Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease
Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease
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DOI：
10.1128/jcm.02111-15
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发表时间：
2015-12-01
影响因子：
9.4
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
--
作者：
Lahey, Lauren J.;Panas, Michael W.;Robinson, William H.
目前在美国莱姆病的实验室诊断标准是针对伯氏疏螺旋体抗体的血清学检测。疾病控制和预防中心建议采用两级检测算法;然而，该方案对检测早期莱姆病的敏感性有限。因此，需要在抗生素治疗非常有效的早期阶段改进莱姆病的诊断。我们检查了新的和已建立的抗原标志物，以开发一种多重面板，该面板使用多种标志物的组合灵敏度来识别早期感染，同时通过要求两种标志物的阳性结果来指定阳性检测来保持高特异性。从我们对62个B的初步分析中选择了10个标记。通过评估IgG和IgM与莱姆病患者样品和对照的训练组中的每一种的结合，测定了莱姆病表面蛋白和合成肽的结合。在一个验证集中，这个10抗原组在基线或治疗后访视时确定的早期莱姆病患者阳性比例高于两级检测（分别为87.5%和67.5%; P < 0.05）。在26名健康对照中观察到了100%的等效特异性。进一步分析后，新型10抗原组的阳性与较长的病程和多发性游走性红斑相关。在检测早期B方面，我们的10抗原组与两级检测相比，灵敏度提高，特异性相当。对莱姆病感染的研究表明，以下一代标志物为特征的多重分析可以推进诊断技术，以更好地帮助临床医生诊断和治疗早期莱姆病。
The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease.