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Publications

Journal Article Epublish

PubMed: 41727503 DOI: 10.3389/fimmu.2026.1742811

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.

Front Immunol 17:1742811

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

Affiliations

  • Research Centre for Medical Genetics, Moscow, Russia.
  • Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
  • Federal State Autonomous Institution (FSAI) «National Medical Research Center for Children's Health» of the Ministry of Health of the Russian Federation, Moscow, Russia.
  • S.V.Ochapovsky Regional Clinical Hospital â„–1, Krasnodar, Russia.
  • Republican Medical Genetic Centre, Ufa, Russia.
  • Diagnostic Centre (Medical Genetic), Saint-Petersburg, Russia.
  • National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia.
  • Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russia.
  • Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia.
  • Rostov State Medical University, Rostov-on-Don, Russia.
  • Clinical Diagnostic Centre «Mother and Child Healthcare», Yekaterinburg, Russia.
  • Morozovskaya Children's City Clinical Hospital of the Moscow City Health Department, Moscow, Russia.
  • Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
  • Pediatric Oncology & Hematology Center, Regional Children's Hospital, Yekaterinburg, Russia.
  • Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia.

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.

MeSH

Cells, Parturition, Infant, Newborn, Neonatal Screening, Severe Combined Immunodeficiency, Immune System Diseases, Agammaglobulinemia, Therapeutics, B-Lymphocytes