Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies
Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies
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DOI：
10.1007/s40618-016-0478-9
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发表时间：
2016-10-01
影响因子：
5.4
通讯作者：
Kahaly, G. J.
中科院分区：
文献类型：
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作者：
Diana, T.;Wuester, C.;Kahaly, G. J.
目的 TSH 受体 (TSHR) 抗体 (Ab) 可以通过结合或生物测定进行测量。比较了五种结合和两种生物测定的灵敏度和特异性。方法用报告生物测定法测量TSHR阻断(TBAb)和TSHR刺激(TSAb)抗体。阻断活性定义为相对于仅用 bTSH 诱导的荧光素酶表达的抑制百分比。 TSAb 以样本与参考比的百分比 (SRR%) 报告。使用 Kronus、Dynex、Kryptor、Cobas 和 Immulite 测量 TSHR 结合抑制性免疫球蛋白 (TBII)。 结果 纳入 60 名格雷夫斯病 (GD) 患者、20 名桥本甲状腺炎 (HT) 患者和 20 名健康对照 (C)。 C 在所有测定中均呈阴性（特异性 100%），而所有 60 名甲亢 GD 患者在 TSAb 生物测定中均呈阳性（敏感性 100%）。在这 60 名 GD 患者中，有 20 名 TSAb 阳性率较低 (SRR% 140-279)，但使用 Kronus、Dynex、Kryptor、Cobas 和 Immulite 时分别只有 20 名 (100%)、7 名 (35%)、9 名 (45%)、11 名 (55%) 和 18 名 (90%) 患者呈 TBII 阳性。在 20 名中度 TSAb 阳性 (SRR% 280-420) 患者中，分别有 20 名 (100%)、14 名 (70%)、13 名 (65%)、16 名 (80%) 和 19 名 (95%) 患者 TBII 检测呈阳性。高（SRR% > 420）TSAb 阳性患者均为 TBII 阳性。所有 20 名甲状腺功能减退症 HT 患者在生物测定中均检测出 TBAb 阳性（敏感性 100%），同时分别有 20 名（100%）、18 名（90%）、20 名、20 名和 18 名患者检测出 TBII 阳性。使用两个光度计获得的结果与 TSAb 阳性（r = 0.99，p < 0.001）、TBAb 阳性（r = 0.88，p < 0.001）和 C（r = 0.86，p < 0.001）相关。 TSAb 和 TBAb 之间的结合测定均无差异。结论 TSHR-Ab 的结合测定和生物测定之间的灵敏度差异很大。
Purpose TSH-receptor (TSHR) antibodies (Ab) can be measured with binding or bio-assays. Sensitivity and specificity of five binding and two bio-assays were compared.Methods TSHR-blocking (TBAb) and TSHR-stimulating (TSAb) Ab were measured with reporter bio-assays. Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bTSH alone. TSAb was reported as percentage of specimen-to-reference ratio (SRR%). TSHR-binding inhibitory immunoglobulins (TBII) were measured with Kronus, Dynex, Kryptor, Cobas, and Immulite.Results Sixty patients with Graves' disease (GD), 20 with Hashimoto's thyroiditis (HT), and 20 healthy controls (C) were included. C tested negative in all assays (specificity 100 %) while all 60 hyperthyroid GD patients tested positive in the TSAb bio-assay (sensitivity 100 %). Among these 60 GD patients, 20 had low TSAb positivity (SRR% 140-279), but were TBII positive in only 20 (100 %), 7 (35 %), 9 (45 %), 11 (55 %), and 18 (90 %) using the Kronus, Dynex, Kryptor, Cobas, and Immulite, respectively. In 20 moderate TSAb-positive (SRR% 280-420) patients, TBII tested positive in 20 (100 %), 14 (70 %), 13 (65 %), 16 (80 %), and 19 (95 %), respectively. The high (SRR% > 420) TSAb-positive patients were all TBII positive. All 20 hypothyroid HT patients tested TBAb positive (sensitivity 100 %) in the bio-assay while they tested TBII positive in 20 (100 %), 18 (90 %), 20, 20, and 18, respectively. Results obtained with two luminometers correlated for TSAb positive (r = 0.99, p < 0.001), TBAb positive (r = 0.88, p < 0.001), and C (r = 0.86, p < 0.001). None of the binding assays differentiated between TSAb and TBAb.Conclusions Sensitivity is highly variable between binding and bio-assays for TSHR-Abs.