Epigenetic Changes in Cerebrospinal Fluid and Blood of People With Neurosyphilis

Epigenetic changes within immune cells may contribute to neuroinflammation during bacterial infection, but their role in neurosyphilis (NS) pathogenesis and response has not yet been established. We longitudinally analyzed DNA methylation and RNA expression in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) from 11 participants with laboratory-confirmed NS (CSF Venereal Disease Research Laboratory test positive) and 11 matched controls with syphilis without NS (non-NS). DNA methylation profiles from CSF and PBMCs of participants with NS significantly differed from those of participants with non-NS. Some genes associated with these differentially methylated sites had corresponding RNA expression changes in the CSF (111/1097 [10.1%]), and included genes involved in B cell activation and insulin-response pathways. Despite antibiotic treatment, approximately 80% of CSF methylation changes associated with NS persisted, suggesting that epigenetic scars accompanying NS may persistently affect immunity following infection. Future studies must examine whether these sequelae are clinically meaningful.