Lage Daniela P, Martins Vívian T, Duarte Mariana C, Costa Lourena E, Garde Esther, Dimer Laura M, Kursancew Amanda C S, Chávez-Fumagalli Miguel A, de Magalhães-Soares Danielle F, Menezes-Souza Daniel, Roatt Bruno M, Machado-de-Ávila Ricardo A, Soto Manuel, Tavares Carlos A P, Coelho Eduardo A F
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.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.
Parasitol Res. 2016 Apr;115(4):1649-58. doi: 10.1007/s00436-016-4904-x. Epub 2016 Jan 19.
The serodiagnosis of canine visceral leishmaniasis (CVL) presents problems related to its sensitivity and/or specificity. In the present study, a new Leishmania-specific hypothetical protein, LiHyD, was produced as a recombinant protein (rLiHyD) and evaluated in ELISA experiments for the CVL serodiagnosis. LiHyD was characterized as antigenic in a recent immunoproteomic search performed with Leishmania infantum proteins and the sera of dogs developing visceral leishmaniasis (VL). Aiming to compare the efficacy between whole proteins and synthetic peptides, two linear and one conformational B cell epitopes of LiHyD were synthesized and also evaluated as diagnostic markers. The four antigens were recognized by the sera of dogs suffering VL. On the contrary, low reactivity was observed when they were assayed with sera from non-infected healthy dogs living in endemic or non-endemic areas of leishmaniasis. In addition, no reactivity was found against them using sera from dogs experimentally infected by Trypanosoma cruzi, Babesia canis, or Ehrlichia canis, or sera from animals vaccinated with the Leish-Tec® vaccine, a prophylactic preparation commercially available for CVL prevention in Brazil. As comparative diagnostic tools, a recombinant version of the amastigote-specific A2 protein and a soluble crude Leishmania extract were studied. Both antigens presented lower sensitivity and/or specificity values than the LiHyD-based products. The rLiHyD presented better results for the CVL serodiagnosis than its linear epitopes, although the peptide recreating the conformational epitope resulted also appropriate as a diagnostic marker of CVL. To the best of our knowledge, this is the first study showing the use of a conformational epitope derived from a Leishmania protein for serodiagnosis of CVL.
犬内脏利什曼病(CVL)的血清学诊断存在与其敏感性和/或特异性相关的问题。在本研究中,一种新的利什曼原虫特异性假设蛋白LiHyD被制备为重组蛋白(rLiHyD),并在ELISA实验中用于CVL的血清学诊断评估。在最近一项用婴儿利什曼原虫蛋白和患内脏利什曼病(VL)犬血清进行的免疫蛋白质组学研究中,LiHyD被鉴定为具有抗原性。为了比较全蛋白和合成肽之间的效力,合成了LiHyD的两个线性和一个构象性B细胞表位,并也将其评估为诊断标志物。这四种抗原均能被患VL犬的血清识别。相反,用生活在利什曼病流行或非流行地区的未感染健康犬的血清检测时,观察到它们的反应性较低。此外,用经克氏锥虫、犬巴贝斯虫或犬埃立克体实验感染犬的血清,或用Leish-Tec®疫苗(巴西一种用于预防CVL的市售预防性制剂)免疫动物的血清检测时,未发现针对它们的反应性。作为比较诊断工具,研究了无鞭毛体特异性A2蛋白的重组形式和可溶性利什曼原虫粗提物。这两种抗原的敏感性和/或特异性值均低于基于LiHyD的产品。rLiHyD在CVL血清学诊断中比其线性表位表现出更好的结果,尽管重现构象表位的肽也适合作为CVL的诊断标志物。据我们所知,这是第一项展示使用源自利什曼原虫蛋白的构象表位进行CVL血清学诊断的研究。