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抗突变型瓜氨酸波形蛋白抗体对类风湿关节炎诊断的补充价值

Anti-mutant citrullinated vimentin antibody in the diagnosis of rheumatoid arthritis

摘要目的 探讨抗突变型瓜氨酸波形蛋白(MCV)抗体在类风湿关节炎(RA)中的诊断价值以及与关节破坏程度、关节外表现和重叠综合征的相关性.方法 回顾性研究.收集2017年6月至8月,在北京协和医院进行抗MCV抗体、抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、红细胞沉降率(ESR)和超敏C反应蛋白(CRP)检查的所有患者结果记录共837例.依据1987年美国风湿病学会RA分类标准诊断为RA 323例,其中男59例,女264例,平均年龄51(43~60)岁;依据RA患者是否重叠其他自身免疫病,有无关节外受累分为单纯关节受累的RA组258例,其中男47例,女211例,平均年龄50(43~59)岁;重叠综合征组14例,其中男1例,女13例,平均年龄36(24~60)岁;关节外表现组51例,其中男11例,女40例,平均年龄59(47~64)岁;依据2010年RA诊断及治疗指南中影像学X线改变对关节破坏程度分4期;本文中在北京协和医院同时进行X线检查的RA患者有203例,其中Ⅰ期(早期)为早期组88例,男21例,女67例,平均年龄48(38~55)岁;Ⅱ期(中期)、Ⅲ期(严重期)和Ⅳ期(终末期)为进展期组115例,其中男19例,女96例,平均年龄53(46~62)岁.应用Mann-WhitneyU检验、x2检验、受试工作者曲线ROC和Spearman秩相关进行统计学分析.结果 确诊RA患者中,抗MCV抗体、抗CCP抗体和RF同时阳性199(61.6%)例;单独抗MCV抗体阳性42(13%)例,高于抗CCP抗体(1例,0.3%)和RF(7例,2.2%),差异有统计学意义(P<0.001,P<0.001).应用ROC曲线得到MCV=35.95 U/ml为最佳界值点时,曲线下面积(AUC)=0.867,抗体敏感度(80.5%)和特异度(80.9%)最高.进展期组抗MCV抗体、抗CCP抗体和RF检测值[682.8(106.4~1000.0),407(4.0~1536.0),82.8(21.1~244.9)]分别高于早期组[114.5(28.5~1000.0),62.5(5.0~1020.7),50.1(6.7~127.1)],差异有统计学意义(P<0.05,P<0.05,P<0.05).抗MCV抗体、抗CCP抗体和RF与进展期关节破坏程度成正相关(r=0.229,P<0.05;r=0.187,P<0.05;r=0.167,P<0.05);抗MCV抗体和抗CCP抗体与关节外表现成正相关(r=0.152,P<0.05;r=0.136,P<0.05).结论 抗MCV抗体在RA患者中有更高的敏感度,对抗CCP抗体和RF阴性的患者有补充诊断价值;检测值高的抗MCV抗体和抗CCP抗体与RA病情进展和关节外器官受累的发生有关.

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abstractsObjective This study aimed to assess the diagnostic value of anti-mutated citrullinated vimentin (MCV) antibodies in rheumatoid arthritis (RA) and its correlation with disease progression, extra-articular manifestations and overlap syndrome. Methods Retrospective Studies. Clinical data of 837 patients in PekingUnionMedicalCollegeHospitalfrom June to August 2017 were collected, including the result of anti-MCV, anti-cyclic citrullinated peptide (anti-CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and High-sensitivity-C-reactive protein (CRP). According to the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis, there were 323 patients diagnosed with RA, including 59 males and 264 females with the average age of 51 years. According to whether the RA patients have overlap syndrome with other autoimmune disease (AID) or have extra-articular manifestations, 258 cases were categorized into RA group, including 47 males and 211 females with the average age of 50 years; 14 cases were categorized into the group of overlap syndrome, including 1 male and 13 females with the average age of 36 years;51 cases were categorized into the group of extra-articular manifestations, including 11 males and 40 females with the average age of 59 years.According to 2010 rheumatoid arthritis classification criteria for destruction in joints, the radiographic changes were divided into 4 stages. There were 203 casesenrolled in our study, 88 caseswere fitted into early stage group (stage I)including 21 males and 67 females with the average age of 48 years; 115 caseswere fitted into progressive stage group, which compromisedstageⅡ (interim stage), stage Ⅲ (severe stage) and stage Ⅳ(final stage) cases, including 19 males and 96 females with the average age of 53 years. Mann-Whitney U test, x2 test, Receiver operating characteristic (ROC) curves and Spearmancorrelation coefficientwere used in Statistical analysis. Results Ⅰ Amongdiagnosed RA patients, 199 (61.6%) cases were positive for anti-MCV, anti-CCP and RFsimultaneously, 42 (13%) cases were positive for anti-MCV, which was higher than anti-CCP positive (1 cases, 0.3%) or RF positive (7cases, 2.2%). The difference was statistically significant(P<0.001, P<0.001). ⅡROC was calculated and MCV=35.95 U/ml was used as best-fit cut-off value. The AUC for anti-MCV was 0.867, while the sensitivity was 80.5%and specificity was 80.9%.ⅢThe detection levels of anti-MCV (682.8 (106.4-1000.0)), anti-CCP (407 (4.0-1536.0)) and RF (82.8 (21.1-244.9)) in the group of progressive stage were higher than those in the group of early stage (114.5 (28.5-1000.0), 62.5 (5.0-1020.7), 50.1 (6.7-127.1)), which showed a significant difference(P<0.05, P<0.05, P<0.05). The anti-MCV, anti-CCP and RF were positively related to the degree of joint destruction (r=0.229, P<0.05;r=0.187, P<0.05;r=0.167, P<0.05);anti-MCV and anti-CCP were positively related to extra-articular manifestation (r=0.152, P<0.05;r=0.136, P<0.05). Conclusion Anti-MCV antibodies are more sensitive in patients with RA, and have complementary diagnostic value for anti-CCP and RF-negative patients; high levels of anti-MCV and anti-CCP in RA patients are associated with RA progression and extra-articular involvement.

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