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抗真菌药物甲硫氨酸合成酶抗体在系统性念珠菌病中的诊断、预后和危险分层的可靠性:蛋白质组学标志物原型开发阶段的通用策略。

Reliability of antibodies to Candida methionine synthase for diagnosis, prognosis and risk stratification in systemic candidiasis: A generic strategy for the prototype development phase of proteomic markers.

机构信息

Department of Microbiology II, Faculty of Pharmacy, Complutense University of Madrid, Madrid, Spain.

出版信息

Proteomics Clin Appl. 2007 Oct;1(10):1221-42. doi: 10.1002/prca.200601036. Epub 2007 Sep 24.

Abstract

To be able to diagnose systemic candidiasis (SC) and to predict outcomes in SC patients are still challenging tasks for physicians. Previous proteomic studies suggest that anti-Candida methionine synthase (Met6p) IgG antibodies may be a candidate marker for SC. To evaluate their reliability for diagnosis, prognosis and risk stratification in SC, we developed a generic prototype strategy for their measurement in SC. Receiver-operating-characteristic curve analyses revealed a high diagnostic accuracy for this prototype format, which was slightly better to that for the widely used Western blot assays. Multivariate logistic-regression models showed a positive association between serum anti-Met6p IgG antibody levels and SC risk that was independent from established SC risk factors and other baseline variables. After adjusting for and stratifying according to known prognostic factors, a significant trend toward a lower two-month mortality risk with increasing levels was evidenced in SC patients at presentation. We conclude that these antibodies may be useful in discriminating SC from non-SC patients and determining risk stratification in SC. These may also confer protection against SC and be valuable for the design of future immunotherapies. Furthermore, our prototype format has the potential to make impact on other infectious diseases, cancers, allergies or autoimmune disorders.

摘要

能够诊断系统性念珠菌病(SC)并预测 SC 患者的结局仍然是医生面临的挑战。先前的蛋白质组学研究表明,抗念珠菌甲硫氨酸合酶(Met6p)IgG 抗体可能是 SC 的候选标志物。为了评估其在 SC 中的诊断、预后和风险分层的可靠性,我们开发了一种用于 SC 中测量的通用原型策略。受试者工作特征曲线分析显示,该原型格式具有较高的诊断准确性,略优于广泛使用的 Western blot 检测方法。多变量逻辑回归模型显示,血清抗 Met6p IgG 抗体水平与 SC 风险之间存在正相关,这种相关性独立于已建立的 SC 危险因素和其他基线变量。在调整和分层考虑已知的预后因素后,在就诊时的 SC 患者中,随着水平的升高,其两个月死亡率的风险呈显著下降趋势。我们得出结论,这些抗体可用于区分 SC 患者和非 SC 患者,并确定 SC 的风险分层。这些抗体可能对 SC 具有保护作用,对未来的免疫治疗具有重要价值。此外,我们的原型格式有可能对其他传染病、癌症、过敏或自身免疫性疾病产生影响。

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