In Lyme neuroborrelios (LNB), the immune response has been in focus, but the association between different cytokines/chemokines and clinical manifestations in LNB patients has not been fully investigated. The aim of this study was to evaluate a large number of cytokines and chemokines in cerebrospinal fluid (CSF) in relation to diagnosis, clinical presentation and recovery in children being evaluated for LNB.

Materials and methods

Pediatric patients (n = 105) were recruited at seven Swedish pediatric departments during 2010–14. Serum and CSF samples were drawn on admission, before start of antibiotic treatment. Patients diagnosed as Definite LNB or Possible LNB were categorized as LNB_tot patients, all LNB_tot patients presented with pleocytosis in CSF. Patients diagnosed as Non-LNB or Other diagnosis were categorized as Controls_tot, all controls_tot presented without pleocytosis in CSF.

Multiplex bead array (Luminex) kits were used for analyses of 41 different cytokines/chemokines in CSF (Millipore).

Results

Twenty-eight cytokines/chemokines were detectable in CSF and the levels of 26 of these mediators were significantly higher in LNB_tot patients than in Controls_tot. In a discriminant analysis, a combination of four cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) were shown to independently separate relevant patient groups. Furthermore, an IL-10/CXCL1 ratio was created and shown to have an improved diagnostic performance in distinguishing LNB_tot vs Non-LNB patients, as compared to CXCL13 in CSF. No immune mediator differed significantly, when comparing LNB_tot patients with different clinical presentation on admission or when comparing patients with or without recovery within 2 months of admission.

Conclusion

A discriminant analysis was shown to be useful to distinguish the independently most important cytokines/chemokines (CXCL1, GM-CSF, IL-7 and IL-10) in CSF, in order to discriminate LNB_tot patients from Non-LNB patients. An IL-10/CXCL1 ratio was shown to have a promising diagnostic profile with a better performance than the chemokine CXCL13 in CSF. However, further evaluation is required to address future possible usefulness of these cytokines and chemokines in laboratory diagnostics in LNB, including control groups with neuro-inflammation. No significant associations were found between CSF immune mediator levels and clinical presentation or recovery in pediatric LNB patients.

中文翻译：

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脑脊髓液中的细胞因子和趋化因子与莱姆病神经性硼中毒的儿童诊断，临床表现和恢复有关。

在莱姆氏神经硼蛋白（LNB）中，免疫反应一直是关注的焦点，但是LNB患者中不同细胞因子/趋化因子与临床表现之间的关联尚未得到充分研究。这项研究的目的是评估与评估LNB的儿童的诊断，临床表现和恢复有关的脑脊髓液（CSF）中的大量细胞因子和趋化因子。

材料和方法

2010-14年间，瑞典的七个儿科部门招募了儿科患者（n = 105）。在开始抗生素治疗之前，在入院时抽取血清和脑脊液样品。诊断为定LNB或可能LNB患者被归类为LNB _TOT患者，所有LNB _TOT带有脑脊液细胞增多的患者。诊断为非LNB或其他诊断患者被归类为控制_地合计，所有控件_TOT没有脑脊液细胞增多呈现。

多重磁珠阵列（Luminex）试剂盒用于分析CSF（Millipore）中的41种不同的细胞因子/趋化因子。

结果

二十八个细胞因子/趋化因子在脑脊液检测和这些介质的26水平LNB均显著高于_托特患者比对照_TOT。在判别分析中，显示四种细胞因子/趋化因子（CXCL1，GM-CSF，IL-7和IL-10）的组合可独立分离相关患者组。此外，与CSF中的CXCL13相比，创建了IL-10 / CXCL1比并显示出在区分LNB _tot和非LNB患者方面具有更好的诊断性能。当比较入院时具有不同临床表现的LNB _tot患者或比较入院2个月内有或没有恢复的患者时，免疫介质没有显着差异。

结论

判别分析显示可用于区分CSF中独立的最重要的细胞因子/趋化因子（CXCL1，GM-CSF，IL-7和IL-10），以区分LNB _tot患者与非LNB患者。结果表明，IL-10 / CXCL1比具有比CSF中趋化因子CXCL13更好的诊断性能。但是，需要进一步评估以解决这些细胞因子和趋化因子在LNB实验室诊断中未来可能的有用性，包括神经炎症对照组。小儿LNB患者的脑脊液免疫介质水平与临床表现或恢复之间无显着关联。