能准确检测肺结核的尿检
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By LabMedica International staff writers Posted on 26 Jan 2018 |
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图片：纳米笼的内/外表面积比高，结合能力强。共价固定在笼内的亲合配体与结核(TB)抗原建立起高亲合度非共价相互作用（图片蒙乔治梅森大学惠赐）。
未共感染人类免疫缺陷病毒(HIV)的患者急需活跃肺结核(TB)的准确筛查检验。结核是世界上最流行的细菌感染之一，发展中国家的死亡率最高。
理想情况下，这样的检验使用尿液这样的无创体液，以适应资源不足的场合。这一目标第一眼看上去很简单，因为活跃肺结核发作期间排到尿液里的一种结核抗原——外表面的脂阿拉伯甘露糖(LAM)已得到鉴定，性质明确。
一组来自多国的科学家与美国弗吉尼亚州马那萨斯市乔治梅森大学的科学家合作，在一个水凝胶纳米笼内使用称为RB221的铜复合物染色剂，纳米笼以极高的亲合力捕获LAM，去除尿蛋白的干扰。应用该技术研究48名秘鲁患者经过预处理的尿液，全部样本都呈HIV阴性，通过金胺染色检测痰液中的抗酸杆菌，并用显微镜观察药物敏感性(MODS)测定，证实有活跃肺结核。分析前用德国埃施伯恩市西门子医疗集团诊断部的Multistix GP尿检浸量尺确定病人尿样的性质。
科学家发现，RB221纳米笼捕获了尿液里的LAM，把检测灵敏度提高了100到1,000倍，事先都排除了样本中可能干扰结果的干扰性复合物。48名HIV阴性的结核患者还未接受治疗，新检验方法检测感染的灵敏度大于95%，特异性大于80%。如果尿液中LAM的浓度范围是14到2,000皮克/毫升，与同龄的健康对照者和有病但非结核的对照者比较，就可定量测量其浓度。
尿液中LAM浓度的升高与细菌量增多以及更严重的疾病（以体重减轻或咳嗽为指标）有关。科研小组还制作了一些纳米笼，捕获和检测感染的其它标志物，包括名为6千道尔顿早期分泌性抗原靶体(ESAT6)和10千道尔顿培养滤液蛋白(CFP10)的极低浓度的分子。记录用ESAT6夹心免疫测定和侧流免疫测定检验临床样本的可行性。该研究的论文发表于2017年12月13日的《科学》杂志《转化医学》分册。作者称，他们下一步将比较患者治疗前和治疗后尿液中LAM的水平，以评估治疗可能带来的变化。
乔治梅森大学
西门子医疗集团诊断部
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