Kim Kristin Falk , Ligia Abrante Cabrera , Ralf Junker , Frank Leypoldt , Michael P. Malter , Robert Markewitz , Makbule Senel , Hayrettin Tumani , Klaus-Peter Wandinger , Uwe K. Zettl , Justina Dargvainiene
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引用次数: 0
Abstract
Objectives
Herpes simplex virus 1 encephalitis (HSE) is the most common infectious encephalitis in developed countries. We aimed to evaluate the association of serum neurofilament light chain (sNfL) with disease severity, outcome and secondary anti-neuronal autoantibodies in a retrospective cohort study.
Methods
We retrospectively identified 30 patients with HSE and 132 controls (bacterial meningoencephalitis BM n = 27, non-bacterial meningitis NBM n = 33, healthy controls = 72). sNfL concentration was tested in all available samples (N = 231) using single molecule array (SiMoA) technology. Screening for secondary anti-neuronal autoantibodies was performed using rat brain immunohistochemistry, cell-based assays for anti-neuronal surface antibodies and indirect immunofluorescence with non-permeabilized rat hippocampal neuronal cultures.
Results
Patients with HSE and BM had higher sNfL levels than NBM and healthy controls. Within the HSE group, higher onset sNfL levels were associated with need for mechanical ventilation and poorer outcome measured by modified Rankin Scale. Increased sNFL levels in follow-up samples (24 days after HSE onset, 95 % CI 15–33) were associated with development of secondary anti-neuronal autoantibodies.
Discussion
Our results suggest sNfL as a potential biomarker of neuroaxonal damage in HSE with the potential to identify patients at risk of developing secondary anti-neuronal autoantibodies, which might lead to secondary autoimmunity of central nervous system. Future studies are needed to evaluate diagnostic values and establish suitable cut-offs.
目的:单纯疱疹病毒1型脑炎(HSE)是发达国家最常见的感染性脑炎。在一项回顾性队列研究中,我们旨在评估血清神经丝轻链(sNfL)与疾病严重程度、转归和继发性抗神经元自身抗体的关系。方法:回顾性分析30例HSE患者和132例对照(细菌性脑膜脑炎患者27例,非细菌性脑膜脑炎患者33例,健康对照72例)。采用单分子阵列(SiMoA)技术检测所有可用样品(N = 231)的sNfL浓度。利用大鼠脑免疫组织化学、细胞抗神经元表面抗体和非渗透大鼠海马神经元培养物的间接免疫荧光进行二次抗神经元自身抗体筛选。结果:HSE和BM患者的sNfL水平高于NBM和健康对照组。在HSE组中,较高的sNfL水平与机械通气需求和较差的预后相关。随访样本中sNFL水平升高(HSE发病后24天,95% CI 15-33)与继发性抗神经元自身抗体的发展相关。讨论:我们的研究结果表明,sNfL是HSE神经轴突损伤的潜在生物标志物,有可能识别有发生继发性抗神经元自身抗体风险的患者,这可能导致中枢神经系统的继发性自身免疫。未来的研究需要评估诊断价值并建立合适的截止值。
期刊介绍:
The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.