Thanh T T, Casals-Pascual C, Ny N T H, Ngoc N M, Geskus R, Nhu L N T, Hong N T T, Duc D T, Thu D D A, Uyen P N, Ngoc V B, Chau L T M, Quynh V X, Hanh N H H, Thuong N T T, Diem L T, Hanh B T B, Hang V T T, Oanh P K N, Fischer R, Phu N H, Nghia H D T, Chau N V V, Hoa N T, Kessler B M, Thwaites G, Tan L V
Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
Department of Clinical Microbiology, Hospital Clínic de Barcelona, CDB, Barcelona, Spain; ISGlobal Barcelona, Institute for Global Health, Barcelona, Spain.
Clin Microbiol Infect. 2020 Jul 11;27(5):724-30. doi: 10.1016/j.cmi.2020.07.006.
Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome.
We applied liquid chromatography tandem mass spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with and without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam.
In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and virus/antibody-mediated encephalitis), with sensitivity of 0.88 (95% confident interval (CI), 0.77-0.94), specificity of 0.91 (95% CI, 0.88-0.94) and diagnostic odds ratio of 73.8 (95% CI, 31.8-171.4). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under the receiver operating characteristics curve, 0.96; 95% CI, 0.93-0.99). Data are available via ProteomeXchange with identifier PXD020510.
LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.
中枢神经系统（CNS）感染是全球发病和死亡的常见原因。我们旨在发现能够快速、准确识别感染可能病因的蛋白质生物标志物，这对临床管理和改善预后至关重要。
我们对一组有或无CNS感染的成人的45份脑脊液（CSF）样本应用液相色谱串联质谱法，以发现潜在的诊断生物标志物。然后，我们在越南一家转诊医院连续收治的364例接受治疗的成人CNS感染独立队列中验证了所选生物标志物候选物的诊断性能。
在发现队列中，我们确定了脂质运载蛋白2（LCN2）是除结核性脑膜炎外细菌性脑膜炎（BM）的潜在生物标志物。验证队列分析表明，LCN2可将BM与其他CNS感染（包括结核性脑膜炎、隐球菌性脑膜炎和病毒/抗体介导的脑炎）区分开来，敏感性为0.88（95%置信区间（CI），0.77 - 0.94），特异性为0.91（95%CI，0.88 - 0.94），诊断比值比为73.8（95%CI，31.8 - 171.4）。LCN2的表现优于全球常规护理中常用的其他CSF标志物（白细胞、葡萄糖、蛋白质和乳酸）。LCN2、CSF白细胞、葡萄糖、蛋白质和乳酸的组合对BM的诊断性能最高（受试者工作特征曲线下面积，0.96；95%CI，0.93 - 0.99）。数据可通过ProteomeXchange获得，标识符为PXD020510。
LCN2是一种敏感且特异的生物标志物，可用于区分BM与其他多种CNS感染。需要进行前瞻性研究以评估LCN2在CNS感染诊断和管理中的诊断效用。
