Evaluation of cerebrospinal fluid ubiquitin C-terminal hydrolase-L1, glial fibrillary acidic protein, and neurofilament light protein as novel markers for the diagnosis of neurosyphilis among HIV-negative patients

Objectives: To evaluate the possibility of using cerebrospinal fluid (CSF) ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light protein (NF-L) for the diagnosis of neurosyphilis (NS).Methods: A cross-sectional study of 576 subjects was conducted at Zhongshan Hospital from January 2021 to August 2022 to evaluate the diagnostic accuracy of CSF UCH-L1, GFAP, and NF-L for NS and ana-lyze their correlations with CSF rapid plasma reagin (RPR), white blood cells (WBCs), and protein.Results: Patients with NS had higher CSF UCH-L1, GFAP, and NF-L levels than patients with syphilis/non-NS and nonsyphilis. Using a cut-off point of 652.25 pg/ml, 548.89 pg/ml, and 48.38 pg/ml, CSF UCH -L1, GFAP, and NF-L had a sensitivity of 85.11%, 76.60%, and 82.98%, with a specificity of 92.22%, 85.56%, and 91.11%, respectively, for NS diagnosis. Moreover, parallel and serial testing algorithms improved their sensitivity and specificity to 93.62% and 98.89%, respectively. Interestingly, levels between patients with NS who are CSF RPR-positive and-negative did not differ and showed a weak or moderate correlation with WBC and CSF protein in patients with syphilis.Conclusion: CSF UCH-L1, GFAP, and NF-L can be used as novel markers for the diagnosis of NS, indepen-dent of CSF RPR, WBC, and proteins.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

CSF UCH-L1, GFAP, and NF-L can serve as novel markers for the diagnosis of neurosyphilis. They exhibit high sensitivity and specificity for NS diagnosis with specific cut-off points. Furthermore, they show weak or moderate correlations with CSF RPR, WBC, and protein, and can be used independently of these markers.