Background The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. Methods We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 non-neurosyphilis and 10 neurosyphilis patients. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 non-neurosyphilis, 51 untreated neurosyphilis, and 31 post-treatment neurosyphilis patients were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman's analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. Results A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis were positive correlations with WBC counts, RPR titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an AUC of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. Conclusions CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.

中文翻译：

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中性粒细胞相关蛋白作为神经梅毒患者脑脊液中升高的新型生物标志物

背景 神经梅毒的免疫病理学机制尚未完全阐明，神经梅毒的诊断面临挑战。方法 我们使用抗体微阵列检测从 6 名非神经梅毒患者和 10 名神经梅毒患者收集的脑脊液 (CSF) 样本中的 640 种蛋白质。使用酶联免疫吸附测定对 46 名非神经梅毒患者、51 名未经治疗的神经梅毒患者和 31 名治疗后神经梅毒患者的 CSF CXCL1、CXCL8、G-CSF、LCN2、MMP8 和 MMP9 水平进行定量。使用斯皮尔曼分析评估这些蛋白质水平与神经梅毒临床参数之间的关联，并使用受试者工作特征曲线评估这些蛋白质在神经梅毒中的诊断性能。结果共鉴定出102个神经梅毒与非神经梅毒之间的差异表达蛋白。神经梅毒中中性粒细胞相关蛋白（CXCL1、CXCL8、G-CSF、LCN2、MMP8和MMP9）水平显着升高，与脑脊液中WBC计数、RPR滴度和蛋白浓度呈正相关。CSF CXCL8、MMP9 和 LCN2 组合诊断神经梅毒的 AUC 为 0.92，超过了 CSF RPR。结论 CXCL1、CXCL8、G-CSF、LCN2、MMP8、MMP9可能与神经梅毒中枢神经系统损害有关。CSF CXCL8、MMP9 和 LCN2 的组合是诊断神经梅毒的有前途的生物标志物。