PDF(Pubmed)
Abstract：
Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus Babesia. Babesia microti is responsible for most cases of human babesiosis in the United States, particularly in the Northeast and the Upper Midwest. Babesia microti is primarily transmitted to humans through the bite of infected deer ticks but also through the transfusion of blood components, particularly red blood cells. There is a high risk of severe and even fatal disease in immunocompromised patients. To date, serology testing relies on an indirect immunofluorescence assay that uses the whole Babesia microti antigen. Here, we report the construction of phage display cDNA libraries from Babesia microti-infected erythrocytes as well as human reticulocytes obtained from donors with hereditary hemochromatosis. Plasma samples were obtained from patients who were or had been infected with Babesia microti. The non-specific antibody reactivity of these plasma samples was minimized by pre-exposure to the human reticulocyte library. Using this novel experimental strategy, immunoreactive segments were identified in three Babesia microti antigens termed BmSA1 (also called BMN1-9; BmGPI12), BMN1-20 (BMN1-17; Bm32), and BM4.12 (N1-15). Moreover, our findings indicate that the major immunoreactive segment of BmSA1 does not overlap with the segment that mediates BmSA1 binding to mature erythrocytes. When used in combination, the three immunoreactive segments form the basis of a sensitive and comprehensive diagnostic immunoassay for human babesiosis, with implications for vaccine development.
摘要：
人类巴贝斯虫病是由巴贝斯虫属的原生动物寄生虫引起的疟疾样疾病。在美国，小巴贝斯虫是大多数人类巴贝斯虫病的原因，特别是在东北部和中西部。微巴贝虫主要通过被感染的鹿蜱叮咬传播给人类，也通过输血血液成分传播给人类，尤其是红细胞。在免疫功能低下的患者中存在严重甚至致命疾病的高风险。迄今为止,血清学检测依赖于间接免疫荧光测定法，该测定法使用整个微抗体巴贝斯虫抗原。这里,我们报道了从微感染的Babesia感染的红细胞以及从遗传性血色素沉着病供体获得的人网织红细胞的噬菌体展示cDNA文库的构建。血浆样品是从感染或已经感染微巴贝虫的患者获得的。这些血浆样品的非特异性抗体反应性通过预先暴露于人网织红细胞文库而最小化。使用这种新颖的实验策略，在三种称为BmSA1（也称为BMN1-9；BmGPI12）的微巴贝虫抗原中鉴定出免疫反应性片段，BMN1-20(BMN1-17;Bm32),和BM4.12（N1-15）。此外，我们的发现表明，BmSA1的主要免疫反应片段与介导BmSA1与成熟红细胞结合的片段不重叠。当组合使用时，这三个免疫反应性片段构成了人类巴贝斯虫病灵敏而全面的诊断免疫测定的基础，对疫苗开发有影响。
