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. 2025 May;36(5):e70100.
doi: 10.1111/pai.70100.

Beyond TREC: Pivotal role of tandem TREC/KREC assay in Czech SCID NBS pilot programme

Markéta Bloomfield  1 , Eva Hlaváčková  2 , Helena Schneiderová  3   4 , Marek Turnovec  5 , Lukáš Tichý  6 , Zbyněk Čech  6 , Petr Chrastina  7 , Lenka Dvořáková  7 , Karolína Pešková  7 , Renata Formánková  8 , Petr Říha  8 , Marcela Vlková  2 , Petr Bejdák  2 , Magdaléna Havlišová  1 , Eva Froňková  8   9 , Tomáš Kalina  8   9 , Viktor Bíly  4   10 , Dita Říčná  10 , Hana Grombiříková  4   10 , Petr Sedláček  8 , Jiří Litzman  2 , Tomáš Freiberger  4   10 , Anna Šedivá  1 , Adam Klocperk  1
Affiliations

Beyond TREC: Pivotal role of tandem TREC/KREC assay in Czech SCID NBS pilot programme

Markéta Bloomfield et al. Pediatr Allergy Immunol. 2025 May.

Abstract

Background: Severe combined immunodeficiency (SCID) is a fatal but treatable inborn error of immunity (IEI). Newborn screening (NBS) using T-cell receptor excision circles (TREC) has been adopted globally, with very few countries incorporating kappa recombination excision circles (KREC) to also detect early B-cell development disorders, such as X-linked agammaglobulinemia (XLA).

Objective: To evaluate the effectiveness of a 2-year pilot SCID NBS program in the Czech Republic, emphasising the utility of combined TREC/KREC screening.

Methods: Between January 2022 and December 2023, a dual TREC/KREC NBS pilot was conducted across the Czech Republic, alongside spinal muscular atrophy (SMA) screening. Approximately 200,000 newborns were screened using quantitative real-time PCR on dried blood spots collected 48-72 h after birth.

Results: The pilot referred 58 newborns, identifying 21 cases of IEI, including two SCID cases, with an overall incidence of TREC/KREC screenable IEI of 10.5/100,000 newborns. SCID incidence was 1/100,000. KREC screening proved invaluable, detecting 10 cases of congenital agammaglobulinemia including novel non-XLA forms, which increased the estimated incidence of agammaglobulinemia in the Czech Republic sixfold. Over one-third of low KREC results were linked to maternal immunosuppression.

Conclusion: The Czech pilot demonstrated the effectiveness of integrated TREC/KREC NBS in detecting both T- and B-cell immunodeficiencies. As of 2024, SCID and SMA screening are included in the nationwide NBS, with KREC screening significantly improving early detection of B-cell disorders.

Keywords: IGLL1; KREC; SCID; TREC; XLA; agammaglobulinemia; dried blood spot; screening; severe combined immunodeficiency.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Numbers of tested samples and identified/referred neonates.
See this image and copyright information in PMC

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