Background

The complexity of the eukaryotic parasite Trypanosoma (T.) cruzi manifests in its highly dynamic genome, multi-host life cycle, progressive morphologies and immune-evasion mechanisms. Accurate determination of infection or Chagas’ disease activity and prognosis continues to challenge researchers. We hypothesized that a diagnostic platform with higher ligand complexity than previously employed may hold value.

Methodology

We applied the ImmunoSignature Technology (IST) for the detection of T. cruzi-specific antibodies among healthy blood donors. IST is based on capturing the information in an individual’s antibody repertoire by exposing their peripheral blood to a library of >100,000 position-addressable, chemically-diverse peptides.

Principal findings

Initially, samples from two Chagas cohorts declared positive or negative by bank testing were studied. With the first cohort, library-peptides displaying differential binding signals between T. cruzi sero-states were used to train an algorithm. A classifier was fixed and tested against the training-independent second cohort to determine assay performance. Next, samples from a mixed cohort of donors declared positive for Chagas, hepatitis B, hepatitis C or West Nile virus were assayed on the same library. Signals were used to train a single algorithm that distinguished all four disease states. As a binary test, the accuracy of predicting T. cruzi seropositivity by IST was similar, perhaps modestly reduced, relative to conventional ELISAs. However, the results indicate that information beyond determination of seropositivity may have been captured. These include the identification of cohort subclasses, the simultaneous detection and discerning of other diseases, and the discovery of putative new antigens.

Conclusions & significance

The central outcome of this study established IST as a reliable approach for specific determination of T. cruzi seropositivity versus disease-free individuals or those with other diseases. Its potential contribution for monitoring and controlling Chagas lies in IST’s delivery of higher resolution immune-state readouts than obtained with currently-used technologies. Despite the complexity of the ligand presentation and large quantitative readouts, performing an IST test is simple, scalable and reproducible.

中文翻译：

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ImmunoSignature测试可区分无症状献血者中的克氏锥虫，乙型肝炎，丙型肝炎和西尼罗河病毒血清阳性

背景

在真核寄生虫的复杂性锥虫（T。）克氏锥虫在其高度动态的基因组中，多主机的生命周期，进行性的形态和免疫逃避机制清单。准确确定感染或恰加斯病的活动和预后继续挑战研究人员。我们假设具有比以前采用的配体复杂性更高的诊断平台可能具有价值。

方法

我们将免疫签名技术（IST）应用到T的检测中。健康献血者中的cruzi特异性抗体。IST的基础是通过将个体的外周血暴露于> 100,000种可定位位置的化学多样性肽库中来捕获其抗体库中的信息。

主要发现

最初，研究了通过银行测试宣布为阳性或阴性的两个恰加斯（Chagas）队列的样本。在第一个队列中，文库肽显示了T之间的差异结合信号。使用Cruzi血清状态来训练算法。固定分类器，并针对与训练无关的第二个队列进行测试，以确定测定性能。接下来，在同一文库中对来自宣布为恰加斯，乙型肝炎，丙型肝炎或西尼罗河病毒呈阳性的混合供者的样本进行了分析。信号用于训练区分所有四种疾病状态的单一算法。作为二元检验，预测T的准确性。克鲁兹相对于常规ELISA，IST的血清阳性率相似，或有所降低。但是，结果表明，可能已经捕获了超出血清反应阳性的信息。这些包括队列同类的识别，其他疾病的同时检测和识别以及推定的新抗原的发现。

结论与意义

这项研究的主要成果将IST确立为T特异性测定的可靠方法。克鲁兹血清阳性率与无病个体或患有其他疾病的个体相比。它对南美锥虫的监测和控制的潜在贡献在于IST提供了比当前使用的技术更高分辨率的免疫状态读数。尽管配体表示复杂且定量读数大，但执行IST测试仍然简单，可扩展且可重现。