Virus-like Particle Display of the α-Gal Epitope for the Diagnostic Assessment of Chagas Disease

Virus-like Particle Display of the α-Gal Epitope for the Diagnostic Assessment of Chagas Disease
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DOI:
10.1021/acsinfecdis.6b00114
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发表时间:
2016-12-01
影响因子:
5.3
通讯作者:
Marques, Alexandre Ferreira
Marques, Alexandre Ferreira
中科院分区:
医学2区
文献类型:
--
作者:
Nascimento Brito, Carlos Ramon;Mckay, Craig S.;Marques, Alexandre Ferreira

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α-半乳糖抗原[Galα(1,3)Gal beta(1,4)GlcNAcα]是查加斯病的病原体克氏锥虫的感染性锥虫所表现的免疫优势表位。一种病毒样颗粒显示高密度的α-Gal被发现是基于ELISA的恰加斯病血清学诊断和治疗效果评估的一种优越的试剂。一组来自慢性感染旋毛虫患者的血清,无论是未经治疗的还是接受苯硝唑治疗的,都与利什曼病患者和健康捐赠者的血清进行了比较。纳米颗粒-α-半乳糖结构允许查加斯患者和其他患者之间的完美区分,避免了用当前最先进的试剂获得的假阴性和假阳性结果。正如之前报道的含有α-半乳糖的糖基磷脂酰肌醇锚定粘蛋白一样,目前的研究还显示,接受苯硝唑治疗的患者中,抗-α-半乳糖抗体的浓度显著降低,这表明对这种高度丰富的抗体的血清水平的半定量评估可以报告个别患者的疾病状况。
The alpha-Gal antigen [Gal alpha(1,3)Gal beta(1,4)GlcNAc alpha] is an immunodominant epitope displayed by infective trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. A virus-like particle displaying a high density of alpha-Gal was found to be a superior reagent for the ELISA-based serological diagnosis of Chagas disease and the assessment of treatment effectiveness. A panel of sera from patients chronically infected with T. cruzi, both untreated and benznidazole-treated, was compared with sera from patients with leishmaniasis and from healthy donors. The nanoparticle-alpha-Gal construct allowed for perfect discrimination between Chagas patients and the others, avoiding false negative and false positive results obtained with current state-of-the-art reagents. As previously reported with purified alpha-Gal-containing glycosylphosphatidylinositol-anchored mucins, the current study also showed concentrations of anti-alpha-Gal IgG to decrease substantially in patients receiving treatment with benznidazole, suggesting that the semiquantitative assessment of serum levels of this highly abundant type of antibody can report on disease status in individual patients.