RESULTS OF NEWBORN SCREENING FOR INBORN ERRORS OF IMMUNITY IN THE HEALTHCARE SYSTEM OF THE NORTHWESTERN FEDERAL DISTRICT OF THE RUSSIAN FEDERATION FOR 2023-2024



Cite item

Full Text

Abstract

Abstract

The newborn screening program (NBS) plays a critical role in the development of the healthcare system of the Russian Federation. Since 2023, Order No. 274n “On the approval of the Procedure for providing medical care to patients with congenital and/or hereditary diseases” has expanded the scope of neonatal screening. Expanded newborn screening (ENS) now includes detection of 36 nosological conditions.

Among these, inborn errors of immunity (IEI) represent a significant and expanding 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 conducted for all newborns 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 for IEI conducted in 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 in the NWFD. Among them, 818 newborns (0.39% of those screened) were classified as high-risk for IEI. Cases of immunodeficiency were identified for 45 children 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 a lesser extent with KREC levels. Reference intervals were established for defined neonatal subgroups. The findings highlight the importance of continued observation of newborns classified as moderate-risk. 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, models for optimizing the screening program for IEI were proposed. This, in turn, contributes 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 diagnosing and monitoring the immune system, representing an important step in the overall advancement of healthcare.

 

About the authors

Anastasiia Lobenskaya

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: lobenskaya@mail.ru
ORCID iD: 0000-0002-6399-2962
Scopus Author ID: 57217072426

Clinical laboratory diagnostics doctor, head of Biochemical laboratory Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)

Russian Federation, 194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Anastasia Petrichenko

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: AKPetrich.ko@gmail.com
ORCID iD: 0000-0002-3564-4688
SPIN-code: 2363-8850

Clinical laboratory diagnostics doctor, Biochemical laboratory Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)

Russian Federation, 194044,Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Tanzila Evloeva

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: evloeva.tanzila94@mail.ru
ORCID iD: 0009-0005-8530-7830

Clinical laboratory diagnostics doctor, Biochemical laboratory Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)

Russian Federation, 194044,Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Anastasia Kruglikova

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: a.a.kruglikova@yandex.ru
ORCID iD: 0000-0002-3809-7229
SPIN-code: 3338-2299
Scopus Author ID: 54385447000

PhD, biologist, Biochemical Laboratory Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
Russian Federation, 194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Elena Serebryakova

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: el.a.serebryakova@mail.ru
ORCID iD: 0000-0001-5602-0156
SPIN-code: 9819-8823
Scopus Author ID: 57194720059

Geneticist, head of the Consultative department, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)

Russian Federation, 194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Elena Yalfimova

Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia

Email: yal-lena@yandex.ru
ORCID iD: 0009-0007-9405-653X
SPIN-code: 5649-4471

Candidate of Medical Sciences, Deputy Chief Physician for Clinical Expertise Work, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)

 

Russian Federation, 194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5

Andrey Marakhonov

Federal State Budgetary Institution of Science “Medical and Genetic Research Center named after Academician N.P. Bochkov" (MGNC)

Email: marakhonov@generesearch.ru
ORCID iD: 0000-0002-0972-5118
SPIN-code: 6803-9072
Scopus Author ID: 24559127100

PhD, Head of the Laboratory of Hereditary Achievements of Immunity, Medical and Genetic Research Center
 
 
 
				                	Russian Federation, 							115522, Russian Federation, Moscow, st. Moskvorechye, 1						

											
Margarita Massalskaya

												Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia						

														Email: bezdna86@list.ru
				                	ORCID iD: 0009-0004-3428-2349
				                																			                								
biologist, biochemical laboratory, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
				                	Russian Federation, 							194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5
						

											
Kseniia Shedova

												Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia						

														Email: shedovaksen@gmail.com
				                	ORCID iD: 0009-0002-7093-8291
				                																			                								
Clinical laboratory diagnostics doctor, Biochemical laboratory, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
				                	Russian Federation, 							194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5
						

											
Anastasia Vechkasova

												Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia						

														Email: vechkasova.nastia@mail.ru
				                	ORCID iD: 0009-0004-8775-9630
				                	SPIN-code: 2642-3514
							Scopus Author ID: 58532200600
											                								
Geneticist, Consultative Department, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
				                	Russian Federation, 							194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5
						

											
Antonina Morozova

												Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia						

														Email: amor2703@gmail.com
				                	ORCID iD: 0009-0008-2325-611X
				                																			                								
Biologist, Biochemical Laboratory, Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
				                	Russian Federation, 							194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5
						

