School of Biotechnology, Dublin City University, Dublin 9 D09 V2O9, Ireland.
School of Biotechnology, Dublin City University, Dublin 9 D09 V2O9, Ireland; Qatar Foundation and Hamad Bin Khalifa University, Research Complex, Education City, Doha, Qatar.
J Immunol Methods. 2021 Oct;497:113108. doi: 10.1016/j.jim.2021.113108. Epub 2021 Jul 28.
Cardiovascular disease has remained the world's biggest killer for 30 years. To aid in the diagnosis and prognosis of patients suffering cardiovascular-related disease accurate detection methods are essential. For over 20 years, the cardiac-specific troponins, I (cTnI) and T (cTnT), have acted as sensitive and specific biomarkers to assist in the diagnosis of various types of heart diseases. Various cardiovascular complications were commonly detected in patients with COVID-19, where cTn elevation is detectable, which suggested potential prognostic value of cTn in COVID-19-infected patients. Detection of these biomarkers circulating in the bloodstream is generally facilitated by immunoassays employing cTnI- and/or cTnT-specific antibodies. While several anti-troponin assays are commercially available, there are still obstacles to overcome to achieve optimal troponin detection. Such obstacles include the proteolytic degradation of N and C terminals on cTnI, epitope occlusion of troponin binding-sites by the cTnI/cTnT complex, cross reactivity of antibodies with skeletal troponins or assay interference caused by human anti-species antibodies. Therefore, further research into multi-antibody based platforms, multi-epitope targeting and rigorous validation of immunoassays is required to ensure accurate measurements. Moreover, in combination with various technical advances (e.g. microfluidics), antibody-based troponin detection systems can be more sensitive and rapid for incorporation into portable biosensor systems to be used at point-of care.
心血管疾病 30 年来一直是世界上最大的杀手。为了帮助诊断和预测心血管疾病患者,需要准确的检测方法。20 多年来,心脏特异性肌钙蛋白 I(cTnI)和 T(cTnT)一直作为敏感和特异性生物标志物,用于辅助诊断各种类型的心脏病。在 COVID-19 患者中经常检测到各种心血管并发症,其中可检测到 cTn 升高,这表明 cTn 在 COVID-19 感染患者中有潜在的预后价值。通常通过使用 cTnI-和/或 cTnT 特异性抗体的免疫测定法来促进这些在血液中循环的生物标志物的检测。虽然有几种抗肌钙蛋白检测方法可用于商业用途,但仍需要克服一些障碍以实现最佳的肌钙蛋白检测。这些障碍包括 cTnI 的 N 和 C 末端的蛋白水解降解、cTnI/cTnT 复合物对肌钙蛋白结合位点的表位封闭、抗体与骨骼肌肌钙蛋白的交叉反应或人抗种属抗体引起的测定干扰。因此,需要进一步研究基于多抗体的平台、多表位靶向和免疫测定的严格验证,以确保准确的测量。此外,结合各种技术进步(例如微流控技术),基于抗体的肌钙蛋白检测系统可以更敏感、快速地整合到便携式生物传感器系统中,以便在床边使用。