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首页> 外文期刊>EBioMedicine >Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field
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Application of new host biomarker profiles in quantitative point-of-care tests facilitates leprosy diagnosis in the field

机译:新宿主生物标志物概况在定量的定期检测中的应用有助于在该领域进行麻风病诊断

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Background Transmission of Mycobacterium leprae , the pathogen causing leprosy, is still persistent. To facilitate timely (prophylactic) treatment and reduce transmission it is vital to both early diagnose leprosy, and identify infected individuals lacking clinical symptoms. However, leprosy-specific biomarkers are limited, particularly for paucibacillary disease. Therefore, our objective was to identify new biomarkers for leprosy and assess their applicability in point-of-care (POC) tests. Methods Using multiplex-bead-arrays, 60 host-proteins were measured in a cross-sectional approach in 24-h whole blood assays (WBAs) collected in Bangladesh (79 patients; 54 contacts; 51 endemic controls (EC)). Next, 17 promising biomarkers were validated in WBAs of a separate cohort (55 patients; 27 EC). Finally, in a third cohort (36 patients; 20 EC), five candidate markers detectable in plasma were assessed for application in POC tests. Findings This study identified three new biomarkers for leprosy (ApoA1, IL-1Ra, S100A12), and confirmed five previously described biomarkers (CCL4, CRP, IL-10, IP-10, αPGL-I IgM). Overnight stimulation in WBAs provided increased specificity for leprosy and was required for IL-10, IL-1Ra and CCL4. The remaining five biomarkers were directly detectable in plasma, hence suitable for rapid POC tests. Indeed, lateral flow assays (LFAs) utilizing this five-marker profile detected both multi- and paucibacillary leprosy patients with variable immune responses. Interpretation Application of novel host-biomarker profiles to rapid, quantitative LFAs improves leprosy diagnosis and allows POC testing in low-resource settings. This platform can thus aid diagnosis and classification of leprosy and also provides a tool to detect M.leprae infection in large-scale contact screening in the field.
机译:背景传播细胞分枝杆菌,导致麻风病的病原体仍然存在。为了促进及时(预防性)治疗和降低传播,对早期诊断麻风病,并且鉴定缺乏临床症状的感染个体至关重要。然而,对皮麻素的生物标志物有限,特别是对于白细胞疾病。因此,我们的目标是识别麻风病的新生物标志物,并评估他们在护理点(POC)测试中的适用性。使用多重珠子阵列的方法,以孟加拉国收集的24-H全血检(WBA)的横截面方法测量60个宿主蛋白(79例患者; 54个触点; 51个地方控制(EC))。接下来,在单独的队列(55例患者; 27欧共体)的WBA中验证了17名有前途的生物标志物。最后,在第三个队列(36例患者; 20例)中,评估在POC试验中施用血浆中检测到的五种候选标记。结果该研究确定了一种Leprosy(ApoA1,IL-1RA,S100A12)的三种新的生物标志物,并确认了五个先前描述的生物标志物(CCL4,CRP,IL-10,IP-10,αpGL-I IgM)。 WBA的过夜刺激为麻风病提供了增加的特异性,并且是IL-10,IL-1RA和CCL4所需的。剩余的五个生物标志物在等离子体中直接可检测到,因此适用于快速的POC测试。实际上,利用该五个标记轮廓的横向流动测定(LFA)检测到具有可变免疫应答的多次生和白细胞的麻风病患者。新型宿主生物标志物谱对快速,定量LFA的解释应用改善了麻风病诊断,允许在低资源设置中进行POC测试。因此,该平台可以帮助Leprosy的诊断和分类,并提供一种在该领域的大规模接触筛选中检测M.Leprae感染的工具。

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