											
Alexander Koroteev

												Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center), Saint-Petersburg, Russia						

														Email: alexkoroteev@mail.ru
				                	ORCID iD: 0000-0002-1568-3217
				                	SPIN-code: 8702-6057
							Scopus Author ID: 57211485833
											                								
Candidate of Medical Sciences, Chief Physician of the Saint-Petersburg State Medical Diagnostic Center (Genetic Medical Center)
Candidate of Medical Sciences, 
				                	Russian Federation, 							194044, Russian Federation, Saint-Petersburg, Tobolskaiia st. 5
						

											
I. A. Tuzankina

												Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences						

							Author for correspondence.
							Email: ituzan@yandex.ru
				                	ORCID iD: 0000-0001-7496-0950
				                	SPIN-code: 8480-3628
							Scopus Author ID: 6507111269
											                								
PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Main Research Associate, Research Institute of Immunology and Physiology; Leading Research Associate, Institute of Chemical Engineering, B. Yeltsin Ural Federal University
				                	Russian Federation, 							620078, Russian Federation, Yekaterinburg, Pervomayskaya St., 106						

									

						

															
References

						

							

								
    
																			
  1. Voronin S.V., Kutsev S.I. Neonatal screening for hereditary diseases in Russia: yesterday, today, and tomorrow. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training, 2022, Vol. 10, no. 4, pp. 34–39. (In Russ.)] doi: 10.33029/2308-2402-2022-10-4-34-39
    2. 
																			
  2. Tangye S.G., Al-Herz W., Bousfiha A., Chatila T., Cunningham-Rundles C., Etzioni A., Franco J.L., Holland S.M., Klein C., Morio T., Ochs H.D., Oksenhendler E., Picard C., Puck J., Torgerson T.R., Casanova J.L., Sullivan K.E. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee // J. Clin. Immunol. 2020. Vol. 40, no. 1., pp. 24–64. doi: 10.1007/s10875-019-00737-x
    3. 
																			
  3. Kuzmenko N.B., Shcherbina A.Yu. Classification of primary immunodeficiencies as a reflection of modern ideas about their pathogenesis and therapeutic approaches. Russian Journal of Pediatric Hematology and Oncology., 2017, Vol. 4, no. 3, pp. 51-57. (In Russ.)] doi: 10.17650/2311-1267-2017-4-3-51-57
    4. 
																			
  4. Cornel M.C., Rigter T., Weinreich S.S., Burgard P., Hoffmann G.F., Lindner M., Loeber J.G., Rupp K., Taruscio D., Vittozzi L. A framework to start the debate on neonatal screening policies in the EU: an Expert Opinion Document // European Journal of Human Genetics. 2014. Vol. 22, no. 1, pp. 12–17. doi: 10.1038/ejhg.2013.90
    5. 
																			
  5. Gordukova M.A., Korsunsky I.A., Chursinova Yu.V., Byakhova M.M., Oscorbin I.P., Prodeus A.P., Filipenko M.L. Determining reference ranges for TREC and KREC assays in immune deficiency screening of newborns in Russian Federation // Medical Immunology (Russia). 2019. Vol. 21, no. 3, pp. 527–538. (In Russ.)] doi: 10.15789/1563-0625-2019-3-527-538
    6. 
																			
  6. Kondratenko I.V. Primary immunodeficiencies // Medical Immunology (Russia). 2005. Vol. 7, no. 5-6, pp. 467–476. (In Russ.)] doi: 10.15789/1563-0625-2005-5-6-467-476
    7. 
																			
  7. Tangye S.G., Al-Herz W., Bousfiha A., Cunningham-Rundles C., Franco J.L., Holland S.M., Klein C., Morio T., Oksenhendler E., Picard C., Puel A., Puck J., Seppänen M.R.J., Somech R., Su H.C., Sullivan K.E., Torgerson T.R., Meyts I. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee // Journal of Clinical Immunology. 2022. Vol. 42, no. 7, pp. 1473–1507. doi: 10.1007/s10875-022-01289-3
    8. 
																			
  8. Poli M.C., Aksentijevich I., Bousfiha A., Cunningham-Rundles C., Hambleton S., Klein C., Morio T., Picard C., Puel A., Rezaei N., Seppänen M.R.J., Somech R., Su H.C., Sullivan K.E., Torgerson T.R., Meyts I., Tangye S.G. Human Inborn Errors of Immunity: 2024 Update on the Classification from the International Union of Immunological Societies Expert Committee. International Union of Immunological Societies, 2025. 79 p. URL: https://wp-iuis.s3.eu-west-1.amazonaws.com/app/uploads/2025/01/08170257/IEI-Final-Update-of-2024-Report-Jan-2025.pdf (дата обращения: 10.02.2025)
    9. 
																			
