Cytokines in cerebrospinal fluid and serum as biomarkers are associated with the diagnosis and efficacy evaluation of neurosyphilis

Abstract Background Neurosyphilis remains a chronic infectious disease within central nervous system infected by Treponema pallidum (TP). At present, the diagnosis and efficacy evaluation of neurosyphilis still facing clinical challenges. It has been reported that cytokines, which play multiple roles in neuroinflammation, showed abnormal expression patterns in neurosyphilis. To search for potential biomarkers of neurosyphilis, we analyzed the changes of cytokine profiles in cerebrospinal fluid (CSF) and serum of neurosyphilis. This may provide insight into clinical values for neurosyphilis. Methods Using the quantitative antibody array platform, we measured 80 cytokines expression in the CSF and serum of 16 subjects. 9 patients diagnosed with neurosyphilis, included samples before and after antibiotic treatment. 7 patients with non-inflammatory neurological diseases (NIND) were used as controls. Compared to the differences in cytokine expression between groups and analyzed to the correlations between cytokines and clinical CSF parameters. The ability of valuable biomarkers to diagnosis of neurosyphilis was evaluated by receiver operating characteristic (ROC) curves. Results We observed significantly increased of multiple cytokines (26/80) in CSF of neurosyphilis were significantly increased compared to the NIND group. Concentrations of 15 cytokines were significantly decreased after treatment, of which 11 cytokines were down regulated to the levels were similar to the NIND group. Most CSF cytokine concentrations consistently correlated with clinical parameters, positively related to white blood cells (WBCs, 42/80), total protein (36/80), and albumin quotient (Qalb, 37/80) and negatively related to Glucose level (22/80). More than 40 cytokines concentrations correlated with each other in CSF, most of them were positively correlated. But correlations between CSF cytokine and serum cytokine values were scarce (6/80). The area under the ROC curve (AUC) of G-CSF, ICAM-1, CCL4, CCL19 and IL-12p40 in CSF were all greater than 0.9, with high diagnostic values. Conclusions Our data showed that multiple CSF cytokines were highly expressed of neurosyphilis, and their levels were significantly reduced after antibiotic treatment. Meanwhile, these cytokines were significantly correlated with various CSF parameters. The AUCs of G-CSF, ICAM-1, CCL4, CCL19 and IL-12p40 were all greater than 0.9, suggesting that these cytokines may serve as potential biomarkers for neurosyphilis. Unfortunately, more meaningful results were not observed in the analysis at the serum level. Therefore, along with previous related reports, it is believed that CSF measures are irreplaceable in the current clinical diagnosis, and the combined dynamic detection of multiple cytokines such as G-CSF, ICAM-1, CCL4, CCL19 and IL-12p40 in CSF can serve as a supplementary diagnostic tool for neurosyphilis.