Nationwide TREC/KREC-based newborn screening and clinical outcomes in Japan
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Nishinosono et al. show that nationwide TREC/KREC newborn screening in Japan demonstrates that large-scale programs can achieve favorable outcomes while revealing practical implementation challenges. Public funding expands coverage, whereas interlaboratory variability highlights the need for standardized cutoffs and repeat-sampling algorithms for equitable nationwide implementation. teaser Large-scale real-world data on T-cell receptor excision circle (TREC)– and κ-deleting recombination excision circle (KREC)–based newborn screening for inborn errors of immunity remain limited. In this nationwide cohort, we evaluated Japan’s program (2020–2025), including 1,380,634 newborns. Of 869 referred infants (0.06%), 40 were diagnosed, including 15 with severe combined immunodeficiency (SCID), 16 with X-linked agammaglobulinemia or other agammaglobulinemias, and nine with severe T cell lymphopenia. After a median follow-up of 18 mo, overall survival was 98%. All infants with SCID survived; 14 underwent hematopoietic cell transplantation with sustained engraftment. Referral rates were 0.04% for TREC and 0.03% for KREC. Repeat sampling was associated with lower referral rates (0.05 vs. 0.56%). Referral rates varied across assay kits and laboratory practices, reflecting interlaboratory heterogeneity in a decentralized screening system. The transition from self-paid to public funding increased coverage from 77.1 to 97.7%. These findings support TREC/KREC-based screening and highlight the
Abstract
Nishinosono et al. show that nationwide TREC/KREC newborn screening in Japan demonstrates that large-scale programs can achieve favorable outcomes while revealing practical implementation challenges. Public funding expands coverage, whereas interlaboratory variability highlights the need for standardized cutoffs and repeat-sampling algorithms for equitable nationwide implementation. teaser Large-scale real-world data on T-cell receptor excision circle (TREC)– and κ-deleting recombination excision circle (KREC)–based newborn screening for inborn errors of immunity remain limited. In this nationwide cohort, we evaluated Japan’s program (2020–2025), including 1,380,634 newborns. Of 869 referred infants (0.06%), 40 were diagnosed, including 15 with severe combined immunodeficiency (SCID), 16 with X-linked agammaglobulinemia or other agammaglobulinemias, and nine with severe T cell lymphopenia. After a median follow-up of 18 mo, overall survival was 98%. All infants with SCID survived; 14 underwent hematopoietic cell transplantation with sustained engraftment. Referral rates were 0.04% for TREC and 0.03% for KREC. Repeat sampling was associated with lower referral rates (0.05 vs. 0.56%). Referral rates varied across assay kits and laboratory practices, reflecting interlaboratory heterogeneity in a decentralized screening system. The transition from self-paid to public funding increased coverage from 77.1 to 97.7%. These findings support TREC/KREC-based screening and highlight the need for standardized algorithms and sustained public funding for equitable nationwide implementation. Graphical Abstract A flowchart depicting the nationwide TREC/KREC newborn screening for Inborn errors of immunity in Japan. Population. Nationwide screening across 32 laboratories from April 2020 to March 2025. 1,380,634 newborns screened. 869 referrals (0.06 percent). Higher referral rates in no-repeat-sampling laboratories. Screening. Detection of IEI by TREC/KREC Screening. 40 confirmed IEI cases. SCID, n equals 15. XLA and other Agammaglobulinemias, n equals 16. Severe T-Cell Lymphopenia (sTCL), n equals 9. Clinical Outcome. Clinical Outcomes of Screened Cohort. Early interventions. All transplanted patients achieved engraftment. SCID Survival 100 percent (15/15 infants with SCID). Implementation Impact. Policy Impact and Laboratory Diversity. Public funding. Coverage by funding framework. 77.1 percent before (self-paid) to 97.7 percent after (public funding). Interlaboratory variability. Referral rates varied across assay kits. Practice heterogeneity identified. http://www.w3.org/1999/xlink float portrait jhi_20260083_ga.webp float GA portrait graphical