Journal Article

TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan

Takahashi, Yoshiyuki, Tanaka, Makito, Ito, Tsuyoshi, Nakamura, Fumiko, Tsuge, Ikuya, Kojima, Daiei, Saito, Akiko, Muramatsu, Hideki, Ito, Yasuhiko, Kataoka, Shinsuke, Ito, Tetsuya, Nakajima, Yoko, Ohashi, Naoki, Morihana, Eiji, Kojima, Seiji, Okuno, Yusuke, Sakai, Yoshimi, Ueda, Kazuto, Wakamatsu, Manabu, Tanaka, Taihei

2022

Overview

Purpose The aim of this study is to evaluate the usefulness of T cell receptor excision circle (TREC) and/or kappa-deleting recombination excision circle (KREC) measurements integrated with diagnostic next-generation sequencing (NGS) analysis using a severe combined immunodeficiency (SCID) newborn screening (NBS) program. Methods TREC and/or KREC values were measured in 137,484 newborns between April 2017 and December 2021 using EnLite TREC ( n  = 80,791) or TREC/KREC kits ( n  = 56,693). For newborns with positive screening results, diagnostic NGS analysis was performed with a 349-gene panel to detect genetic mutations associated with primary immunodeficiencies (PIDs). Results A total of 145 newborns (0.11%) had abnormal TREC and/or KREC values, and a genetic diagnosis was established in 2 patients with SCID (1 in 68,742 newborns) (IL2RG-SCID and reticular dysgenesis) and 10 with non-SCID PIDs with T and/or B cell deficiencies (1 in 13,748 newborns) using NGS analysis. Furthermore, TREC values of 2849 newborns were measured and confirmed the significant correlation between the results of both TREC and TREC/KREC kits ( P  < 0.001) and naïve T cell counts. Conclusions We performed the first large-scale TREC and TREC/KREC NBS programs in Japan. Our NBS programs followed by the diagnostic NGS analysis for newborns with abnormal TREC and/or KREC values are useful for the early identification and rapid molecular evaluation of not only SCID but also different non-SCID PIDs.

• Publisher: Springer US,Springer Nature B.V
• Subject: B-lymphocytes / Biomedical and Life Sciences / Biomedicine / circular DNA / DNA / excision / Genetic screening / High-Throughput Nucleotide Sequencing / Humans / Immune system / Immunology / immunosuppression / Infant, Newborn / Infectious Diseases / Internal Medicine / Japan / Lymphocytes T / Medical Microbiology / Medical screening / Neonatal Screening - methods / Neonates / Next-generation sequencing / Original Article / Primary immunodeficiencies / Receptors, Antigen, T-Cell - genetics / Recombination / Severe combined immunodeficiency / Severe Combined Immunodeficiency - diagnosis / Severe Combined Immunodeficiency - genetics / T cell receptors / T-Lymphocytes