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针对硫氧还蛋白还原酶的抗体作为一种新的生物标志物,用于诊断非中性粒细胞减少患者侵袭性曲霉菌病的血清学诊断。

Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients.

机构信息

School of Medical Technology, Jiangsu University, Zhenjiang 212013, PR China.

出版信息

Clin Chim Acta. 2012 May 18;413(9-10):938-43. doi: 10.1016/j.cca.2012.02.011. Epub 2012 Feb 17.

DOI:10.1016/j.cca.2012.02.011
PMID:22366166
Abstract

BACKGROUND

Invasive aspergillosis (IA) is an important cause of mortality in critically ill patients, but the diagnosis is difficult as clinical and radiological signs are neither sensitive nor specific. Serum galactomannan (GM) is a useful marker for IA, but exhibits low sensitivity in non-neutropenic patients. In our previous work, strong antibody reactivity to thioredoxin reductase of Aspergillus fumigatus was found in non-neutropenic IA patients.

METHODS AND RESULTS

Using recombinant thioredoxin reductase GliT (TR), an antigenic protein secreted by A. fumigatus, as the coating antigen, an enzyme-linked immunosorbent assay (ELISA) for detecting anti-TR antibodies was developed. The antibody response to TR in IA animal models and 42 non-neutropenic patients with culture- and/or histology-documented IA was investigated. The results showed that anti-TR antibody was detectable in rabbit serum 7-9 days after exposure to the fungus. The sensitivity and specificity of the anti-TR antibody assay in patients were 80.9% and 96%, respectively, while the sensitivity of GM in this group of patients was only 52.3%. The specificity of the assay was confirmed by testing the sera from patients infected with other pathogenic fungal species and bacteria.

摘要

背景

侵袭性曲霉病(IA)是危重症患者死亡的重要原因,但由于临床和影像学征象既不敏感也不特异,诊断困难。血清半乳甘露聚糖(GM)是诊断 IA 的有用标志物,但在非中性粒细胞减少症患者中的敏感性较低。在我们之前的研究中,在非中性粒细胞减少性 IA 患者中发现了对烟曲霉硫氧还蛋白还原酶的强烈抗体反应。

方法和结果

使用重组烟曲霉硫氧还蛋白还原酶 GliT(TR)作为包被抗原,该抗原是烟曲霉分泌的一种抗原蛋白,开发了一种用于检测抗 TR 抗体的酶联免疫吸附试验(ELISA)。研究了 TR 抗体在 IA 动物模型和 42 例经培养和/或组织学证实的非中性粒细胞减少性 IA 患者中的抗体反应。结果表明,暴露于真菌后 7-9 天,兔血清中可检测到抗 TR 抗体。该抗体检测方法在患者中的灵敏度和特异性分别为 80.9%和 96%,而 GM 在该组患者中的灵敏度仅为 52.3%。通过检测感染其他致病性真菌和细菌的患者的血清,证实了该检测方法的特异性。

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