A distinct IgM immunoblot signature differentiates neurosyphilis from latent syphilis.

< 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.