These findings demonstrate that the IgM immunoblot provides a distinct serological signature, offering a valuable non-invasive aid for discriminating NS from LS.<h4>Importance</h4>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. This evidence concerns the gene CD40LG and latent syphilis.