An ImmunoSignature test distinguishes Trypanosoma cruzi, hepatitis B, hepatitis C and West Nile virus seropositivity among asymptomatic blood donors,PLOS Neglected Tropical Diseases

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An ImmunoSignature test distinguishes Trypanosoma cruzi, hepatitis B, hepatitis C and West Nile virus seropositivity among asymptomatic blood donors
PLOS Neglected Tropical Diseases ( IF 3.4 ) Pub Date : 2017-09-05 , DOI: 10.1371/journal.pntd.0005882
Michael Rowe ₁ , Jonathan Melnick ₁ , Robert Gerwien ₁ , Joseph B Legutki ₂ , Jessica Pfeilsticker ₁ , Theodore M Tarasow ₁ , Kathryn F Sykes ₂

Affiliation

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：

免疫签名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

真核寄生虫克氏锥虫(Trypanosoma (T. ) cruzi)的复杂性体现在其高度动态的基因组、多宿主生命周期、渐进的形态和免疫逃避机制。准确确定感染或恰加斯病的活动性和预后仍然是研究人员面临的挑战。我们假设比以前使用的配体复杂性更高的诊断平台可能具有价值。

方法论

我们应用免疫特征技术 (IST) 来检测T 。健康献血者中存在克鲁兹特异性抗体。 IST 的基础是通过将个体的外周血暴露于 >100,000 个位置可寻址、化学多样性肽库中来捕获个体抗体库中的信息。

主要发现

最初，对来自银行检测呈阳性或阴性的两个恰加斯人群的样本进行了研究。在第一组中，文库肽显示出T之间的差异结合信号。 cruzi血清状态用于训练算法。固定分类器并针对独立于训练的第二组进行测试以确定分析性能。接下来，来自宣布查加斯病毒、乙型肝炎、丙型肝炎或西尼罗河病毒呈阳性的混合捐赠者群体的样本在同一个库中进行了分析。信号被用来训练区分所有四种疾病状态的单一算法。作为二进制测试，预测T的准确性。与传统 ELISA 相比，IST 检测的cruzi血清阳性率相似，或许略有降低。然而，结果表明可能已经捕获了超出血清阳性测定范围的信息。其中包括队列亚类的识别、其他疾病的同时检测和辨别以及推定的新抗原的发现。