  9. Korsunsky I.A., Kudlay D.A., Prodeus A.P., Shcherbina A.Yu., Rumyantsev A.G. Neonatal screening for primary immunodeficiency conditions and T-/B-cell lymphopenias as a basis for forming risk groups of children with congenital pathologies // Pediatriya, 2020. Vol. 99, no. 2., 8-15. (In Russ.)] doi: 10.24110/0031-403X-2020-99-2-8-15
    10. 
																			
  10. Prodeus A.P., Odinaeva N.D., Voronin S.V., Zakharova I.N., Tuzankina I.A., Volodin N.N., Zhdanov K.V., Pampura A.N., Sadykova D.I., Kondratyeva E.I., Korsunsky A.A., Degtyareva E.A., Savostyanov K.V., Trusova S.A., Lobenskaya A.Yu., Nikonova E.S., Lebedeva A.S., Loshkova E.V., Denisova V.D., Rumyantsev A.G. Guidelines for routing, monitoring and management tactics of immunocompromised children at risk and patients with congenital immune defects // Pediatria n.a. G.N. Speransky, 2024. Vol. 103, no. 6, pp. 218-245. (In Russ.)] doi: 10.24110/0031-403X-2024-103-6-218-245
    11. 
																			
  11. Voronin S.V., Zinchenko R.A., Efimova I.Yu., Kutsev S.I., Marakhonov A.V., Mukhina A.A., Novichkova G.A., Pershin D.E., Rodina Yu.A., Rumyantsev A.G., Shcherbina A.Yu. Neonatal screening, postnatal diagnosis and tactics of preclinical treatment and prevention of primary immunodeficiencies in children. // Guidelines by the experts from the National Association of Experts in Primary Immunodeficiencies (NAEPID) and the Association of Medical Genetics (AMG) of Russia // Pediatria n.a. G.N. Speransky, 2023, Vol. 102, no. 2, pp. 11-33 (In Russ.)doi: 10.24110/0031-403X-2023-102-2-11-33
    12. 
																			
  12. Saitgalina M.A., Liubimova N.E., Ostankova Yu.V., Kuznetzova R.N., Totolian A.A. Determination of reference values for TREC and KREC in circulating blood of the persons over 18 years // Medical Immunology, 2022, Vol. 24, no. 6, pp. 1227-1236 (In Russ.)doi: 10.15789/1563-0625-DOR-2587
    13. 
																			
  13. Deryabina S.S., Tuzankina I.A., Cheremokhin D.A., Shershnev V.N., Kudlay D.A., Litvinova M.Yu., Vlasova E.V. Pilot regional project of neonatal screening for primary immunodeficiencies in Sverdlovsk Oblast of Russia. From screening to prophylactic medical checkup // Pediatria n.a. G.N. Speransky. 2023. Vol. 102, no. 3, pp. 95–106. (In Russ.)doi: 10.24110/0031-403X-2023-102-3-95-106
    14. 
																			
  14. ​ISO 20395:2019 «Biotechnology — Requirements for evaluating the performance of quantification methods for nucleic acid target sequences — qPCR and dPCR», IDT
    15. 
																			
  15. ​ISO 53022.3—2008 «Clinical laboratory technologies. Requirements for quality of clinical laboratory tests.
    16. 
																			
  16. Part 3. Assessment of laboratory tests clinical significance», IDT
    17. 
																			
  17. Horn P.S., Pesce A.J. Reference intervals: an update // Clinica Chimica Acta. 2003. Vol. 334, no. 1–2, pp. 5–23. doi: 10.1016/s0009-8981(03)00133-5
    18. 
																			
  18. Linnet K. Two-stage transformations for normalization of reference distributions evaluated // Clinical Chemistry. 1987. Vol. 33, pp. 381–386. doi: 10.1093/clinchem/33.3.381
    19. 
																	

							

						

												

							

					
Supplementary files

					



Supplementary Files


Action




	1.
	JATS XML




	Download







																															
				

						

				
				
			

			                    

                   
                



			

		Copyright (c)  Lobenskaya A.
				


					Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
			

















 СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор). 
Регистрационный номер и дата принятия решения о регистрации СМИ: серия  ПИ № 77 - 11525 от 04.01.2002.






 













 




	







	
This website uses cookies
You consent to our cookies if you continue to use our website.

About Cookies