Perlejewski Karol, Pawełczyk Agnieszka, Bukowska-Ośko Iwona, Rydzanicz Małgorzata, Dzieciątkowski Tomasz, Paciorek Marcin, Makowiecki Michał, Caraballo Cortés Kamila, Grochowska Marta, Radkowski Marek, Laskus Tomasz
Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, Warsaw, Poland.
Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Open Forum Infect Dis. 2020 Oct 7;7(11):ofaa468. doi: 10.1093/ofid/ofaa468. eCollection 2020 Nov.
It has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics.
CSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics.
Autoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR.
We detected the presence of HSV, TTV, and genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.
据报道,病毒介导的脑组织损伤可导致自身免疫性脑炎(AE),其特征为存在针对神经元表面抗原的抗体。在本研究中,我们使用逆转录聚合酶链反应(RT-PCR)/PCR和鸟枪法宏基因组学研究AE患者脑脊液(CSF)中病毒的存在情况。
收集200例脑炎患者的CSF样本,检测其针对抗谷氨酸受体(NMDAR)、接触蛋白相关蛋白2(CASPR2)、谷氨酸受体(AMPA1/2型)、富含亮氨酸的胶质瘤失活蛋白1(LGI1)、二肽基肽酶样蛋白6(DPPX)和GABA B受体的抗体,对检测为阳性的样本进一步采用实时RT-PCR/PCR检测常见病毒性神经感染,并进行基于DNA和RNA的鸟枪法宏基因组学分析。
在8例个体(占所有脑炎患者的4%)的CSF中检测到针对神经元细胞的自身抗体:7例(3.5%)为抗NMDAR,1例(0.5%)为抗GABA B。RT-PCR/PCR在1例患者中分别鉴定出人疱疹病毒1型(HSV-1;300拷贝/毫升)和某属代表病毒(550拷贝/毫升)。通过宏基因组学分析在另1例患者中发现了细小病毒B19,并用特异性PCR证实了其存在。
我们在8例AE患者中的3例CSF样本中检测到HSV、细小病毒B19和某属病毒的存在。这些发现支持病毒参与该疾病发病机制的观点。