Results of newborn screening for inborn errors of immunity in the healthcare system of the Northwestern Federal District of Russian Federation in 2023-2024

The newborn screening program (NBS) plays a critical role in the development of the healthcare system of the Russian Federation. Since 2023, the Order No. 274n “On the approval of the Procedure for providing medical care to patients with congenital and/or hereditary diseases” has extended the scope of neonatal screening. The expanded newborn screening (ENS) includes detection of 36 nosological conditions. Among these, inborn errors of immunity (IEI) represent a significant and still extending group of genetic disorders characterized by increased susceptibility to infections due to underlying immunopathological mechanisms. At the initial stage, quantitative determination of T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) is performed for all newborns in order to identify individuals at risk and initiate confirmatory diagnostics. This approach enables the detection of IEI before the onset of clinical symptoms. This article presents and analyzes the results of ENS program for IEI conducted at the Northwestern Federal District (NWFD) during the period from 2023 to 2024. Over this two-year period, a total of 209,741 newborns were screened at the NWFD. Among them, 818 newborns (0.39% of those screened) were classified as high-risk IEI cases. The immunodeficiency states were identified for 45 children as based on immunophenotyping of peripheral blood lymphocytes (IFT), and genetic causes of the condition were confirmed in 49% of these cases. Statistical analysis revealed associations between gestational age and birth weight with TREC levels, and, to lesser extent, with KREC levels. The reference intervals were established for defined subgroups of neonates. These findings highlight the importance of continuous observation of newborns classified as moderate-risk cases. Notably, 9% of all screened individuals were designated as “conditionally healthy,” despite having TREC or KREC values below the lower reference limit. Based on the obtained data, the models for optimizing the screening program for IEI were proposed. These findings contribute to earlier diagnosis and more effective management of patients with immune disorders, as well as enhanced personalization of therapeutic strategies. Establishing population-based reference intervals plays a key role in standardizing methods for diagnostics and monitoring the immune system, thus representing an important step in overall advances of healthcare.