Diagnostic yield of next-generation sequencing in suspect primary immunodeficiencies diseases: a systematic review and meta-analysis

Abstract 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.