Liu C, Hermsen D, Domberg J, Graeber C, Hautzel H, Duan Y, Xu K F, Liu C P, Mao X D, Cupisti K, Scherbaum W A, Schott M
Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Horm Metab Res. 2008 Jul;40(7):479-83. doi: 10.1055/s-2008-1077051. Epub 2008 May 26.
Previously, a new procedure for measuring serum TSH receptor autoantibodies (TRAb) was reported in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 to TSHR-coated ELISA plate wells (TRAb ELISA). The aim of the present study was to evaluate the clinical performance of this assay in comparison to the second generation TRAb assay (TRAb LIA) based on the recombinant human TSH-receptor and chemiluminescence technology (TRAb LIA). Among the 158 patients, 84 patients suffered from Graves' disease (GD), 34 patients had Hashimoto's thyroiditis (HT), and 40 patients had euthyroid nodular thyroid disease (NTD) without signs of autoimmunity. TRAb measurements were performed according to the manufacturer's instructions. Out of 84 GD patients, 80 (95.2%) were TRAb positive as detected by the TRAb LIA. One GD patient had TRAb values within the grey zone (1.0-1.5 IU/l). All patients with HT and NTD were negative except in 6 (8.1%) cases whose TRAb values were within the grey zone. On the basis of the recommended cutoff value (TRAb 1.0 IU/l), the TRAb ELISA found 78 of 84 (92.9%) GD patients to be TRAb positive. None of the patients with HT, but two cases (5.0%) with NTD were TRAb positive. The diagnostic sensitivity of the TRAb LIA and TRAb ELISA assays was 95.2 and 92.9%, while the specificity was 100% and 97.3%, respectively. There was a close correlation (r=0.968, p<0.0001) between both assays in 84 patients with GD. Additionally, the between-run imprecision close to the cutoff limit was assessed. The calculated between-run coefficient of variation (CV) of the TRAb ELISA was 28.2% at the recommended cutoff value of 1.0 IU/l. Due to the evaluated imprecision data we propose a higher cutoff value correlating with a between-run CV of 20% (functional assay sensitivity). Our results indicate that due to a worse imprecision the TRAb ELISA has a slightly lower sensitivity and specificity compared to the TRAb LIA assay. These findings suggest that the M22 monoclonal antibody-based TRAb ELISA is not as reliable as other second generation TRAb assays in the diagnosis of Graves' diseases.
此前，有报道称一种测量血清促甲状腺激素受体自身抗体（TRAb）的新方法，该方法中自身抗体可抑制人单克隆促甲状腺抗体M22与包被有促甲状腺激素受体（TSHR）的酶联免疫吸附测定（ELISA）板孔的结合（TRAb ELISA）。本研究的目的是与基于重组人促甲状腺激素受体和化学发光技术的第二代TRAb检测方法（TRAb LIA）相比，评估该检测方法的临床性能。158例患者中，84例患有格雷夫斯病（GD），34例患有桥本甲状腺炎（HT），40例患有甲状腺功能正常的结节性甲状腺疾病（NTD）且无自身免疫迹象。TRAb检测按照制造商说明进行。在84例GD患者中，TRAb LIA检测发现80例（95.2%）TRAb呈阳性。1例GD患者的TRAb值处于灰区（1.0 - 1.5 IU/l）。除6例（8.1%）TRAb值处于灰区的患者外，所有HT和NTD患者均为阴性。基于推荐的临界值（TRAb 1.0 IU/l），TRAb ELISA发现84例GD患者中有78例（92.9%）TRAb呈阳性。HT患者均无TRAb阳性，但有2例（5.0%）NTD患者TRAb呈阳性。TRAb LIA和TRAb ELISA检测的诊断敏感性分别为95.2%和92.9%，而特异性分别为100%和97.3%。在84例GD患者中，两种检测方法之间存在密切相关性（r = 0.968，p < 0.0001）。此外，还评估了接近临界值时的批间不精密度。在推荐的临界值1.0 IU/l时，TRAb ELISA计算得出的批间变异系数（CV）为28.2%。基于评估的不精密度数据，我们提出一个更高的临界值，其与批间CV为20%相关（功能检测敏感性）。我们的结果表明，由于不精密度较差，与TRAb LIA检测相比，TRAb ELISA的敏感性和特异性略低。这些发现表明，基于M22单克隆抗体的TRAb ELISA在格雷夫斯病的诊断中不如其他第二代TRAb检测方法可靠。
