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对林氏曼蚊 LinB-13 的血清转化可作为皮肤利什曼病发病的生物标志物。

Seroconversion to Lutzomyia intermedia LinB-13 as a biomarker for developing cutaneous leishmaniasis.

机构信息

Instituto Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, 40296-710, Brazil.

Postgraduate Program in Health Sciences, Federal University of Bahia, School of Medicine, Salvador, Brazil.

出版信息

Sci Rep. 2017 Jun 9;7(1):3149. doi: 10.1038/s41598-017-03345-0.

Abstract

Sand flies inject saliva while feeding in the vertebrate host and anti-saliva antibodies can be used as biomarkers of exposure to Leishmania vectors. We expressed recombinant salivary proteins from Lutzomyia intermedia, a vector of Leishmania braziliensis, and evaluated the seroreactivity in exposed individuals in search for exposure markers. We found a strong correlation among positive serology to recombinant proteins LinB-13, 26, 15, 21 and to salivary proteins: rLinB-13 was the top performing molecule; IgG4 was the most predominant antibody subclass and antibodies to rLinB-13 did not cross react with Lu. longipalpis salivary proteins. By evaluating a cohort of contacts of CL patients, we confirmed that rLinB-13, an antigen 5-related protein, is a marker of exposure to Lu. intermedia with high degree of accuracy. In a 5-year follow up, we determined that individuals who developed CL presented higher anti-rLinB13 IgG responses, before the appearance of clinical symptoms. They also presented a lower frequency of cellular responses to the parasite (DTH). Our results show that seroconversion to a salivary molecule, rLinB-13, is a marker of risk for CL development caused by Leishmania braziliensis. This highlight the possibility of developing tools based on vector molecules to manage the disease in endemic areas.

摘要

沙蝇在吸食脊椎动物宿主时会注入唾液,抗唾液抗体可用作暴露于利什曼原虫媒介的生物标志物。我们从中间白蛉属(Lutzomyia intermedia)表达了重组唾液蛋白,该种是巴西利什曼原虫的传播媒介,并评估了暴露个体中的血清反应性,以寻找暴露标志物。我们发现重组蛋白 LinB-13、26、15、21 与唾液蛋白之间的血清学反应呈强相关性:rLinB-13 是表现最佳的分子;IgG4 是最主要的抗体亚类,并且针对 rLinB-13 的抗体不会与 Lu. longipalpis 唾液蛋白发生交叉反应。通过评估一组 CL 患者的接触者,我们证实 rLinB-13(一种抗原 5 相关蛋白)是 Lu. intermedia 暴露的高度准确的标志物。在 5 年的随访中,我们确定了那些发展为 CL 的个体在出现临床症状之前,针对 rLinB13 的 IgG 反应更高。他们对寄生虫(DTH)的细胞反应频率也更低。我们的结果表明,针对唾液分子 rLinB-13 的血清转化是由巴西利什曼原虫引起的 CL 发展的风险标志物。这突出了基于媒介分子开发工具来管理流行地区疾病的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6195/5466628/7022d95710c4/41598_2017_3345_Fig1_HTML.jpg

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