Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis

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.

CSF sTREM2 in neurological diseases: a two-sample Mendelian randomization study

“…Triggering receptor expressed on myeloid cells 2 (TREM2), which is mainly expressed by microglia, the resident immunocytes in central nervous system (CNS), have been extensively studied and found associated with microglia functions [ 1 ]. Evidence from observational studies indicates that the levels of soluble TREM2 (the secreted ectodomain of TREM2, sTREM2) were higher in cerebrospinal fluid (CSF) of patients with CNS disorders of different causes, including inflammatory [ 2 – 4 ], neurodegenerative [ 5 – 11 ], and vascular diseases [ 12 , 13 ]. However, given careful study design of observational analyses, whether CSF sTREM2 levels account for the observed development of these neurological disorders remains unclear.…”

High levels of cerebrospinal fluid soluble triggering receptor expressed on myeloid cells 2 might be a biomarker of activity in pediatric patients with MOG-AD

“…By comparing the effects of natalizumab and mitoxantrone, only CSF sTRME2 has shown the potential utility as a biomarker for MS treatment effects ( 12 ). In addition, the level of CSF sTREM2 was increased in patients with neurosyphilis (NS), and peaked at the late stage, compared with the control groups ( 23 ).…”

Diagnostic tools for neurosyphilis: a systematic review

“…Because current tests lack sensitivity, new research has been exploring novel CSF biomarkers and their potential to aid in the diagnosis or exclusion of NS. For instance, myeloid and microglial activation markers such as MIF (Macrophage migration inhibitory factor) and sTREM2 (soluble Triggering receptor expressed on myeloid cells 2) have been reported to be differentially expressed in the CSF of patients with NS and have emerged as promising tools for establishing a diagnosis, particularly in the setting where non-treponemal tests are negative but there is high clinical suspicion [ 36 , 37 ]. Furthermore, Zhang et al reported that several CSF proteins such as neurogranin, BACE1, and Tau are increased in patients with Alzheimer’s Disease in comparison to those with NS, which may be useful in the setting of patients with cognitive decline and a past history of syphilis [ 38 ].…”