Steingart Karen R, Dendukuri Nandini, Henry Megan, Schiller Ian, Nahid Payam, Hopewell Philip C, Ramsay Andrew, Pai Madhukar, Laal Suman
Francis J. Curry National Tuberculosis Center, University of California, San Francisco, 3180 18th Street, Suite 101, San Francisco, CA 94110-2028, USA.
Clin Vaccine Immunol. 2009 Feb;16(2):260-76. doi: 10.1128/CVI.00355-08. Epub 2008 Dec 3.
Serological antibody detection tests for tuberculosis may offer the potential to improve diagnosis. Recent meta-analyses have shown that commercially available tests have variable accuracies and a limited clinical role. We reviewed the immunodiagnostic potential of antigens evaluated in research laboratories (in-house) for the serodiagnosis of pulmonary tuberculosis and conducted a meta-analysis to evaluate the performance of comparable antigens. Selection criteria included the participation of at least 25 pulmonary tuberculosis patients and the use of purified antigens. Studies evaluating 38 kDa, MPT51, malate synthase, culture filtrate protein 10, TbF6, antigen 85B, alpha-crystallin, 2,3-diacyltrehalose, 2,3,6-triacyltrehalose, 2,3,6,6'-tetraacyltrehalose 2'-sulfate, cord factor, and TbF6 plus DPEP (multiple antigen) were included in the meta-analysis. The results demonstrated that (i) in sputum smear-positive patients, sensitivities significantly >or=50% were provided for recombinant malate synthase (73%; 95% confidence interval [CI], 58 to 85) and TbF6 plus DPEP (75%; 95% CI, 50 to 91); (ii) protein antigens achieved high specificities; (iii) among the lipid antigens, cord factor had the best overall performance (sensitivity, 69% [95% CI, 28 to 94]; specificity, 91% [95% CI, 78 to 97]); (iv) compared with the sensitivities achieved with single antigens (median sensitivity, 53%; range, 2% to 100%), multiple antigens yielded higher sensitivities (median sensitivity, 76%; range, 16% to 96%); (v) in human immunodeficiency virus (HIV)-infected patients who are sputum smear positive, antibodies to several single and multiple antigens were detected; and (vi) data on seroreactivity to antigens in sputum smear-negative or pediatric patients were insufficient. Potential candidate antigens for an antibody detection test for pulmonary tuberculosis in HIV-infected and -uninfected patients have been identified, although no antigen achieves sufficient sensitivity to replace sputum smear microscopy. Combinations of select antigens provide higher sensitivities than single antigens. The use of a case-control design with healthy controls for the majority of studies was a limitation of the review. Efforts are needed to improve the methodological quality of tuberculosis diagnostic studies.
结核病的血清学抗体检测试验可能具有改善诊断的潜力。最近的荟萃分析表明，市售检测方法的准确性各不相同，临床作用有限。我们回顾了研究实验室（内部）评估的抗原在肺结核血清诊断中的免疫诊断潜力，并进行了一项荟萃分析以评估可比抗原的性能。选择标准包括至少25名肺结核患者的参与以及使用纯化抗原。评估38 kDa、MPT51、苹果酸合酶、培养滤液蛋白10、TbF6、抗原85B、α-晶状体蛋白、2,3-二酰基海藻糖、2,3,6-三酰基海藻糖、2,3,6,6'-四酰基海藻糖2'-硫酸盐、索状因子以及TbF6加DPEP（多种抗原）的研究纳入了荟萃分析。结果表明：（i）在痰涂片阳性患者中，重组苹果酸合酶（73%；95%置信区间[CI]，58至85）和TbF6加DPEP（75%；95%CI，50至91）的敏感性显著≥50%；（ii）蛋白质抗原具有高特异性；（iii）在脂质抗原中，索状因子的总体性能最佳（敏感性，69%[95%CI，28至94]；特异性，91%[95%CI，78至97]）；（iv）与单一抗原的敏感性（中位敏感性，53%；范围，2%至100%）相比，多种抗原产生更高的敏感性（中位敏感性，76%；范围，16%至96%）；（v）在痰涂片阳性的人类免疫缺陷病毒（HIV）感染患者中，检测到了针对几种单一和多种抗原的抗体；（vi）关于痰涂片阴性或儿科患者对抗原的血清反应性的数据不足。已确定了HIV感染和未感染患者肺结核抗体检测试验的潜在候选抗原，尽管没有一种抗原具有足够的敏感性来取代痰涂片显微镜检查。选择的抗原组合比单一抗原具有更高的敏感性。大多数研究采用健康对照的病例对照设计是该综述的一个局限性。需要努力提高结核病诊断研究的方法学质量。
