A distinct IgM immunoblot signature differentiates neurosyphilis from latent syphilis.

UNLABELLED: Accurately differentiating neurosyphilis (NS) from latent syphilis (LS) is essential, as it directly guides therapeutic decisions and prevents devastating neurological complications. However, this differentiation remains a significant clinical challenge because it currently relies on cerebrospinal fluid analysis-an invasive and resource-intensive procedure that is not suitable for all patients. To address this, we evaluated whether a detailed Treponema pallidum-specific immunoglobulin M (IgM) immunoblot profile could offer a robust non-invasive diagnostic tool. We conducted a comprehensive analysis of serum samples from 319 patients (74 NS and 245 LS), assessing the IgM positive rate, antigen-specific reactivity (TP15, TP17, TP45, and TP47), and antibody reaction intensity (gray value). Our analysis revealed that NS patients exhibited a significantly stronger and broader IgM response, evidenced by a higher overall positive rate (45.9% vs 26.1%, P = 0.001) and elevated reactivity to TP17, TP45, and TP47 antigens. The antibody reaction intensity for these antigens was also significantly stronger in the NS group. Critically, multivariable analysis identified a higher serum the Toluidine Red Unheated Serum Test titer (odds Ratio [OR] = 1.025 per unit, 95% confidence interval [CI]: 1.009-1.041, P = 0.003) and a greater number of positive antigens (OR = 1.663, 95% CI: 1.100-2.512, P = 0.016) as independent risk factors for NS, while male sex was an independent protective factor (OR = 0.325, 95% CI: 0.179-0.591, P < 0.001). These findings demonstrate that the IgM immunoblot provides a distinct serological signature, offering a valuable non-invasive aid for discriminating NS from LS.

IMPORTANCE: This study addresses a fundamental challenge in syphilis management: determining which patients with latent syphilis are at high risk for neurosyphilis without relying on invasive lumbar puncture. By analyzing a simple blood test that profiles the immunoglobulin M antibody response in detail, we discovered that patients with neurosyphilis have a distinctly stronger and broader immune reaction. We further identified key risk factors, including higher antibody levels and reactivity to multiple targets. These findings are significant because they provide doctors with a practical, non-invasive tool to stratify patient risk more accurately. This can help optimize clinical decision-making, ensuring that lumbar punctures are performed on patients who need them most while avoiding unnecessary procedures for others, ultimately leading to better and more personalized patient care.