Koopmans Merel M, Brouwer Matthijs C, Geldhoff Madelijn, Seron Mercedes Valls, Houben Judith, van der Ende Arie, van de Beek Diederik
Department of Neurology, Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands.
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands ; The Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam, The Netherlands.
BBA Clin. 2014 Jun;1:44-51. doi: 10.1016/j.bbacli.2014.06.001.
meningitis is the third most common cause of bacterial meningitis and is associated with high rates of mortality and unfavorable outcome.
We analyzed 101 cytokines, chemokines and complement factors in CSF of adult patients with Listeria meningitis included in a prospective cohort study and compared these biomarkers between Listeria meningitis patients and negative controls, and between Listeria meningitis patients with a favorable and an unfavorable outcome.
CSF was available from 26 of 62 (42%) Listeria meningitis patients and 19 negative controls. Fifteen (58%) Listeria meningitis patients had an unfavorable outcome. In Listeria meningitis CSF levels of 51 biomarkers were significantly elevated compared to negative controls after Bonferroni correction. The 11 most significantly elevated (P < .01) biomarkers of unfavorable outcome in Listeria meningitis were markers of T-cell activation (sIL-2Rα, sCD40L and IL-1), interferon-related (IFN-α2, IL-18, CX3CL1, CCL20), markers of complement activation (C3a), and endothelial growth factor related (VEGF, CXCL7).
Our data suggest that T-cell activation, complement activation, interferon- and endothelial growth factor production are important in the immune response to Listeria meningitis, and thereby influence outcome.
Our study provides target pathways for further studies in the pathophysiology of Listeria meningitis.
李斯特菌性脑膜炎是细菌性脑膜炎的第三大常见病因，与高死亡率和不良预后相关。
我们分析了一项前瞻性队列研究中成年李斯特菌性脑膜炎患者脑脊液中的101种细胞因子、趋化因子和补体因子，并比较了这些生物标志物在李斯特菌性脑膜炎患者与阴性对照组之间，以及在预后良好和预后不良的李斯特菌性脑膜炎患者之间的差异。
62例李斯特菌性脑膜炎患者中有26例（42%）提供了脑脊液样本，19例为阴性对照。15例（58%）李斯特菌性脑膜炎患者预后不良。经Bonferroni校正后，与阴性对照组相比，李斯特菌性脑膜炎患者脑脊液中51种生物标志物水平显著升高。李斯特菌性脑膜炎患者预后不良的11种最显著升高（P <.01）的生物标志物是T细胞活化标志物（可溶性白细胞介素-2受体α、可溶性CD40配体和白细胞介素-1）、干扰素相关标志物（干扰素-α2、白细胞介素-18、CX3CL1、CCL20）、补体活化标志物（C3a）和内皮生长因子相关标志物（血管内皮生长因子、CXCL7）。
我们的数据表明，T细胞活化、补体活化、干扰素和内皮生长因子的产生在对李斯特菌性脑膜炎的免疫反应中起重要作用，从而影响预后。
我们的研究为李斯特菌性脑膜炎病理生理学的进一步研究提供了目标途径。
