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通过免疫蛋白质组学分析鉴定日本血吸虫成虫排泄物/分泌物中诱导短暂抗体应答的蛋白质。

Identification of proteins inducing short-lived antibody responses from excreted/secretory products of Schistosoma japonicum adult worms by immunoproteomic analysis.

机构信息

Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Wuxi 214064, People's Republic of China.

出版信息

J Proteomics. 2013 Jul 11;87:53-67. doi: 10.1016/j.jprot.2013.05.003. Epub 2013 May 16.

Abstract

UNLABELLED

The excretory/secretory antigens of Schistosoma japonicum (Sj ESAgs) play important roles in host-parasite immune interactions. In this study, the antibody response patterns to Sj ESAgs in sera of individual rabbits at the healthy stage, 2-6 weeks post-infection and 4-16 weeks after treatment were examined. Antigens inducing short-lived antibody responses were selected by comparing differences in immune recognition of proteins in sera across the different stages by Western blotting and identified by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS). The diagnostic value of these short-lived antibody responses for schistosomiasis was investigated. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as a major antigen inducing a short-lived antibody response in Sj ESAgs. The antibody response against Sj GAPDH decreased at week 4 and disappeared between weeks 8-12 after effective chemical treatment of rabbits, and this response declined to negative levels in schistosomiasis patients one year after treatment. The intensity of the antibody response against Sj GAPDH was dependent on parasite load in mice. The sensitivity and specificity of IgG antibodies against recombinant Sj GAPDH for schistosomiasis diagnosis were 82.5% and 91.3%. Our findings suggest that Sj GAPDH induces short-lived antibody responses in the host, and detecting IgG against this antigen provides the basis for developing a potential method for diagnosis and evaluating treatment effects for schistosomiasis japonicum.

BIOLOGICAL SIGNIFICANCE

Schistosomiasis is one of the world's major public health problems. Developing effective diagnostic methods for detecting schistosome-specific antibodies to effectively identify active infections is part of a critical strategy for blocking transmission of the parasite and eradicating schistosomiasis. The excretory/secretory antigens of S. japonicum (Sj ESAgs) play important roles in host-parasite immune interactions. In our study, we examine the antibody response patterns to Sj ESAgs within individual rabbits at the healthy, schistosome infection and post-treatment stages by Western blotting. Proteins among the Sj ESAgs inducing short-lived antibody responses were identified by Matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), and their potential as immune markers for diagnosis and evaluating therapeutic effects in schistosomiasis was evaluated. Our findings suggest that S. japonicum glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces short-lived antibody responses in the host, and detecting IgG against this antigen provides the basis for developing a potential method for diagnosis and evaluating treatment effects for schistosomiasis japonicum.

摘要

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日本血吸虫(Sj ESAgs)的排泄/分泌抗原在宿主-寄生虫免疫相互作用中发挥重要作用。在这项研究中,通过 Western blot 比较了健康期、感染后 2-6 周和治疗后 4-16 周个体兔血清中 Sj ESAgs 的抗体反应模式。通过基质辅助激光解吸/电离串联飞行时间质谱(MALDI-TOF/TOF-MS)比较不同阶段血清中蛋白质的免疫识别差异,选择诱导短暂抗体反应的抗原,并对其进行鉴定。研究了这些短暂抗体反应对血吸虫病的诊断价值。己糖醛酸-3-磷酸脱氢酶(GAPDH)被鉴定为 Sj ESAgs 中诱导短暂抗体反应的主要抗原。感染后第 4 周,兔血清中针对 Sj GAPDH 的抗体反应下降,经有效化学治疗后第 8-12 周消失,治疗 1 年后血吸虫病患者的抗体反应降至阴性水平。针对 Sj GAPDH 的抗体反应强度与小鼠体内的寄生虫负荷有关。针对重组 Sj GAPDH 的 IgG 抗体对血吸虫病诊断的灵敏度和特异性分别为 82.5%和 91.3%。我们的研究结果表明,日本血吸虫 GAPDH 诱导宿主产生短暂的抗体反应,检测针对该抗原的 IgG 可为开发潜在的血吸虫病诊断方法和评估治疗效果提供依据。

生物学意义

血吸虫病是全球主要公共卫生问题之一。开发有效的检测方法来有效识别针对血吸虫的特异性抗体,以有效识别活动性感染,是阻断寄生虫传播和消灭血吸虫病的关键策略的一部分。日本血吸虫(Sj ESAgs)的排泄/分泌抗原在宿主-寄生虫免疫相互作用中发挥重要作用。在我们的研究中,我们通过 Western blot 检测了健康期、感染期和治疗后个体兔血清中的 Sj ESAgs 抗体反应模式。通过基质辅助激光解吸/电离串联飞行时间质谱(MALDI-TOF/TOF-MS)鉴定 Sj ESAgs 中诱导短暂抗体反应的蛋白质,并评估其作为血吸虫病诊断和评估治疗效果的免疫标志物的潜力。我们的研究结果表明,日本血吸虫己糖醛酸-3-磷酸脱氢酶(GAPDH)诱导宿主产生短暂的抗体反应,检测针对该抗原的 IgG 为开发潜在的日本血吸虫病诊断和评估治疗效果的方法提供了依据。

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