mNGS在急性或亚急性脑炎或脑膜炎患者脑脊液中检出的DNA病毒特征及临床意义  

Features and clinical significance of DNA viruses detected by metagenomic Next-generation Sequencing of cerebrospinal fluids in acute or subacute encephalitis or meningitis patients

作　　者：甘周庆 杨露 王翼洁 刘佳[1] 陈灼林 江滢[1] 李敏[1] 彭福华[1] Gan Zhouqing;Yang Lu;Wang Yijie;Liu Jia;Chen Zhuolin;Jiang Ying;Li Min;Peng Fuhua(Department of Neurology,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院神经内科,广州510630

出　　处：《新医学》2020年第5期354-359,共6页Journal of New Medicine

基　　金：广东省自然科学基金(2015A03013167);广州市科技计划项目(201510010251)。

摘　　要：目的分析微生物宏基因组二代测序(mNGS)在急性或亚急性脑炎或脑膜炎患者脑脊液中检出的DNA病毒特征和临床意义。方法对疑诊急性或亚急性脑炎或脑膜炎并接受脑脊液mNGS的病例进行回顾性分析,按照临床诊断分组并比较各组检出的DNA病毒种类、特异序列水平[每1 M序列中的比对序列数(RPM)]和传统病毒病原学检查结果。结果 160例疑诊急性或亚急性脑炎或脑膜炎的病例分别有30例(18.8%)、85例(53.1%)和45例(28.1%)的临床诊断为病毒性脑炎或脑膜炎(不能区分DNA病毒和RNA病毒)、其他感染性脑炎或脑膜炎(细菌、真菌或寄生虫)和非感染性脑炎或脑膜炎(免疫炎性、肿瘤等),这3组中分别有8例(26.7%)、30例(35.3%)和8例(17.8%)检出DNA病毒。病毒性脑炎或脑膜炎组mNGS检出的病毒均为疱疹病毒,以单纯疱疹病毒1型、水痘-带状疱疹病毒和巨细胞病毒最常见,其RPM有很高的,但大部分均很低,去除RPM≥100的数据后,其平均RPM与非感染性脑膜炎组和其他感染性脑膜炎或脑膜炎组比较差异无统计学意义(P> 0.05)。除了1例有传统病毒病原学阳性结果和1例有很高的RPM支持其致病性,其他均无传统病毒病原学证据支持其致病性;而另外2组可以检出多种DNA病毒,以EB病毒、细环病毒和巨细胞病毒最常见,尤其是其他感染性脑炎或脑膜炎组,它们的平均RPM很低,而且均无传统病毒病原学证据支持其致病性。结论急性或亚急性脑炎或脑膜炎患者的脑脊液中疱疹病毒和细环病毒等DNA病毒较为常见,尤其是感染性疾病中,mNGS有助于其检出和诊断,但对于占多数的RPM较低的结果,是否有致病性及临床意义,仍需结合临床分析作进一步解读。Objective To analyse the features and clinical significance of DNA viruses detected by metagenomic Next-generation Sequencing(m NGS) of cerebrospinal fluids(CSF) in acute or subacute encephalitis or meningitis patients. Methods A retrospective analysis is performed on the cases of acute or subacute encephalitis or meningitis conducted m NGS(based on Illumina Mini Seq system, with reads per million mapped readers(RPM) ≥ 1 as positive for DNA viruses) of CSF, and the viral types and their RPM levels were compared among groups classified according to clinical diagnosis, a composite reference standard. Results Among 160 cases of suspected encephalitis or meningitis, 30 cases(18.8%), 85 cases(53.1%) and 45 cases(28.1%) were classified into viral encephalitis or meningitis(VEM) group, non-viral infectious encephalitis or meningitis(NVIEM) group and non-infectious encephalitis or meningitis(NIEM) group respectively, and DNA viruses were detected in 8 cases(26.7%), 30 cases(35.3%) and 8 cases(17.8%) of the 3 groups respectively. The DNA viruses in VEM group are all herpesviruses, with human alpha-herpesvirus1, human alpha-herpesvirus 3 and cytomegalovirus being the most common, and most of them with low RPM, When excluding data with RPM ≥ 100 of this group, there are no significant statical difference among 3 group(P > 0.05). Viruses in this group all had no evidence of traditional viral etiology to support their pathogenicity, with low RPM levels as well, except for one case with positive results of traditional viral etiology and one case with really high RPM level. In contrast, Estein-Barr virus, Torque teno viruses and cytomegalovirus are most frequently seen in the other 2 groups, especially in NVIEM group, with lower RPM levels and without evidence of traditional viral etiology to support their pathogenicity for all cases. Conclusions DNA viruses like herpesviruses and Torque teno viruses can be commonly seen in CSF of acute or subacute encephalitis or meningitis patients, especially in infectious diseases, m NG

关 键 词：DNA病毒 脑炎 脑膜炎 脑脊液 宏基因组二代测序 临床意义 

分 类 号：R742.9[医药卫生—神经病学与精神病学]