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脑脊液 CXCL13 作为儿童神经莱姆病的诊断标志物:一项回顾性病例对照研究。

Cerebrospinal fluid CXCL13 as a diagnostic marker of neuroborreliosis in children: a retrospective case-control study.

机构信息

Institute of Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3001, Bern, Switzerland.

Department of Pediatrics, Bern University Hospital, University of Bern, Bern, Switzerland.

出版信息

J Neuroinflammation. 2017 Aug 31;14(1):173. doi: 10.1186/s12974-017-0948-9.

Abstract

BACKGROUND

Lyme neuroborreliosis (LNB) is a frequent manifestation of Lyme disease in children and its current diagnosis has limitations. The elevation of the chemokine CXCL13 in the cerebrospinal fluid (CSF) of adult patients with LNB has been demonstrated and suggested as a new diagnostic marker. Our aim was to evaluate this marker in the CSF of children with suspected LNB and to determine a CXCL13 cut-off concentration that would discriminate between LNB and other central nervous system (CNS) infections.

METHODS

For this single-center retrospective case-control study we used a diagnostic-approved ELISA to measure CXCL13 concentrations in the CSF of 185 children with LNB suspicion at presentation. Patients were classified into definite LNB (cases), non-LNB (controls with other CNS affections), and possible LNB. A receiver-operating characteristic curve was generated by comparison of cases and controls.

RESULTS

CXCL13 was significantly elevated in the CSF of 53 children with definite LNB (median 774.7 pg/ml) compared to 91 control patients (median 4.5 pg/ml, p < 0.001). A cut-off of 55 pg/ml resulted in a sensitivity of 96.7% and a specificity of 98.1% for the diagnosis of definite LNB and the test exhibited a diagnostic odds ratio of 1525.3. Elevated CSF CXCL13 levels were also detected in three controls with viral meningitis (enterovirus n = 1, varicella-zoster virus n = 2) while other CNS affections such as idiopathic facial palsy did not lead to CXCL13 elevation. Of the 41 patients with possible LNB, 27% had CXCL13 values above the cut-off of 55 pg/ml (median 16.7 pg/ml).

CONCLUSIONS

CSF CXCL13 is highly elevated in children during early LNB as previously shown in adults. CXCL13 is a highly sensitive and specific marker that helps to differentiate LNB from other CNS affections in children.

摘要

背景

莱姆神经Borreliosis(LNB)是儿童莱姆病的常见表现,其目前的诊断存在局限性。已经证明,成人 LNB 患者脑脊液(CSF)中的趋化因子 CXCL13 升高,并被提议作为新的诊断标志物。我们的目的是评估疑似 LNB 儿童的这种标志物,并确定区分 LNB 和其他中枢神经系统(CNS)感染的 CXCL13 截止浓度。

方法

在这项单中心回顾性病例对照研究中,我们使用诊断批准的 ELISA 测量了 185 名有 LNB 疑似症状的儿童的 CSF 中 CXCL13 的浓度。患者被分为明确的 LNB(病例)、非 LNB(其他 CNS 感染的对照组)和可能的 LNB。通过比较病例和对照组生成了受试者工作特征曲线。

结果

与 91 名对照组患者(中位数 4.5 pg/ml,p < 0.001)相比,53 名明确 LNB 患儿的 CSF 中 CXCL13 显著升高(中位数 774.7 pg/ml)。55 pg/ml 的截值对明确 LNB 的诊断具有 96.7%的敏感性和 98.1%的特异性,并且该试验具有 1525.3 的诊断优势比。3 名病毒性脑膜炎患儿的 CSF 中也检测到升高的 CXCL13 水平(肠道病毒 n = 1,水痘带状疱疹病毒 n = 2),而其他 CNS 病变如特发性面瘫则不会导致 CXCL13 升高。在 41 名可能的 LNB 患者中,27%的患者 CXCL13 值高于 55 pg/ml 的截值(中位数 16.7 pg/ml)。

结论

如前所述,在成人 LNB 中,儿童早期 LNB 期间 CSF CXCL13 高度升高。CXCL13 是一种高度敏感和特异的标志物,有助于区分儿童 LNB 和其他 CNS 病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4174/5580331/77485ec4e636/12974_2017_948_Fig1_HTML.jpg

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