平台
NSTL
万方数据