Department of Sexually Transmitted Diseases, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China; Guangzhou Key Laboratory for Sexually Transmitted Diseases Control, Guangzhou, Guangdong, China.
Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China; Guangzhou Baiyun District Center for Disease Control and Prevention, Guangzhou, Guangdong, China.
Clin Microbiol Infect. 2024 Oct;30(10):1298-1304. doi: 10.1016/j.cmi.2024.06.013. Epub 2024 Jun 22.
Invasive lumbar puncture is the conventional method for diagnosing neurosyphilis (NS). We investigated a non-invasive alternative method to detect serum Treponema pallidum-specific antibodies against highly immunogenic antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) by using luciferase immunosorbent assay.
A total of 816 HIV-negative patients suspected of NS from the Beijing and Guangzhou cohorts were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibodies. Two diagnostic prediction models were developed using stepwise logistic regression in the Beijing cohort, and evaluated in the Guangzhou cohort for external validation.
Serum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in the Beijing cohort and the corresponding area under the receiver operating characteristic curves (AUCs) were 0.722 [95% confidence interval (CI): 0.680-0.762)], 0.780 (95% CI: 0.741-0.817), and 0.774 (95% CI: 0.734-0.811), respectively. An expanded NS prediction model integrated with anti-TP17 and anti-TP47 antibodies showed better performance than the base NS diagnostic model without anti-TP17 and anti-TP47 antibodies with the AUC of 0.874 (95% CI: 0.841-0.906) vs. 0.845 (95% CI: 0.809-0.881) (p = 0.007) in the development cohort, and 0.934 (95% CI: 0.909-0.960) vs. 0.877 (95% CI: 0.840-0.914) (p < 0.001) in validation cohort, respectively. Decision curve analysis revealed that the net benefit of the expanded model exceeded that of the base model when the threshold probability was between 0.10 and 0.95 in both the development and external validation cohorts.
Serum antibodies against TP17 and TP47 exhibited promising diagnostic capability for NS and significantly enhanced the predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a non-invasive method for NS diagnosis to substitute invasive lumbar puncture in NS diagnosis.
有创性腰椎穿刺是诊断神经梅毒（NS）的常规方法。我们通过使用荧光素酶免疫吸附试验检测血清苍白密螺旋体特异性针对高度免疫原性抗原 TP0171（TP15）、TP0435（TP17）和 TP0574（TP47）的抗体，研究了一种非侵入性替代方法。
回顾性选择了来自北京和广州队列的 816 名 HIV 阴性疑似 NS 患者，并检测了血清抗 TP15、TP17 和 TP47 IgG 抗体。在北京队列中使用逐步逻辑回归建立了两个诊断预测模型，并在广州队列中进行了外部验证。
血清中针对 TP15、TP17 和 TP47 的抗体在诊断北京队列中的 NS 方面具有中等能力，相应的受试者工作特征曲线（AUC）分别为 0.722（95%置信区间（CI）：0.680-0.762）），0.780（95%CI：0.741-0.817）和 0.774（95%CI：0.734-0.811）。与不包括抗 TP17 和抗 TP47 抗体的基础 NS 诊断模型相比，包含抗 TP17 和抗 TP47 抗体的扩展 NS 预测模型的性能更好，其 AUC 分别为 0.874（95%CI：0.841-0.906）和 0.845（95%CI：0.809-0.881）（p=0.007）在开发队列中，以及分别为 0.934（95%CI：0.909-0.960）和 0.877（95%CI：0.840-0.914）（p<0.001）在验证队列中。决策曲线分析表明，在开发和外部验证队列中，当阈值概率在 0.10 到 0.95 之间时，扩展模型的净收益均超过基础模型。
针对 TP17 和 TP47 的血清抗体对 NS 具有有希望的诊断能力，并显著提高了模型对 NS 诊断的预测准确性。我们的研究强调了血清密螺旋体抗体检测作为一种非侵入性方法替代 NS 诊断中的有创性腰椎穿刺的潜力。
