抗细胞膜DNA抗体对系统性红斑狼疮临床价值的研究

The value and clinical application of autoantibodies against cell membrane associated DNA in systemic lupus erythematosus

目的 应用间接免疫荧光法（IIF）检测SLE患者抗细胞膜DNA（cmDNA）抗体,确定血清该抗体对SLE诊断的最佳阳性阈值;探讨抗cmDNA抗体对大样本SLE患者的诊断价值.方法 采用IIF检测129例SLE患者抗cmDNA抗体,69例疾病对照组,50名健康对照,以原血清及与1∶10、1∶20、1∶40、1∶80、1∶160、1∶320、1∶640、1∶1 280稀释血清检测结果为阳性阈值,比较受试者工作特征曲线（ROC）曲线下面积（AUG）,确定血清抗cmDNA抗体对SLE诊断的最佳阳性阈值;检测435例SLE患者及192例疾病对照组、50名健康对照组血清抗cmDNA抗体,同时检测ANA、抗dsDNA抗体、抗Sm抗体和抗核小体抗体（AnuA）,比较血清抗cmDNA抗体单独或与上述抗体联合检测对SLE的诊断价值.采用t检验,四格表资料χ%2检验,配对资料McNemar χ^2检验进行统计学分析.结果 ①比较不同阳性阈值抗cmDNA抗体的AUC,以1∶40为阳性阈值的AUC最大（AUC=0.643）,以抗cmDNA抗体1∶40为阳性阈值对SLE诊断效能最佳,并作为本次研究的阳性阈值.②抗cmDNA抗体对SLE诊断的敏感性和特异性,分别为72.9％和90.7％.抗cmDNA抗体、抗dsDNA抗体、抗Sm抗体、AnuA及ANA对SLE诊断的AUC分别为0.836、0.746、0.617、0.845及0.762;分别将抗dsDNA抗体、抗Sm抗体及AnuA与抗cmDNA抗体两两联合检测,敏感性分别为85.2％、76.4％和83.8％,均明显高于上述抗体单独检测,差异有统计学意义（χ^2=109.20,243.28,12.57; P＜0.05）.结论 以Raji细胞为底物IIF检测抗cmDNA抗体,1∶40为阳性阈值是对SLE诊断的最佳效能.抗cmDNA抗体对SLE诊断的敏感性高,特异性强,可能成为SLE诊断的相对特异性抗体之一.抗cmDNA抗体与抗dsDNA抗体、抗Sm抗体及AnuA联合检测可提高对SLE诊断的敏感性.

Objective To determine the cut-off value of anti-cmDNA antibody in systemic lupus erythematosus （SLE） detected by indirect immunofluorescence assay （IIF） on human＇s B lymphoma cell line Raji,and to explore the diagnostic value of anti-cmDNA antibody in SLE.Methods We included 129 patients with SLE.As the control group,we included 69 patients with other rheumatic diseasesand 50 healthy subjects.IIF was used to detect the anti-cmDNA antibody.Different threshold levels （1∶10,1∶20,1∶40,1∶80,1∶160,1∶320,1∶640,1∶1 280） for positive results were calculated by the areas under the receiver operating characteristic curve （ROC） area under curve （AUC）.By comparing the AUC of all titers of anti-cmDNA antibody in SLE,the best diagnosis cut-off value for SLE was determined.Then anti-cmDNA antibody was tested in 435 patients with SLE,192 patients with other rheumatic diseases,and 50 healthy blood donors The diagnostic value of anti-cmDNA antibody in SLE was evaluated.At the same time,ANA and anti-dsDNA were measured by IIF.Anti-Sm was measured by immuno-doublediffusion and Western blotting.AnuA was measured by enzyme linked immunosorbent assay.T-test,four-table χ^2 test and McNemar χ^2 test were used for statistical analysis.Results ① By comparing the AUC of all titers of anti-cmDNA antibody in SLE,the best diagnosis cut-off value for SLE was determined as 1∶40 （AUC=0.643）.② The sensitivity and specificity of anti-cmDNA antibody for SLE was 72.9% and 90.7% respectively.The AUC of anti-cmDNA,anti-dsDNA,anti-Sm,AnuA and ANA for SILE was 0.836,0.746,0.617,0.845 and 0.762 respectively.The sensitivities of anti-dsDNA,anti-Sm and AnuA were much higher when combined with anti-cmDNA than those detected individually （χ^2=109.20,243.28,12.57; P〈0.05）.Conclusion We concluded that the best diagnosis cut-off value of anticmDNA for SLE has been determined as 1∶40.Anti-cmDNA antibody has high sensitivity and specificity in SLE.Combined anti-cmDNA and other autoantibodies might further improve the diagnostic sensitivity in SLE.