‘Combined TREC/KREC screening improves early detection of severe actionable inborn errors of immunity’

Štítky

Markéta Bloomfield, Eva Hlaváčková, Helena Schneiderová, Marek Turnovec, Lukáš Tichý, Zbyněk Čech, Petr Chrastina, Lenka Dvořáková, Karolína Pešková, Renata Formánková, Petr Říha, Marcela Vlková, Petr Bejdák, Magdaléna Havlišová, Eva Froňková, Tomáš Kalina, Viktor Bíly, Dita Říčná, Hana Grombiříková, Petr Sedláček, Jiří Litzman, Tomáš Freiberger, Anna Šedivá, Adam Klocperk | Pediatric Allergy and Immunology | May 2025 | IF = 4.5 | doi

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.