Newborn screening for severe combine immunodeficiency: first year results in Krasnodar region

Aim. Assessment of the results of the first year of neonatal screening for SCID in Krasnodar region and identification of factors affecting the level of analyzed indicators

Methods. During the first year, 47073 infants were screened for SCID in Krasnodar region, using real-time PCR to quantitate T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circle (KREC). The average levels of TREC and KREC in children of different gestational ages were calculated, and relationships between these indicators were identified using the Kruskal-Wallis test.

Results. According to the results of the study, 4 groups of children of different gestational age were analyzed, according to the WHO classification: the most significant associative relationship between the amount of TREC and KREC in the blood of a child with gestation period was revealed. During the period of the screening 102 newborns of the PIDS-risk group, 93 samples were delivered to the Medical and Genetic Research Center, Moscow. Confirmation of reduced TREC/KREC levels was received for 17 children. At the same time, primary immunodeficiency, as the main diagnosis, has not been established in any patient. Two children with chromosomal pathology were diagnosed with PIDS as a concomitant diagnosis. Two children are on the dispensary register with an immunologist due to deviations in the results of immunophenotyping but with a normal amount of TREC / KREC after retest.

Conclusion. The results obtained demonstrate that neonatal screening for PIDs using real-time PCR is an effective element of clinical practice, allowing timely detection of hereditary diseases, which, in turn, accelerates the prescription of pathogenetic therapy, reducing the level of disability and mortality among newborns. 

1. Khalturina E.O., Degtyareva N.D., Bairashevskaia A.V. et al. Modern diagnostic capabilities of neonatal screening for primary immunodeficiencies in newborns. Clin Exp Pediatr. 2021;63: 504-10.

2. Filipenko М.L., Rumyantsev A.G, Prodeus A.P., et al. Skrining novorozhdennykh na pervichnyye immunodefitsity i gruppu riska immunoregulyatornykh rasstroystv, trebuyushchikh dispansernogo nablyudeniya [Screening of newborns for primary immunodeficiencies and risk groups for immunoregulatory disorders requiring follow up]. Pediatriya im. G.N. Speranskogo [Pediatria n.a. G.N. Speransky]. 2019; 98 (3): 49-54. (In Russ.)

3. Tuzankina I.A., Deryabina S.S., Bolkov M.A. Pervichnyye immunodefitsity v rannem vozraste [Primary immunodeficiencies at an early age]. M. 2018;176 p. (In Russ.)

4. Yao C., Han X., Zhang Y. et al. Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004–2011). J Clin Immunol. 2013;33:526–39

5. Bousfiha A., Moundir A., Tangye S.G., et al. The 2022 Update of IUIS Phenotypical Classification for Human Inborn Errors of Immunity. J Clin Immunol. 2022;42(7):1508-1520. doi: 10.1007/s10875-022-01352-z.

6. Chernyishova E.V., Anastasevich L.A., Scherbina А.Y., Larin S.S. Sovremennyye vozmozhnosti skrininga i diagnostiki pervichnykh immunodefitsitnykh sostoyaniy v pediatrii [Modern possibilities of screening and diagnosis of primary immunodeficiency in pediatrics]. Pediatriya im. G.N. Speranskogo [Pediatria n.a. G.N. Speransky]. 2016; 95 (3).. 2016;3:124-128. (In Russ.)

7. Currier R., Puck J.M. SCID newborn screening: What we’ve learned. J Allergy Clin Immunol. 2021; 147(2): 417–426.

8. Baker M.W., Grossman W.J., Laessig R.H. et al. Development of a routine newborn screening protocol for severe combined immunodeficiency. J Allergy Clin Immunol. 2009;124:522-527.

9. Rechavi E., Lev A., Simon A.J. et al. First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency. Clinical Achievements and Insights. Front Immunol. 2017;8:1448.

10. Tesorero R., Janda J., Horster F. et al. A high-throughput newborn screening approach for SCID, SMA, and SCD combining multiplex qPCR and tandem mass spectrometry. PLoS ONE 18(3): e0283024

11. Nourizadeh M., Shakerian L., Borte S. et al. Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran. Scand J Immunol. 2018; 88:e12699

12. Kwan A. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014; 312 (7): 729–738.

13. Modell V., Knaus M., Modell F. et al. Global overview of primary immunodeficiencies: a report from Jeffrey Modell Centers worldwide focused on diagnosis, treatment, and discovery. Immunol. Res. 2014; 60 (1): 132–144

14. Puck J.M. Population-based newborn screening for severe combined immunodeficiency: Steps toward implementation. J. Allergy Clin. Immunol. 2007; 120: 760–768.

15. Marakhonov A.V., Efimova I.Y., Mukhina A.A. et al. Newborn Screening for Severe T and B Cell Lymphopenia Using TREC/KREC Detection: A Large-Scale Pilot Study of 202,908 Newborns. J Clin Immunol. 2024; 44: 93.

16. Neonatal’nyy skrining:natsional’noye rukovodstvo / pod red.S.I.Kutseva.– Moskva: GEOTAR-Media [Neonatal screening: national guidelines / edited by S.I. Kutsev. – Moscow: GEOTAR-Media], 2023.– 360p. (In Russ.)

17. Classification of premature birth. Available at: https://www.who.int/ru/news-room/fact-sheets/detail/preterm-birth.

18. Moens L.N., Falk-Sörqvist E., Asplund A.C. et al. Diagnostics of primary immunodeficiency diseases: a sequencing capture approach. PLoS One. 2014. 11;9(12):e114901.

19. Barbaro M., Ohlsson A., Borte S. et al. Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden − a 2-Year Pilot TREC and KREC Screening Study. J Clin Immunol. 2017; 37:51–60

20. Deryabina S.S. Rol’ kolichestvennogo opredeleniya kol’tsevykh uchastkov DNK T-kletochnogo i V-kletochnogo retseptorov limfotsitov v otsenke funktsionirovaniya immunnoy sistemy novorozhdennykh i detey pervogo goda zhizni. Dis. kandidata meditsinskikh nauk [The role of quantitative determination of circular DNA sections of T-cell and B-cell receptors of lymphocytes in assessing the functioning of the immune system of newborns and children of the first year of life. Dis. candidate of medical sciences]. Ekaterinburg. 2017;177p. (In Russ.)

21. Cheremokhin D.A., Shinwari K., Deryabina S.S., Bolkov M.A., Tuzankina I.A., Kudlay D.A. Analiz urovney TRES i KREC v obraztsakh sukhoy krovi novorozhdennykh raznogo gestatsionnogo vozrasta i vesa [Analysis of the TREC and KREC Levels in the Dried Blood Spots of Healthy Newborns with Different Gestational Ages and Weights]. Acta Naturae (russkoyazychnaya versiya) [Acta Naturae]. 2022; 14(1):101-108. doi: 10.32607/actanaturae.11501. (In Russ.)

22. Deryabina S.S., Tuzankina I.A., Shershnev V.N. Opredeleniye normativnykh znacheniy TREC i KREC v sukhikh pyatnakh krovi novorozhdennykh raznogo sroka gestatsii v Sverdlovskoy oblasti [Determination of reference values for TREC and KREC in dry blood spots of newborns from different gestation ages in Sverdlovsk region]. Meditsinskaya immunologiya [Medical Immunology (Russia)]. 2018;20(1):85-98. (In Russ.) https://doi.org/10.15789/1563-0625-2018-1-85-98