First 2-year experience of nationwide newborn screening for severe forms of T and B cell immunodeficiency: 2.3 million newborns analyzed using TREC and KREC in Russia
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: Here, we present the results of a nationwide newborn screening (NBS) program in Russia, covering over 2.3 million newborns and employing TREC and KREC quantification to improve the identification of severe forms of T and/or B cell immunodeficiencies and enable early treatment initiation. Methods: A two-tier PCR testing strategy was used to define the screen-positive cohort, followed by confirmatory flow cytometry and genetic diagnostics, including fluorescent in situ hybridization (FISH) and whole-exome sequencing (WES). Results: A total of 191 patients were diagnosed with defined forms of primary immunodeficiencies (PID), encompassing several groups of inborn errors of immunity (IEI): severe combined immunodeficiency (SCID), agammaglobulinemia, combined immunodeficiency less severe than SCID, and syndromic forms of PID. The overall birth prevalence of severe forms of T and/or B cell immunodeficiencies was 1 in 12,298 live births (95%CI: 1:10,672-1:14,247), corresponding to 8.13 cases per 100,000 newborns (95%CI: 7.02-9.37). Although the positive predictive value of KREC-based screening was relatively low, its use enabled the detection of a substantial proportion of patients with syndromic forms of PID, including Nijmegen breakage syndrome and ataxia-telangiectasia, along with various forms of agammaglobulinemia. Interestingly, 16% of diagnosed newborns had a positive family history, often with previously undiagnosed affected siblings or parents. Additionally, a considerable number of newborns detected by NBS presented with syndromic disorders not currently classified as IEI, suggesting potential avenues for future expansion of the IEI list. Discussion: Importantly, early diagnosis through NBS allowed for the timely initiation of disease-specific treatments, including hematopoietic stem cell transplantation (HSCT), immunoglobulin replacement therapy, and targeted immunosuppressive or supportive care strategies. Early intervention may reduce the risk of severe infections, improve neurodevelopmental outcomes, and prevent irreversible organ damage or malignancies in predisposed syndromes. Overall, our study demonstrates the effectiveness of large-scale implementation of TREC/KREC-based NBS in identifying a broad spectrum of immunodeficiencies and highlights future directions for improving NBS algorithms, follow-up protocols, and individualized medical management for affected infants.
Source: Frontiers in Immunology
Authors: Andrey Marakhonov, Anna Mukhina, Irina Efimova, Natalia Balinova, Maria Ampleeva, Anastasia Bobreshova, Yulia Rodina, Dmitry Pershin, Viktoriia Zabnenkova, Oxana Ryzhkova, Zhanna Markova, Nadezhda Shilova, Ilya Zhanin, Kirill Savostyanov, Svetlana Matulevich, Fanil Bilalov, Alexander Koroteev, Andrey Donnikov, Dmitry Trofimov, Tatyana Bairova, Gulnara Seitova, Sergei Mordanov, Elena Nikolaeva, Zareta Esmurzieva, Elena Skorobogatova, Lyudmila Olkhova, Larisa Vakhonina, Daria Kostenko, Gleb Bronin, Sergey Zimin, Tatiana Bykova, Dmitry Balashov, Rena Zinchenko, Nikolai Grachev, Sergey Voronin, Anna Shcherbina, Sergey Kutsev
Institutions: Research Centre for Medical Genetics, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of the Russian Federation, Scientific Center of Family Health Problems and Human Reproduction, Tomsk National Research Medical Center, Rostov State Medical University, Pirogov Russian National Research Medical University, Russian Children's Clinical Hospital, First Pavlov State Medical University of St. Petersburg
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7127985952