IL-2、IL-6因子与肠道菌群紊乱的交互作用对类风湿关节炎合并肺间质疾病的关联分析  

Study on interaction of IL-2,IL-6 factors and intestinal flora disorder in patients with rheumatoid arthritis complicated with interstitial lung disease

作　　者：刘彦洁 李良霄[2] 陈庆娜 马利娜 肖冉冉 LIU Yanjie;LI Liangxiao;CHEN Qingna;MA Lina;XIAO Ranran(Department of Infectious DiseasesⅠ,Shijiazhuang People's Hospital,Shijiazhuang 050031,China;Department of Infectious Diseases,the First Handan Hospital,Handan 056002,China;Department of Urology,the Fourth Handan Hospital,Handan 056002,China)

机构地区：[1]石家庄市人民医院感染性疾病一科,石家庄050031 [2]邯郸市第一医院感染性疾病科,邯郸056002 [3]邯郸市第四医院泌尿外科,邯郸056002

出　　处：《中国免疫学杂志》2025年第4期959-966,共8页Chinese Journal of Immunology

基　　金：石家庄市科学技术研究与发展计划(211460753)。

摘　　要：目的:探讨IL-2、IL-6因子与肠道菌群紊乱的交互作用对类风湿关节炎合并肺间质疾病(RA-ILD)的关联分析。方法:收集2021年6月至2022年6月于石家庄市人民医院确诊的100例RA患者为研究对象,根据肺部CT结果及临床表现分为RA-ILD组(合并ILD,27例)和RA-noILD组(未合并ILD,73例)。收集所有受试者粪便样本,培养并检测肠道菌群水平;提取粪便样本DNA,PCR扩增细菌16S rDNA,获得肠道菌群DGGE图谱,分析肠道细菌Shannon-Wiener指数、均匀度、丰富度指标,对图像进行聚类分析,分析两组患者肠道菌群结构的差异。比较两组患者的一般资料、临床症状、实验室指标及肠道菌群相关指标。多因素Logistic回归分析影响RA患者发生ILD的独立因素。使用Spearman相关分析血清IL-2、IL-6水平与肠道菌群相关指标的相关性。使用Cox比例风险回归分析影响RA-ILD患者转归的独立因素。结果:吸烟、年龄≥53.77岁、抗CCP抗体≥334.60 RU/ml、IL-6≥199.47 ng/ml、IL-2<3.10 ng/ml、丰富度<18.39、Shannon-Wiener指数<2.88、双歧杆菌<7.27 CFU/g、脆弱类杆菌<7.75 CFU/g、H_(max)<3.14、菌群均匀度<0.92是RA患者发生ILD的独立影响因素。RA-ILD患者血清IL-6水平与丰富度、Shannon-Wiener指数、H_(max)、菌群均匀度呈明显负相关(P<0.05),血清IL-2水平与丰富度、Shannon-Wiener指数、H_(max)、菌群均匀度呈明显正相关(P<0.05)。吸烟、年龄、抗CCP抗体、IL-6、IL-2、丰富度、Shannon-Wiener指数、双歧杆菌、脆弱类杆菌、H_(max)、菌群均匀度是影响RA-ILD患者转归的独立因素(P<0.05)。结论:吸烟、年龄、抗CCP抗体、IL-6、IL-2、丰富度、Shannon-Wiener指数、双歧杆菌、脆弱类杆菌、H_(max)、菌群均匀度对RA-ILD具有显著的诊断和预后评估价值。RA-ILD患者肠道微生物群落改变,肠道细菌数量及结构变化可能是RA患者并发ILD的关键因素。Objective:To explore the interaction of IL-2,IL-6 factors and intestinal flora disorder in patients with rheumatoid arthritis complicated with interstitial lung disease(RA-ILD).Methods:A total of 100 RA patients diagnosed at Shijiazhuang People's Hospital from June 2021 to June 2022 were enrolled and divided into the RA-ILD group(with ILD,n=27)and RA-noILD group(without ILD,n=73)according to the results of pulmonary CT and clinical manifestations.Fecal samples were collected from all participants,and intestinal flora levels were cultured and analyzed.Bacterial DNA was extracted from fecal samples,and the 16S rDNA gene was amplified by PCR to generate DGGE profiles of gut microbiota.The Shannon-Wiener index,evenness,and richness of intestinal bacteria were calculated.Cluster analysis was performed to compare structural differences in gut microbiota between the groups.Demographic characteristics,clinical symptoms,laboratory parameters,and intestinal flora-related indicators were compared between the groups.Multivariate Logistic regression analysis was conducted to identify independent risk factors for ILD development in RA patients.Spearman correlation analysis was used to evaluate relationships between serum IL-2,IL-6 levels and gut microbiota parameters.Cox proportional hazards regression analysis was performed to determine independent factors influencing disease progression in RA-ILD patients.Results:Smoking,age≥53.77 years old,anti-CCP antibody≥334.60 RU/ml,IL-6≥199.47 ng/ml,IL-2<3.10 ng/ml,richness<18.39,Shannon-Wiener index<2.88,Bifidobacterium<7.27 CFU/g,Bacteroides fragilis<7.75 CFU/g,H_(max)<3.14 and flora uniformity<0.92 were independent factors affecting the occurrence of ILD in patients with RA.In patients with RA-ILD,serum IL-6 level was negatively correlated with richness,Shannon-Wiener index,H_(max) and flora evenness,while serum IL-2 level was positively correlated with richness,Shannon-Wiener index,H_(max) and flora evenness.Smoking,age,anti-CCP antibody,IL-6,IL-2,richness,Shannon-Wiener inde

关 键 词：类风湿关节炎合并肺间质疾病 肠道菌群 IL-2 IL-6 

分 类 号：R593.22[医药卫生—内科学]