Refining a non-invasive prediction model for neurosyphilis diagnosis by using immunoassay to detect serum anti-TP0435 (TP17) and TP0574 (TP47) IgG antibodies: two-centre cross-sectional retrospective study in China
Authors: Wujian Ke, Cailing Ao, Liuyuan Wang, Xiaohui Zhang, Jingwei Shui, Jianhui Zhao, Liping Huang, Xinying Leng, Rui Zhu, Haiying Wang, Wenjia Weng, Lianhong Zheng, None Ligang Yang, Shixing Tang
Journal: Clinical Microbiology and Infection (2024)

ObjectivesInvasive lumbar puncture (LP) is the conventional method for diagnosing neurosyphilis (NS). We investigated a noninvasive 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 (LISA).Methods816 HIV-negative patients suspected of NS from Beijing and Guangzhou cohort were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibody. Two diagnostic prediction models were developed using stepwise logistic regression in Beijing cohort, and evaluated in Guangzhou cohort for external validation.ResultsSerum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in Beijing cohort and the corresponding AUCs were 0.722 (95% 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 (DCA) 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.ConclusionsSerum antibodies against TP17 and TP47 exhibited promising diagnostic capability for NS and significantly enhanced predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a noninvasive method for NS diagnosis to substitute invasive LP in NS diagnosis. Invasive lumbar puncture (LP) is the conventional method for diagnosing neurosyphilis (NS). We investigated a noninvasive 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 (LISA). 816 HIV-negative patients suspected of NS from Beijing and Guangzhou cohort were retrospectively selected and tested for serum anti-TP15, TP17, and TP47 IgG antibody. Two diagnostic prediction models were developed using stepwise logistic regression in Beijing cohort, and evaluated in Guangzhou cohort for external validation. Serum antibodies against TP15, TP17, and TP47 showed moderate capability for NS diagnosis in Beijing cohort and the corresponding AUCs were 0.722 (95% 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 (DCA) 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 predictive accuracy of model for NS diagnosis. Our study highlights the potential of serum treponemal antibody detection as a noninvasive method for NS diagnosis to substitute invasive LP in NS diagnosis.