Evaluating the Diagnostic Utility of Serum SEMA7A, SERPINA3, and ITIH4 in Neurosyphilis Using Enzyme-Linked Immunosorbent Assay

Background Neurosyphilis remains challenging to diagnose due to the lack of reliable diagnostic biomarkers. While SEMA7A, SERPINA3, and ITIH4 have shown promise in CSF, their diagnostic utility in serum is unknown. This study evaluated the diagnostic value of these serum biomarkers for identifying neurosyphilis. Methods This cross-sectional study included 72 participants assessed for neurosyphilis at the Department of Dermatology, Southern Medical University Hospital between 2024 and 2026. Participants were classified into neurosyphilis (NS), suspected neurosyphilis (SNS), and non-neurosyphilis (NNS) groups, with further subdivision into symptomatic and asymptomatic subgroups. Serum biomarker levels were measured using ELISA. Results Serum ITIH4 levels differed significantly among the neurosyphilis (NS), suspected neurosyphilis (SNS), and non-neurosyphilis (NNS) groups (P = 0.0357), showing a decreasing trend from NNS to SNS to NS. Although symptomatic NS patients had higher serum ITIH4 levels than asymptomatic NS patients, the difference did not reach statistical significance. ROC analysis demonstrated modest diagnostic performance of ITIH4 for distinguishing NS from NNS (AUC = 0.6771). In contrast, SERPINA3 showed poor discriminatory ability (AUC = 0.5668), whereas SEMA7A showed no diagnostic value (AUC = 0.5000), with no significant differences observed across diagnostic groups or symptomatic subgroups. Conclusion Among the evaluated serum biomarkers, ITIH4 demonstrated the greatest potential for neurosyphilis assessment, showing a significant overall group difference and modest discriminatory ability between NS and NNS patients. Clinical trial registration Not applicable. This was a cross-sectional observational study and was not a clinical trial.