Center for Clinical Research Dalarna - Uppsala University, Region Dalarna County and Faculty of Medical and Health Sciences, Örebro University, Nissers väg 3, S-791 82, Falun, Sweden.
Clinical Microbiology, Region Jönköping County and Department of Clinical and Experimental Medicine, Linköping University, Sweden.
Ticks Tick Borne Dis. 2020 May;11(3):101390. doi: 10.1016/j.ttbdis.2020.101390. Epub 2020 Jan 27.
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.
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 patients, all LNB patients presented with pleocytosis in CSF. Patients diagnosed as Non-LNB or Other diagnosis were categorized as Controls, all controls presented without pleocytosis in CSF. Multiplex bead array (Luminex) kits were used for analyses of 41 different cytokines/chemokines in CSF (Millipore).
Twenty-eight cytokines/chemokines were detectable in CSF and the levels of 26 of these mediators were significantly higher in LNB patients than in Controls. 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 vs Non-LNB patients, as compared to CXCL13 in CSF. No immune mediator differed significantly, when comparing LNB patients with different clinical presentation on admission or when comparing patients with or without recovery within 2 months of admission.
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 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.
在莱姆神经Borreliosis（LNB）中，免疫反应一直是研究的焦点，但不同细胞因子/趋化因子与 LNB 患者临床表现之间的关系尚未得到充分研究。本研究旨在评估大量细胞因子和趋化因子在脑脊液（CSF）中与诊断、临床表现和接受 LNB 评估的儿童恢复之间的关系。
2010-14 年，在瑞典七家儿科部门招募儿科患者（n=105）。入院时采集血清和 CSF 样本，在开始抗生素治疗前。诊断为明确 LNB 或可能 LNB 的患者被归类为 LNB 患者，所有 LNB 患者均有 CSF 中的白细胞增多。诊断为非 LNB 或其他诊断的患者被归类为对照组，所有对照组均无 CSF 中的白细胞增多。使用多指标 bead 阵列（Luminex）试剂盒（Millipore）分析 CSF 中 41 种不同的细胞因子/趋化因子。
28 种细胞因子/趋化因子可在 CSF 中检测到，26 种这些介质的水平在 LNB 患者中明显高于对照组。在判别分析中，发现四种细胞因子/趋化因子（CXCL1、GM-CSF、IL-7 和 IL-10）的组合能够独立地分离出相关的患者群体。此外，创建了一个 IL-10/CXCL1 比值，并显示在区分 LNB 与非 LNB 患者方面具有更好的诊断性能，优于 CSF 中的 CXCL13。比较入院时临床表现不同的 LNB 患者，或比较入院后 2 个月内有无恢复的患者，没有一种免疫介质的差异有统计学意义。
判别分析显示，区分 LNB 患者与非 LNB 患者的独立最重要的细胞因子/趋化因子（CXCL1、GM-CSF、IL-7 和 IL-10）非常有用。IL-10/CXCL1 比值具有有前途的诊断特征，其性能优于 CSF 中的趋化因子 CXCL13。然而，需要进一步评估这些细胞因子和趋化因子在 LNB 实验室诊断中的未来可能用途，包括具有神经炎症的对照组。在儿科 LNB 患者中，未发现 CSF 免疫介质水平与临床表现或恢复之间存在显著相关性。
