Department of Pediatric Immunology and Infectious Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
J Clin Immunol. 2019 Aug;39(6):577-591. doi: 10.1007/s10875-019-00656-x. Epub 2019 Jun 28.
As the application of next generation sequencing (NGS) is moving to earlier stages in the diagnostic pipeline for primary immunodeficiencies (PIDs), re-evaluation of its effectiveness is required. The aim of this study is to systematically review the diagnostic yield of NGS in PIDs.
PubMed and Embase databases were searched for relevant studies. Studies were eligible when describing the use of NGS in patients that had previously been diagnosed with PID on clinical and/or laboratory findings. Relevant data on study characteristics, technological performance and diagnostic yield were extracted.
Fourteen studies were eligible for data extraction. Six studies described patient populations from specific PID subcategories. The remaining studies included patients with unsorted PIDs. The studies were based on populations from Italy, Iran, Turkey, Thailand, the Netherlands, Norway, Saudi Arabia, Sweden, the UK, and the USA. Eight studies used an array-based targeted gene panel, four used WES in combination with a PID filter, and two used both techniques. The mean reported reading depth ranged from 98 to 1337 times. Five studies described the sensitivity of the applied techniques, ranging from 83 to 100%, whereas specificity ranged from 45 to 99.9%. The percentage of patients who were genetically diagnosed ranged from 15 to 79%. Several studies described clinical implications of the genetic findings.
NGS has the ability to contribute significantly to the identification of molecular mechanisms in PID patients. The diagnostic yield highly depends on population and on the technical circumstances under which NGS is employed. Further research is needed to determine the exact diagnostic yield and clinical implications of NGS in patients with PID.
随着下一代测序（NGS）在原发性免疫缺陷（PID）的诊断管道的早期阶段的应用，需要重新评估其有效性。本研究的目的是系统地综述 NGS 在 PID 中的诊断效果。
在 PubMed 和 Embase 数据库中搜索相关研究。当描述在临床和/或实验室发现先前诊断为 PID 的患者中使用 NGS 时，研究是合格的。提取了关于研究特征、技术性能和诊断效果的相关数据。
有 14 项研究符合数据提取标准。6 项研究描述了特定 PID 亚类别的患者人群。其余的研究包括未分类 PID 的患者。这些研究基于来自意大利、伊朗、土耳其、泰国、荷兰、挪威、沙特阿拉伯、瑞典、英国和美国的人群。8 项研究使用基于阵列的靶向基因面板，4 项研究使用 WES 结合 PID 滤波器，2 项研究同时使用这两种技术。报告的平均读取深度从 98 到 1337 次不等。5 项研究描述了所应用技术的敏感性，范围从 83%到 100%，而特异性范围从 45%到 99.9%。基因诊断的患者比例从 15%到 79%不等。一些研究描述了遗传发现的临床意义。
NGS 有能力显著促进 PID 患者分子机制的识别。诊断效果高度依赖于人群以及 NGS 应用的技术环境。需要进一步研究以确定 NGS 在 PID 患者中的确切诊断效果和临床意义。
