Hytönen Jukka, Kortela Elisa, Waris Matti, Puustinen Juha, Salo Jemiina, Oksi Jarmo
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
J Neuroinflammation. 2014 Jun 11;11:103. doi: 10.1186/1742-2094-11-103.
Laboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi-specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases.
CXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples.
The CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment.CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations decreased statistically significantly with the treatment.
These results clearly indicate that highly elevated CSF CXCL13 levels are strongly associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an excellent biomarker in differentiating LNB from viral CNS infections and from other neuroinflammatory conditions.
莱姆病神经伯氏疏螺旋体病（LNB）的实验室诊断部分基于鞘内伯氏疏螺旋体特异性抗体产生的检测（抗体指数（AI）升高）。然而，早期LNB患者的AI可能为阴性，相反，抗生素治疗后AI可能会持续升高数月。最近的研究表明，脑脊液（CSF）中的趋化因子CXCL13是活动性LNB的生物标志物。此外，脑脊液新蝶呤水平测定已被用于评估多种疾病中的神经炎症程度。
对366例经回顾性鉴定的个体的脑脊液样本中的CXCL13浓度进行了分析。这些样本代表治疗前的LNB患者（38例）、非LNB对照患者、蜱传脑炎、中枢神经系统（CNS）水痘带状疱疹病毒感染、CNS单纯疱疹病毒感染、CNS HHV6感染、CNS肠道病毒感染以及未经治疗的神经梅毒。该样本组还包括来自多发性硬化症和其他神经炎症性疾病患者的样本。在LNB患者中，有24份治疗后的脑脊液样本可用于CXCL13分析。在这些样本的一个子集中测定了新蝶呤浓度。
未经治疗的LNB患者脑脊液样本中的CXCL13浓度（中位数为6480 pg/ml）显著高于非LNB组（中位数<7.8 pg/ml）、病毒性CNS感染样本（中位数<7.8 pg/ml）或非感染性神经炎症性疾病患者的样本（中位数<7.8 pg/ml）。使用415 pg/ml的临界值对这些样本中LNB的诊断敏感性为100%，特异性为99.7%。脑脊液CXCL13中位数浓度从治疗前的16770 pg/ml显著下降至治疗后的109 pg/ml。未经治疗的LNB患者脑脊液新蝶呤浓度显著高于非LNB组。使用10.6 nM的新蝶呤浓度作为临界值对LNB的诊断敏感性为88.6%，特异性为65.0%。脑脊液新蝶呤浓度随治疗有统计学显著下降。
这些结果清楚地表明，脑脊液CXCL13水平的高度升高与未经治疗的LNB密切相关。CXCL13的表现优于新蝶呤，似乎是区分LNB与病毒性CNS感染及其他神经炎症性疾病的优秀生物标志物。
