2348. Distinct cerebrospinal fluid immune proteins mark neurosyphilis

Background Neurosyphilis (NS) is increasing in prevalence in the U.S. but remains challenging to diagnose, particularly in asymptomatic cases. Uncovering central nervous system (CNS) specific immune pathways may shed light on disease pathogenesis and potential biomarkers. Methods Paired cerebrospinal fluid and blood were collected from participants with syphilis without neurological symptoms from 2013–2019. Participants were categorized as NS if CSF VDRL was positive and matched by RPR and date of enrollment to participants without neurosyphilis (non-NS), defined by VDRL negative and CSF WBC < 5/uL. Paired CSF and plasma were run on a 71-plex chemokine/cytokine array, high-sensitivity (SIMOA) ELISA for markers of neuronal and astrocyte injury, and ELISA for neopterin, a marker of intrathecal macrophage/microglial activation. Comparisons between NS and non-NS were made using T-tests and Wilcoxon rank-sum tests, with p-values adjusted (FDR) for multiple comparisons. Results 24 participants were enrolled with characteristics as in Table 1. HIV status, age, race/ethnicity, and plasma RPR values did not significantly differ by group. Six cytokines were significantly (p< 0.05, FDR < 0.10) different in the CSF in NS compared to non-NS, including MIG/CXCL9, IP-10/CXCL10, macrophage-derive-chemokine (MDC), IL-8/CXCL8 and BCA-1/CXCL13, which was previously recognized as elevated in NS (Figure 1B). Neopterin, but no neuronal or astrocyte markers, was elevated in the CSF of NS versus non-NS (p < 0.001) (Figure 1A). After adjusting for multiple comparisons, there were no significant differences between markers in plasma of NS vs non-NS. Differences between NS and non-NS groups were not affected by HIV status. Conclusion There is a distinct and compartmentalized CNS immune response occurring in individuals with NS, as indicated by elevated markers of CNS inflammation and of key chemoattractants, the CXC family of proteins. Elevation of neopterin, but not neuronal injury markers suggest asymptomatic disease elicits an immune response without incurring neuronal damage. These immune biomarkers can provide insight into neuroinflammatory processes during asymptomatic NS and should be explored as potential CSF biomarkers of NS. Disclosures Magnus Gisslen, MD, PhD, Amgen: Honoraria|AstraZeneca: Advisor/Consultant|AstraZeneca: DSMB membership|Biogen: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|GlaxoSmithKline/ViiV: Advisor/Consultant|GlaxoSmithKline/ViiV: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Novo Nordic: Honoraria|Novocure: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Honoraria.