巨噬细胞极化失衡与类风湿关节炎疾病活动及骨侵蚀的相关性

Association of macrophage polarization imbalance with disease activity and bone erosion in rheumatoid arthritis

目的不同组织体液中巨噬细胞极化情况可能存在差异,进一步深入研究RA患者滑膜组织中巨噬细胞极化的情况尤为必要。文中观察类风湿关节炎(RA)患者滑膜组织中巨噬细胞极化的情况,研究巨噬细胞表型与RA疾病活动及骨侵蚀的相关性。方法回顾性分析95例RA、76例膝骨关节炎和18例创伤性膝关节炎患者的滑膜组织中巨噬细胞表型的特点。采用Spearman秩相关分析CD68^(+)iNOS^(+)滑膜巨噬细胞(SMs)、CD68^(+)CD206^(+)SMs和CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs与RA疾病活动指标、改良疾病活动性标准(DAS28)(3变量)评分及Larsen诊断分级的相关性;应用受试者工作特性曲线(ROC)评价巨噬细胞表型对RA疾病诊断和活动度诊断的效能。结果RA患者的滑膜组织中CD68^(+)iNOS^(+)SMs和CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs明显高于膝骨关节炎和创伤性膝关节炎患者,CD68^(+)CD206^(+)SMs则反之(P<0.01)。CD68^(+)iNOS^(+)SMs与类风湿因子、抗环瓜氨酸多肽抗体、C反应蛋白、红细胞沉降率及DAS28-3评分呈正相关(r=0.539、0.616、0.680、0.768、0.922,P<0.01)。CD68^(+)iNOS^(+)SMs、CD68^(+)CD206^(+)SMs和CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs皆与Larsen诊断分级相关(r=0.465、-0.263、0.353,P<0.01)。CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs和CD68^(+)iNOS^(+)SMs的曲线下面积均为0.983。结论CD68^(+)iNOS^(+)SMs在RA患者滑膜组织中居于优势,与RA患者疾病活动和骨侵蚀显著相关。CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs和CD68^(+)iNOS^(+)SMs分别在RA疾病诊断和活动度诊断方面具有较高效能。

Objective This study aims to observe the polarization of macrophages in synovial tissues of patients with rheumatoid arthritis(RA),and to study the correlation between macrophage phenotype and disease activity and bone erosion.Methods The characteristics of macrophage phenotypes in synovium tissues of 95 patients with RA,76 patients with knee osteoarthritis,and 18 patients with traumatic knee arthritis were retrospectively analyzed.Spearman rank correlation analysis was used to analyze the association of CD68^(+)iNOS^(+)synovial macrophages(SMs),CD68^(+)CD206^(+)SMs and CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs with RA disease activity indicators,modified disease activity criteria(DAS28)(3 variables)score and Larsen diagnostic scale.Receiver operating characteristic curve(ROC)was used to evaluate the efficacy of macrophage phenotypes in the diagnosis of RA disease and activity.Results CD68^(+)iNOS^(+)SMs and CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs is significantly higher than that in patients with knee osteoarthritis and traumatic knee arthritis,CD68^(+)CD206^(+)SMs is the opposite(P<0.01).CD68^(+)iNOS^(+)SMs was positively correlated with rheumatoid factor,anti-cyclocitcitline polypeptide antibody,C-reactive protein,erythrocyte sedimentation rate and DAS283 score(r=0.539,0.616,0.680,0.768,0.922,P<0.01).CD68^(+)iNOS^(+)SMs,CD68^(+)CD206^(+)SMs and CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs were correlated with Larsen diagnostic grading(r=0.465,-0.263,0.353,P<0.01).CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs and CD68^(+)iNOS^(+)SMs both have an area under the curve of 0.983.Conclusion CD68^(+)iNOS^(+)SMs is predominant in the synovial tissue of RA patients and is significantly related to disease activity and bone erosion in RA patients.CD68^(+)iNOS^(+)SMs/CD68^(+)CD206^(+)SMs and CD68^(+)iNOS^(+)SMs have high efficiency in RA disease diagnosis and activity diagnosis respectively.