Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

Wurong Li,Junhua Gao,Haoxiao Chang,Meijuan Jiang,Yuming Huang,Wenqing Wu,Dongmei Xu,Linlin Yin,Xinghu Zhang,Yun Xu

doi:10.3389/fneur.2020.00062

Abstract

Objective: To explore cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and neurofilament light proteins (NFL) in patients with neurosyphilis (NS).Methods: We enrolled 71 NS patients (41 early-NS and 30 late-NS patients) and 20 syphilis but non-NS patients whose CSF samples were collected. The CSF levels of the microglial activation biomarker sTREM2 and neuronal injury biomarker NFL were measured using ELISA.Results: CSF sTREM2 levels were significantly higher in NS patients compared to those in syphilis/non-NS patients (p < 0.001). In a subgroup analysis, the CSF sTREM2 levels elevated significantly in late-NS patients than those in early-NS patients (p < 0.001). The CSF sTREM2 levels in early-NS group were also significantly higher than those in syphilis/non-NS group (p = 0.024). Like CSF sTREM2, similar differences between groups were also found in CSF NFL. There was a moderate correlation between CSF sTREM2 and CSF NFL (r = 0.406, p < 0.001) in NS group.Conclusions: CSF sTREM2 levels elevated in NS and peaked at the late stage, suggesting that CSF sTREM2 may be a useful marker to quantify microglia activation in NS and may play a role in the progression of NS. The positive correlation between CSF sTREM2 and CSF NFL indicates a linkage between microglial activation and neuronal injury in NS.

Highlights

NS is a chronic infectious disease caused by Treponema pallidum invading the central nervous system (CNS), which mainly damages the meninges, blood vessels, and brain, and spinal cord parenchyma [1, 2]
There was a moderate correlation between CSF soluble TREM2 (sTREM2) values and CSF Neurofilament light proteins (NFL) (r = 0.406, p < 0.001; Figure 2A) in NS group, while no significant correlation was found between CSF sTREM2 and CSF NFL in the syphilis/non-NS group (r = 0.02, p = 0.95; Figure 2B)
We investigated the changes of CSF sTREM2 levels at different stages of NS and explored the relationship between this microglial activation marker and neuronal injury marker NFL

Summary

Introduction

NS is a chronic infectious disease caused by Treponema pallidum invading the central nervous system (CNS), which mainly damages the meninges, blood vessels, and brain, and spinal cord parenchyma [1, 2]. Increased soluble TREM2 (sTREM2) levels in CSF have been found in HIV infection [8], multiple sclerosis (MS) [9, 10], and Alzheimer’s disease (AD) [11, 12]. Over activation of microglia may result in neuronal loss and neuropil damage [3, 4]. The levels of CSF NFL can reflect the degree of neuronal injury of the CNS and severity of the disease to a certain extent. A correlation between microglial activation and neuronal injury was found in HIV infection [8]. NS patients, especially in the late stage, have mental abnormalities, cognitive changes, and brain atrophy [1, 2], indicating that NS patients have a degree of neuronal loss and injury.

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Discussion

Conclusion