Vitta Apichat, Dekumyoy Paron, Komalamisra Chalit, Kalambaheti Thareerat, Yoshino Timothy P
Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.
Center of Excellence in Medical Biotechnology (CEMB), Naresuan University, Phitsanulok, 65000, Thailand.
Parasitol Res. 2016 Nov;115(11):4115-4122. doi: 10.1007/s00436-016-5184-1. Epub 2016 Jul 13.
Angistrongylus cantonensis is a zoonotic nematode parasite and causative agent of human angiostrongyliasis, which clinically presents as eosinophilic meningitis or meningoencephalitis. Diagnosis of the disease is problematic since parasitologic findings are infrequent, and infection determinations must be based on the clinical symptoms and serological tests with limited specificities and sensitivities. The aim of the present study was to identify and generate a novel recombinant protein from A. cantonensis and evaluate its efficacy in the diagnosis of human angiostrongyliasis when incorporated into a Western blot serodiagnostic system. A cDNA protein expression library from adult A. cantonensis was constructed, followed by immunoscreening with serum from confirmed infected patients to identify and isolate immunoreactive clones. One clone, designated fAC40, possessed a partial sequence encoding a LisH protein domain with a predicted molecular weight of 16 kDa and containing four predicted antigenic peptides. By incorporating recombinant fAC40 in Western immunoblot tests using a serum panel consisting of confirmed and clinically diagnosed cases of human angiostrongyliasis and other helminthic infections, fAC40 exhibited a sensitivity and specificity of 91.8 and 100 %, respectively, and a positive and negative predictive value of 100 and 97.19 %, respectively, in the diagnosis of angiostrongyliasis. Importantly, it was not reactive with antibodies from serum of patients infected with Gnathostoma spinigerum and Cysticercus cellulosae, infections that clinically present neurological symptoms similar to angiostrongyliasis. These data demonstrate that the 16-kDa recombinant protein from A. cantonensis possesses high potential as a candidate antigen for a more sensitive and specific serodiagnosis of human angiostrongyliasis.
广州管圆线虫是一种人兽共患的线虫寄生虫,也是人类嗜酸性粒细胞性脑膜炎或脑膜脑炎的病原体。由于寄生虫学检查结果不常见,该疾病的诊断存在问题,感染的确定必须基于临床症状以及特异性和敏感性有限的血清学检测。本研究的目的是从广州管圆线虫中鉴定并产生一种新型重组蛋白,并评估其在Western印迹血清诊断系统中用于诊断人类嗜酸性粒细胞性脑膜炎时的效果。构建了成年广州管圆线虫的cDNA蛋白表达文库,然后用确诊感染患者的血清进行免疫筛选,以鉴定和分离免疫反应性克隆。一个名为fAC40的克隆具有编码LisH蛋白结构域的部分序列,预测分子量为16 kDa,包含四个预测的抗原肽。通过将重组fAC40用于由确诊和临床诊断的人类嗜酸性粒细胞性脑膜炎病例以及其他蠕虫感染病例组成的血清样本进行Western免疫印迹试验,fAC40在嗜酸性粒细胞性脑膜炎诊断中的敏感性和特异性分别为91.8%和100%,阳性预测值和阴性预测值分别为100%和97.19%。重要的是,它与感染棘颚口线虫和猪囊尾蚴患者血清中的抗体无反应,这两种感染临床上表现出与嗜酸性粒细胞性脑膜炎相似的神经症状。这些数据表明,来自广州管圆线虫的16 kDa重组蛋白作为人类嗜酸性粒细胞性脑膜炎更敏感和特异血清诊断的候选抗原具有很高的潜力。