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载脂蛋白A1和纤连蛋白片段作为恰加斯病治愈的标志物

Apolipoprotein A1 and Fibronectin Fragments as Markers of Cure for the Chagas Disease.

作者信息

Ruiz-Lancheros Elizabeth, Golizeh Makan, Ndao Momar

机构信息

National Reference Centre for Parasitology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Program in Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

出版信息

Methods Mol Biol. 2019;1955:263-273. doi: 10.1007/978-1-4939-9148-8_20.

Abstract

Chagas disease (CD), endemic from Latin America, affects more than 8 million people, and the disease keeps spreading around the world due to population migrations. The treatment options for CD are currently limited to two drugs, benznidazole (BZ) and nifurtimox (Nfx), which are often unsatisfactory in chronically infected patients. To date, the only accepted marker of the cure is seroconversion (the disappearance of Trypanosoma cruzi antibodies in the patient's serum), which can take decades to occur, if ever. The lack of posttreatment test-of-cure often prevents appropriate patient counseling and limits the development of new drugs. Without a doubt, reliable biomarkers for parasitological cure are urgently needed. Several pieces of evidence suggest that apolipoprotein A1 and fibronectin fragments are produced during the infection as part of the process of T. cruzi cell invasion and can thus be used as its surrogate biomarkers. In this chapter, we present a standardized method to evaluate these fragments in serum using mass spectrometry and immunoblotting in CD patients for diagnosis, prognosis, and treatment assessment purposes.

摘要

恰加斯病(CD)在拉丁美洲流行,感染人数超过800万,并且由于人口迁移,该疾病在全球范围内持续传播。目前,CD的治疗选择仅限于两种药物,即苯硝唑(BZ)和硝呋替莫(Nfx),对于慢性感染患者,这两种药物的治疗效果往往不尽人意。迄今为止,唯一被认可的治愈标志物是血清学转换(患者血清中克氏锥虫抗体消失),而这可能需要数十年时间才会出现,甚至可能根本不会出现。缺乏治疗后治愈检测常常阻碍对患者进行适当的咨询,并限制了新药的研发。毫无疑问,迫切需要可靠的寄生虫学治愈生物标志物。有多项证据表明,载脂蛋白A1和纤连蛋白片段是在感染过程中作为克氏锥虫细胞入侵过程的一部分产生的,因此可作为其替代生物标志物。在本章中,我们介绍一种标准化方法,用于通过质谱分析和免疫印迹法评估CD患者血清中的这些片段,以用于诊断﹑预后和治疗评估。

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