国产化学发光免疫试剂检测TRAb的性能评估及临床应用价值

Performance Evaluation and Clinical Application Value of Domestic Chemiluminescence Immunoassay Reagent in Detecting Thyrotropin Receptor Antibody

目的对某国产化学发光免疫(chemiluminescence immunoassay,CLIA)试剂检测促甲状腺激素受体抗体(thyrotropin receptor antibody,TRAb)的性能进行评估,并探讨其临床应用价值。方法参考美国临床实验室标准化协会系列文件,对国产CLIA试剂检测血清TRAb的精密度、特异度、正确度、线性范围以及参考区间进行评价;收集2019年6~12月在陕西省人民医院内分泌科就诊的168例甲状腺相关疾病患者(格雷夫斯病121例;桥本氏甲状腺炎22例;非自身免疫性良性甲状腺结节19例;分化型甲状腺癌6例)及60例健康体检者的血清样本,分别用国产CLIA试剂和进口电化学发光免疫(electrochemiluminescence immunoassay,ECLIA)试剂检测血清TRAb水平,对两种试剂的检测结果进行相关性和一致性评价,并评价国产TRAb CLIA试剂诊断格雷夫斯病的效能。结果国产CLIA试剂检测高、低水平TRAb的重复性(coefficient of variation,CV)分别为2.04%和6.08%,实验室内不精密度分别为2.62%和6.50%;检测2000 IU/ml的甲状腺球蛋白抗体、2000 IU/ml的甲状腺过氧化物酶抗体、1000 mIU/L的促甲状腺激素、10000 IU/L的促黄体生成素、10000 IU/L的促卵泡生成素和50000IU/L的人绒毛膜促性腺激素,结果均<0.3 IU/L;高、低水平国际标准品的相对偏差分别为5.05%和1.33%;在0.65 IU/L~44.21 IU/L之间呈良好的线性关系(r^(2)=0.999,P﹤0.0001);参考区间验证结果显示20例健康体检者血清TRAb水平均<2.0 IU/L;两种试剂检测结果相关性r^(2)=0.9396,斜率为1.058;定性分析结果显示,两种试剂检测结果的总体符合率为97.37%,Kappa值为0.947(P﹤0.0001);国产TRAb CLIA试剂诊断格雷夫斯病的灵敏度为95.04%。结论国产CLIA试剂检测血清TRAb的各项性能指标均表现良好,能够满足临床要求,有较好的临床应用前景。

Objective To evaluate the performance of a domestic chemiluminescence immunoassay(CLIA)reagentin detecting of Thyrotropin receptor antibody(TRAb)and furtherly explore its clinical application value.Methods According to the series documents of American Clinical and Laboratory Standards Institute(CLSI),evaluated the precision,specificity,accuracy,linear range and reference interval of the domestic CLIA reagent in detecting serumTRAb.The serum samples in this study were collected from patients who were admitted to department of Endocrinology,Shaanxi Provincial People’s Hospital from June to December 2019(121 cases of Graves’disease,22 cases of Hashimoto’s thyroiditis,19 cases of non-autoimmune benign thyroid nodule,and 6 cases of differentiated thyroid cancer)and 60 healthy persons.All serum samples were subjected to analyze the TRAb levels by CLIA assay and electrochemiluminescence immunoassay(ECLIA)assay.A comparative evaluation between the two assays was performed and the concordance of qualitative results was also assessed.Additionally,the diagnostic efficacy of CLIA assay for detecting TRAb in Graves’disease was also evaluated.Results The repeatability and within-laboratory imprecision(%coefficient of variation)of the CLIA were 6.08%and 6.50%at 1.87 IU/L,and 2.04%and 2.62%at 24.07 IU/L,respectively.The results of detecting 2000IU/mL thyroglobulin antibody,2000 IU/mL thyroid peroxidase antibody,1000 mIU/L thyroid stimulating hormone,10000IU/L luteinizing hormone,10000 IU/L follicle stimulating hormone,and 50000IU/L of human chorionic gonadotropin were all less than 0.3IU/L.The relative biases of high and low levels of World Health Organization international standard 2nd international standard for thyroid stimulating antibody were 5.05%and 1.33%,respectively.Meanwhile,the 0.65~44.21 IU/L range of CLIA assay showed a good linear(r^(2)=0.999,P﹤0.0001).The serum TRAb levels of 20 healthy people were less than 2.0 IU/L.The two assays had a good correlation(r^(2)=0.9396,slope=1.058).The overall coincidence rate of the two assays was 97.37%.The Kappa value was 0.947(P<0.0001).The sensitivity of CLIA assay in detecting TRAb for Graves’disease was 95.04%.Conclusion The main performance of the domestic TRAb CLIA reagentmeets the requirements of the relevant standards,which can satisfy the clinical requirements.