W183 - DNA Methylation and RNA Expression on Immune Cells in the Cerebrospinal Fluid of Patients with Neurosyphilis

Michael Corley – Weill Cornell Medicine; Shelli Farhadian – Yale School of Medicine; Christina Marra – University of Washington; Sameet Mehta – Yale School of Medicine; Jennifer Yoon – Yale School of Medicine

Abstract Text: Neurosyphilis (NS) is a complication of syphilis that manifests with a range of neurological conditions, including stroke and neuropsychiatric disease. Although the prevalence of both syphilis and neurosyphilis is rising, the pathogenesis of NS and its sequelae after treatment are not well understood. We longitudinally analyzed DNA methylation and RNA expression profiles from cerebrospinal fluid (CSF) cells from diagnosis to one year post-treatment from 12 adults with laboratory confirmed NS (CSF venereal disease research laboratory reactive and >5 cells/uL) and 11 controls who had syphilis without neurosyphilis (non-NS), matched for age, sex, HIV status, and serum rapid plasma reagin titer. We utilized the Illumina MethylationEPIC platform to assay DNA methylation at single nucleotide resolution from ~850K CpG sites. DNA methylation profiles from the CSF of participants with NS were significantly different from those of participants with non-NS. Among the pre-treatment CSF samples, status of NS vs non-NS was the primary driver of methylation differences among the samples, with 1660 differentially methylated CpG sites (false discovery rate < 0.01 and Effect size > 10%), which were enriched in genomic regions regulated by the GATA3 transcription factor. More than 80% of these DNA methylation changes persisted after treatment. Cell population imputation found B cell elevation within the CSF of patients with neurosyphilis, which resolved post-treatment. This pattern corresponded to concomitant RNA expression changes among B-cell genes in the same samples. Despite treatment for NS, these results suggest persistent CNS immune dysregulation. Future studies must examine whether these sequelae are clinically meaningful.