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ChimLeish,一种新的重组嵌合蛋白,作为内脏利什曼病和人类免疫缺陷病毒合并感染的诊断和预后标志物进行评估。

ChimLeish, a new recombinant chimeric protein evaluated as a diagnostic and prognostic marker for visceral leishmaniasis and human immunodeficiency virus coinfection.

机构信息

Laboratório de Pesquisa do Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Avenida Prof. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil.

Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 88806-000, Brazil.

出版信息

Parasitol Res. 2021 Dec;120(12):4037-4047. doi: 10.1007/s00436-021-07342-1. Epub 2021 Oct 19.

DOI:10.1007/s00436-021-07342-1
PMID:34664113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8523347/
Abstract

Visceral leishmaniasis (VL) is a neglected tropical disease of global importance caused by parasites of the genus Leishmania, and coinfection with human immunodeficiency virus (HIV) is common in countries where both diseases are endemic. In particular, widely used immunological tests for VL diagnosis have impaired sensitivity (Se) and specificity (Sp) in VL/HIV coinfected patients and there is also cross-reactivity with other endemic diseases, e.g., Chagas disease, malaria, and tuberculosis. To develop new antigens to improve the diagnosis of VL and VL/HIV coinfection, we predicted eight specific B-cell epitopes of four Leishmania infantum antigens and constructed a recombinant polypeptide chimera antigen called ChimLeish. A serological panel of 195 serum samples was used to compare the diagnostic capabilities of ChimLeish alongside the individual synthetic peptides. ChimLeish reacted with sera from all VL and VL/HIV coinfected patients [Se = 100%; Sp = 100%; area under the curve (AUC) = 1.0]. Peptides showed lower reactivities (Se = 76.8 to 99.2%; Sp = 67.1 to 95.7%; AUC between 0.87 and 0.98) as did a L. infantum antigenic preparation used as an antigen control (Se = 56.8%; Sp = 69.5%: AUC = 0.45). Notably, ChimLeish demonstrated a significant reduction (p < 0.05) of anti-ChimLeish antibodies after treatment and cure of a small number of patients. Although only a limited serological panel was tested, preliminary data suggest that ChimLeish should be evaluated in larger sample studies for the diagnosis of VL and VL/HIV coinfection.

摘要

内脏利什曼病(VL)是一种具有全球重要性的被忽视的热带病,由利什曼原虫属寄生虫引起,在同时流行这两种疾病的国家,人类免疫缺陷病毒(HIV)合并感染很常见。特别是,用于 VL 诊断的广泛使用的免疫学检测在 VL/HIV 合并感染患者中具有受损的敏感性(Se)和特异性(Sp),并且与其他地方性疾病(例如,恰加斯病、疟疾和结核病)也存在交叉反应。为了开发新的抗原以改善 VL 和 VL/HIV 合并感染的诊断,我们预测了四种利什曼原虫婴儿抗原的八个特定 B 细胞表位,并构建了一种称为 ChimLeish 的重组多肽嵌合抗原。使用 195 份血清样本的血清学小组来比较 ChimLeish 与单个合成肽的诊断能力。ChimLeish 与所有 VL 和 VL/HIV 合并感染患者的血清发生反应[Se = 100%;Sp = 100%;曲线下面积(AUC)= 1.0]。肽的反应性较低(Se = 76.8 至 99.2%;Sp = 67.1 至 95.7%;AUC 在 0.87 至 0.98 之间),用作抗原对照的利什曼原虫抗原制剂也是如此(Se = 56.8%;Sp = 69.5%:AUC = 0.45)。值得注意的是,在少数患者接受治疗和治愈后,ChimLeish 显示抗 ChimLeish 抗体显著减少(p <0.05)。尽管仅测试了有限的血清学小组,但初步数据表明,ChimLeish 应该在更大的样本研究中评估用于诊断 VL 和 VL/HIV 合并感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/a5adb361ead6/436_2021_7342_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/e732f6fc9806/436_2021_7342_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/032c4a317613/436_2021_7342_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/0cf21fd6f4ff/436_2021_7342_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/a5adb361ead6/436_2021_7342_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/e732f6fc9806/436_2021_7342_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/032c4a317613/436_2021_7342_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/0cf21fd6f4ff/436_2021_7342_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4146/8523347/a5adb361ead6/436_2021_7342_Fig4_HTML.jpg

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