BACKGROUND Lyme neuroborreliosis (LNB) is characterized by cerebrospinal fluid (CSF) inflammation with several cytokines/chemokines and B-lymphocytes. Clinically, LNB in children may be difficult to discriminate from non-Lyme aseptic meningitis (NLAM). We aimed to identify CSF cytokine/chemokine patterns in children with LNB, NLAM and controls and elucidate the diagnostic value of these cytokines/chemokines alone or in combination to discriminate between LNB and NLAM. METHODS Children with symptoms suggestive of LNB were included prospectively and categorized as LNB, NLAM or controls (no pleocytosis). Cytokines/chemokines in CSF were measured by multiplex bead assays and levels were compared between the three groups by nonparametric statistical tests. Previous results from the same children on the established biomarker, CXCL13, were included in the statistical analyses. The diagnostic properties of cytokines/chemokines to discriminate between LNB and NLAM were determined by receiver operating characteristic curve analyses with estimates of area under curve (AUC). To explore diagnostic properties of combinations of cytokines/chemokines, prediction models based on logistic regression were used. RESULTS We included 195 children with LNB (n = 77), NLAM (n = 12) and controls (n = 106). Children with LNB had higher CSF levels of CCL19, CCL22 and CXCL13 compared to NLAM and controls, whereas INFγ was higher in NLAM than in LNB and controls. CXCL13 was the superior single cytokine/chemokine to discriminate LNB from NLAM (AUC 0.978). The combination CXCL13/CCL19 (AUC 0.992) may possibly improve the specificity for LNB, especially for children with moderate CXCL13 levels. CONCLUSIONS The intrathecal immune reaction in LNB is characterized by B cell associated chemokines. Whether the combination CXCL13/CCL19 further improves discrimination between LNB and NLAM beyond the diagnostic improvements by CXCL13 alone needs to be tested in new studies.

中文翻译：

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莱姆神经疏螺旋体病患儿的脑脊液细胞因子和趋化因子；模式和诊断实用程序

背景莱姆神经疏螺旋体病(LNB) 的特征是脑脊液(CSF) 炎症与多种细胞因子/趋化因子和B 淋巴细胞。临床上，儿童的 LNB 可能难以与非莱姆病无菌性脑膜炎 (NLAM) 区分开来。我们旨在确定 LNB、NLAM 和对照儿童的 CSF 细胞因子/趋化因子模式，并阐明这些细胞因子/趋化因子单独或组合的诊断价值，以区分 LNB 和 NLAM。方法 前瞻性纳入具有提示 LNB 症状的儿童，并将其归类为 LNB、NLAM 或对照（无细胞增多症）。CSF 中的细胞因子/趋化因子通过多重珠试验测量，并通过非参数统计检验比较三组之间的水平。先前来自相同儿童的既定生物标志物 CXCL13 的结果，被纳入统计分析。细胞因子/趋化因子区分 LNB 和 NLAM 的诊断特性通过受试者操作特征曲线分析和曲线下面积 (AUC) 估计值来确定。为了探索细胞因子/趋化因子组合的诊断特性，使用了基于逻辑回归的预测模型。结果 我们纳入了 195 名患有 LNB（n = 77）、NLAM（n = 12）和对照组（n = 106）的儿童。与 NLAM 和对照组相比，LNB 儿童的 CCL19、CCL22 和 CXCL13 CSF 水平较高，而 NLAM 中的 INFγ 高于 LNB 和对照组。CXCL13 是区分 LNB 和 NLAM 的最佳单一细胞因子/趋化因子（AUC 0.978）。CXCL13/CCL19 组合 (AUC 0.992) 可能会提高 LNB 的特异性，尤其是对于 CXCL13 水平中等的儿童。结论 LNB鞘内免疫反应以B细胞相关趋化因子为特征。CXCL13/CCL19 组合是否能进一步改善 LNB 和 NLAM 之间的区分，超出单独 CXCL13 的诊断改善，需要在新的研究中进行测试。