Department of Dermatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
The First Clinical College of Guangzhou Medical University, Guangzhou, 510180, China.
Clin Exp Med. 2024 Jun 18;24(1):131. doi: 10.1007/s10238-024-01392-2.
To determine the diagnostic yield of Next-generation sequencing (NGS) in suspect Primary Immunodeficiencies Diseases (PIDs). This systematic review was conducted following PRISMA criteria. Searching Pubmed and Web of Science databases, the following keywords were used in the search: ("Next-generation sequencing") OR "whole exome sequencing" OR "whole genome sequencing") AND ("primary immunodeficiency disease" OR "PIDs"). We used STARD items to assess the risk of bias in the included studies. The meta-analysis included 29 studies with 5847 patients, revealing a pooled positive detection rate of 42% (95% CI 0.29-0.54, P < 0.001) for NGS in suspected PID cases. Subgroup analyses based on family history demonstrated a higher detection rate of 58% (95% CI 0.43-0.71) in patients with a family history compared to 33% (95% CI 0.21-0.46) in those without (P < 0.001). Stratification by disease types showed varied detection rates, with Severe Combined Immunodeficiency leading at 58% (P < 0.001). Among 253 PID-related genes, RAG1, ATM, BTK, and others constituted major contributors, with 34 genes not included in the 2022 IUIS gene list. The application of NGS in suspected PID patients can provide significant diagnostic results, especially in patients with a family history. Meanwhile, NGS performs excellently in accurately diagnosing disease types, and early identification of disease types can benefit patients in treatment.
为了确定下一代测序（NGS）在疑似原发性免疫缺陷病（PID）中的诊断产量。本系统评价按照 PRISMA 标准进行。通过搜索 Pubmed 和 Web of Science 数据库，在搜索中使用了以下关键词：（“下一代测序”）或“全外显子组测序”或“全基因组测序”）和（“原发性免疫缺陷病”或“PID”）。我们使用 STARD 项目来评估纳入研究的偏倚风险。荟萃分析包括 29 项研究，涉及 5847 名患者，结果显示，在疑似 PID 病例中，NGS 的汇总阳性检出率为 42%（95%CI 0.29-0.54，P<0.001）。基于家族史的亚组分析显示，有家族史的患者检测率较高，为 58%（95%CI 0.43-0.71），而无家族史的患者检测率为 33%（95%CI 0.21-0.46）（P<0.001）。按疾病类型分层显示出不同的检出率，其中严重联合免疫缺陷症最高，为 58%（P<0.001）。在 253 个 PID 相关基因中，RAG1、ATM、BTK 等构成了主要贡献者，其中 34 个基因不在 2022 年 IUIS 基因列表中。NGS 在疑似 PID 患者中的应用可以提供重要的诊断结果，特别是在有家族史的患者中。同时，NGS 在准确诊断疾病类型方面表现出色，早期识别疾病类型可以使患者受益于治疗。
