宏基因组二代测序在伴有中枢神经系统受累儿童噬血细胞综合征中的应用价值

Value of metagenomic next-generation sequencing in children with hemophagocytic syndrome with central nervous system involvement

摘要:

目的 探究宏基因组二代测序（metagenomic next-generation sequencing，mNGS）技术检测伴有中枢神经系统受累的噬血细胞综合征患儿颅内EB病毒（Epstein-Barr virus，EBV）感染的应用价值及临床意义。 方法 回顾性分析30例伴有中枢神经系统受累的噬血细胞综合征患儿的脑脊液mNGS结果，与脑脊液EBV-DNA定性检测、血清EBV抗体谱检测结果进行比较，以治疗前后血清EBV-DNA拷贝数变化反映针对性治疗效果。 结果 脑脊液mNGS EBV检测阳性率为100%（30/30），高于脑脊液EBV-DNA定性检测阳性率（10%，3/30；P<0.001），与血清EBV抗体谱检测阳性率（93%，28/30）比较差异无统计学意义（P>0.05）。中位mNGS EBV检出序列数为2 400，治疗前血清EBV-DNA拷贝数与EBV检出序列数呈中度正相关（r_s=0.693，P<0.001）。多元线性回归分析结果显示，治疗前血清EBV-DNA拷贝数越高，脑脊液mNGS EBV检出序列数越高（P<0.05）。 结论 EBV相关噬血细胞综合征容易诱发EBV感染引起的病毒性脑炎，mNGS可以显著提高脑脊液EBV检测的阳性率，协助临床诊断。

Abstract:

Objective To study the value of metagenomic next-generation sequencing (mNGS) in detecting intracranial Epstein-Barr virus (EBV) infection in children with hemophagocytic syndrome (HPS) with central nervous system involvement. Methods A retrospective analysis was performed for the cerebrospinal fluid mNGS results of 30 HPS children with central nervous system involvement, which were compared with the results of cerebrospinal fluid EBV-DNA detection and serum EBV antibody profile. The change in serum EBV-DNA copy number after treatment was used to evaluate the efficacy of targeted therapy. Results The positive rate of EBV in cerebrospinal fluid determined by mNGS was significantly higher than that of EBV-DNA in cerebrospinal fluid (100% vs 10%, P<0.001) and had no significant difference from the positive rate of serum EBV antibody profile (100% vs 93%, P>0.05). The median number of sequences determined by mNGS was 2 400, and serum EBV-DNA copy number before treatment was moderately positively correlated with the number of EBV sequences (rs=0.693, P<0.001). The multiple linear regression analysis showed that the number of sequences determined by mNGS in cerebrospinal fluid increased with the increase in serum EBV-DNA copy number before treatment (P<0.05). Conclusions EBV-associated HPS often results in EBV-infected viral encephalitis, and mNGS can significantly increase the detection rate of EBV in cerebrospinal fluid, which may help with clinical diagnosis.