Department of Biotechnology, University of Turku, Turku, Finland.
Clin Chem. 2013 Mar;59(3):512-8. doi: 10.1373/clinchem.2012.194860. Epub 2013 Jan 3.
Autoantibodies to cardiac troponins (cTnAAbs) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays for the diagnosis of myocardial infarction. Therefore, we determined the cTnI binding sites and IgG subclasses of circulating cTnAAbs.
We studied epitope specificity with sandwich-type immunoassays by measuring the recovery of troponin complex added to 10 cTnAAb-negative and 10 cTnAAb-positive sera from healthy volunteers. To study the IgG subclasses, we analyzed admission and 3-month follow-up sera from chest pain patients with a reference assay measuring total IgG (14 cTnAAb negative and 14 cTnAAb positive at 3 months) and with 4 subclass-specific assays measuring exclusively IgG subclasses 1-4.
Mean recoveries of troponin complex in cTnAAb-positive samples for single cTnI epitopes ranged from 37% to 211%, being lowest for the cTnI midfragment (aa 30-110). However, the lowest sample-specific recoveries, 4%-92%, showed that none of the studied epitopes completely escaped the cTnAAb-related interference. Eight chest pain patients of the cTnAAb-positive group became positive between sampling points, and according to all 5 cTnAAb assays, specific signals were generally higher at follow-up. IgG4, with the highest prevalence, was detected in 68% of samples in the cTnAAb-positive group.
IgG subclass studies confirm that cTnAAb formation may be triggered/boosted in acute cardiac events. This new information about the epitope specificity of cTnAAbs should be used to reevaluate existing recommendations regarding use of midfragment epitopes in cTnI assays. To circumvent the negative interference of the highly heterogeneous cTnAAbs, use of 3 or more unconventionally selected epitopes should be considered.
心肌肌钙蛋白（cTn）自身抗体（cTnAAbs）可干扰免疫分析法检测心肌肌钙蛋白 I（cTnI），从而导致心肌梗死的误诊。因此，我们对循环 cTnAAbs 的 cTnI 结合位点和 IgG 亚类进行了研究。
我们通过测量加入 10 份 cTnAAb 阴性和 10 份 cTnAAb 阳性的健康志愿者血清中的肌钙蛋白复合物的恢复情况，来研究表位特异性。为了研究 IgG 亚类，我们对胸痛患者的入院和 3 个月随访血清进行了分析，该分析采用参考测定法（3 个月时 14 份 cTnAAb 阴性和 14 份 cTnAAb 阳性）和 4 种亚类特异性测定法（仅测定 IgG 亚类 1-4）进行。
cTnAAb 阳性样本中单个 cTnI 表位的肌钙蛋白复合物的平均回收率范围为 37%至 211%，其中 cTnI 中间片段（aa30-110）最低。然而，最低的样本特异性回收率为 4%-92%，表明没有研究的表位完全逃脱了 cTnAAb 相关的干扰。cTnAAb 阳性组中的 8 例胸痛患者在采样点之间变为阳性，根据所有 5 种 cTnAAb 测定法，随访时的特异性信号通常更高。在 cTnAAb 阳性组中，68%的样本中检测到 IgG4，其检出率最高。
IgG 亚类研究证实，cTnAAb 的形成可能在急性心脏事件中被触发/增强。关于 cTnI 测定中使用中间片段表位的现有建议，应根据这些关于 cTnAAb 表位特异性的新信息进行重新评估。为了规避高度异质的 cTnAAbs 的负面干扰，应考虑使用 3 种或更多非传统选择的表位。
