Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：腰椎穿刺（LP）是诊断神经梅毒（NS）的常规方法。我们研究了一种非侵入性的替代方法来检测针对高免疫原性抗原TP0171（TP15）的血清梅毒螺旋体特异性抗体，TP0435(TP17),和TP0574（TP47）通过使用荧光素酶免疫吸附测定（LISA）。
方法：回顾性选择来自北京和广州队列的816例HIV阴性疑似NS患者，并检测血清抗TP15、TP17和TP47IgG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外部验证。
结果：在北京队列中，针对TP15，TP17和TP47的血清抗体显示出中度NS诊断能力，相应的AUC为0.722（95％CI：0.680-0.762），0.780（95%CI：0.741-0.817），和0.774（95%CI：0.734-0.811），分别。与抗TP17和抗TP47抗体集成的扩展NS预测模型在开发队列中显示出比没有抗TP17和抗TP47抗体的基础NS诊断模型更好的性能，AUC为0.874（95％CI：0.841-0.906）vs0.845（95％CI：0.809-0.881）（p=0.007），和0.934（95％CI：0.909-0.960）与0.877（95％CI：0.840-0.914）（p<0.001），分别。决策曲线分析（DCA）显示，在开发和外部验证队列中，当阈值概率在0.10和0.95之间时，扩展模型的净收益超过了基础模型的净收益。
结论：抗TP17和TP47的血清抗体对NS具有良好的诊断能力，并显着提高了NS诊断模型的预测准确性。我们的研究强调了血清密螺旋体抗体检测作为NS诊断的非侵入性方法代替NS诊断中的侵入性LP的潜力。
方法：回顾性选择来自北京和广州队列的816例HIV阴性疑似NS患者，并检测血清抗TP15、TP17和TP47IgG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外部验证。
结果：在北京队列中，针对TP15，TP17和TP47的血清抗体显示出中度NS诊断能力，相应的AUC为0.722（95％CI：0.680-0.762），0.780（95%CI：0.741-0.817），和0.774（95%CI：0.734-0.811），分别。与抗TP17和抗TP47抗体集成的扩展NS预测模型在开发队列中显示出比没有抗TP17和抗TP47抗体的基础NS诊断模型更好的性能，AUC为0.874（95％CI：0.841-0.906）vs0.845（95％CI：0.809-0.881）（p=0.007），和0.934（95％CI：0.909-0.960）与0.877（95％CI：0.840-0.914）（p<0.001），分别。决策曲线分析（DCA）显示，在开发和外部验证队列中，当阈值概率在0.10和0.95之间时，扩展模型的净收益超过了基础模型的净收益。
结论：抗TP17和TP47的血清抗体对NS具有良好的诊断能力，并显着提高了NS诊断模型的预测准确性。我们的研究强调了血清密螺旋体抗体检测作为NS诊断的非侵入性方法代替NS诊断中的侵入性LP的潜力。
