Dynamics of T-receptor and kappa-deletion recombination excision ring levels as indicators of immune system integrity in newborns of different gestational ages: influence of maternal factors

• Elena N. Volkova
• Lyudmila I. Ippolitova

Abstract

The sufficient number of studies on the dynamics of TREC (T-cell receptor excision circle) and KREC (kappa-deleting recombination excision circle) levels in both preterm infants and older children. The data are limited and contradictory for preterm babies. Therefore, is required further research to better understand the dynamics of markers in the research group.

Objective. Assessment of the dynamics of TREC and KREC levels in newborns with different gestational ages. Study significant maternal risk factors affecting the interested criteria.

Material and methods. The cross-sectional (simultaneous) study included 203 newborns with a gestation period of 22–41 weeks, born in 2023–2024. The dynamics of TREC and KREC were evaluated. The influence of maternal factors on TREC and KREC indicators was considered. The material for the study – dried blood stains drawn on Guthrie cards and taken as part of neonatal screening.

Results. A gradual increase in the levels of KREC and TREC due to gestational age was evaluated. Mostly intensive, the process takes part in a 28–30 week group of patients. Afterward, the interesting for us values reach a plateau. It was found that there was a statistically significant decrease in TREC levels in newborns from women with a history of spontaneous miscarriages (p=0.002); medical abortions (p=0.021) and congenital kidney malformations (p=0.01). The level of CREC was statistically significantly decreased in the group of newborns with a mother’s history of chronic salpingitis and oophoritis (p=0.03), chronic pyelonephritis (p=0.031)

Conclusion. The strong correlation between KREC/TREC levels and gestational age was noted. Statistically significant maternal factors influencing the assessed parameters have been identified. The question remains open as to the degree of their influence on TREC and KREC values.

Keywords: inborn error of immunity; T-cell receptor excision circle; kappa-deleting recombination excision circle; prematurity

References

1. Khadzhieva М.В., Kalinina Е.V., Larin S.S., et al. TREC/KREC levels in young COVID-19 patients. Diagnostics (Basel). 2021; 11 (8): 1489.

2. Cheremokhin D.A., Shinvari X., Deryabina S.S., et al. Analysis of TREK and KREC levels in dry blood samples of newborns of different gestational age and weight. Acta Naturae (Russian version). 2022; (14): 101–8. (in Russian)

3. Boyarchuk O., Yarema N., Kravets V., et al. Newborn screening for severe combined immunodeficiency: the results of the first pilot TREC and KREC study in Ukraine with involving of 10,350 neonates. Front Immunol. 2022; 13: 1–13.

4. Kwok J., Cheung S., Y Ho J., et al. Establishing simultaneous T Cell Receptor Excision Circles (TREC) and K-Deleting Recombination Excision Circles (KREC) quantification assays and laboratory reference intervals in healthy individuals of different age groups in Hong Kong. Front Immunol. 2020; 11: 1411.

5. Şentürk G., Ng Y.Y., Eltan S.B., et al. Determining T and B Cell development by TREC/KREC analysis in primary immunodeficiency patients and healthy controls. Scand J Immunol. 2021; 95 (7): e13130.

6. Trück J., Prader S., Natalucci G., et al. Swiss newborn screening for severe T and B cell deficiency with a combined TREC/KREC assay – management recommendations. Swiss Med Wkly. 2020; 150: w20254.

7. Gizewska, M., Durda K., Winter T., et al. Newborn screening for SCID and other severe primary immunodeficiency in the Polish-German transborder area: experience from the first 14 months of collaboration. Front Immunol. 2020; 11: 1948.

8. 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.

9. De Felipe B., Olbrich P., Lucenas J., et al. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville. Pediatr Allergy Immunol. 2016; 27 (1): 70–7.

10. Remaschi G., Ricci S., Cortimiglia M., et al. TREC and KREC in very preterm infants: reference values and effects of maternal and neonatal factors. J Matern Fetal Neonatal Med. 2019; 34 (23): 1–6.

11. Kanegae M., Barreiros L., Sousa J., et al. Newborn screening for severe combined immunodeficiencies using TRECS and KRECS: second pilot study in Brazil. Rev Paul Pediatr. 2017; 35 (1): 25–32.

12. O’Connell A. Primary immunodeficiency in the NICU. Neoreviews. 2019; 20 (2): e67–78.

13. Mongkonsritragoon W., Huang J., Fredrickson M., et al. Positive newborn screening for severe combined immunodeficiency: what should the pediatrician do? Clin Med Insights Pediatr. 2023; 17: 1–9.

14. Prodeus A.P., Marakhonov A.V. Diagnosis of immunodeficiency conditions in children: clinical and laboratory aspects. In: Proceedings of the Scientific-Practical Conference «Orphanetics: All-Russian Multidisciplinary Conference with International Participation». Moscow, 2024. (in Russian)

15. Zhang J., Quintal L., Atkinson A., et al. Novel RAG1 mutation in a case of severe combined immunodeficiency. Pediatrics. 2015; 116 (3): 445–9.

16. Holt P.G., Jones C.A. The development of the immune system during pregnancy and early life. Allergy. 2000; 55 (8): 688–97.

17. Tuzankina I.A. Primary immunodeficiency (innate errors of immunity) at an early age. Tashkent: Adast-poligraf, 2022: 232 р. (in Russian)

18. Vermijlen D., Prinz I. Ontogeny of innate T lymphocytes – some innate lymphocytes are more innate than others. Front Immunol. 2014; 10 (5): 486.

19. Rechavi E., Lev A., Simon A., et al. First year of Israeli newborn screening for severe combined immunodeficiency – clinical achievements and insights. Front Immunol. 2017; 8 (1): 1448.

20. Moro-Garcia M.A., Alonso-Arias R., Lopez-Larrea C. Molecular mechanisms involved in the aging of the T-cell immune response. Curr Genomics. 2012; 13 (8): 589–602.

21. Ye P., Kirschner D. Measuring emigration of human thymocytes by T-cell receptor excision circles. Crit Rev Immunol. 2022; 22 (5): 483–97.

22. Olbrich P., de Felipe B., Delgado-Pecellin C., et al. A first pilot study on the neonatal screening of primary immunodeficiencies in Spain: TRECS and KRECS identify severe T- and B- cell limphopaenia. Ann Pediatr (Barc). 2014; 81 (5): 310–7.

23. Levchenko L., Il’ina A., Cherkasova S. Congenital pneumonia in newborns (literature review). Mediko-sotsial’nye problemy sem’i [Medical and Social Problems of the Family]. 2022; 27 (2): 130–5. (in Russian)

24. Shadeeva Yu., Gur’eva V. Risk factors for intrauterine infection in early and early preterm labor complicated by rupture of amniotic membranes. Mat’ i ditya v Kuzbasse [Mother and Child in Kuzbass]. 2019; 4 (79): 33–9. (in Russian)

25. Mayden I., Spivak E. Features of the functional state of lymphocytes in premature newborns. Permskiy meditsinskiy zhurnal [Perm Medical Journal]. 2019; 36 (6): 27–32. (in Russian)

26. Feleke B.E., Feleke T.E. A longitudinal study on the effects of previous stillbirth or abortion on subsequent pregnancies and infants. Eur J Public Health. 2021; 6: 1–5.

27. Kashatnikova D.A., Khadzhieva M.B., Kolobkov D.S., et al. Pneumonia and related conditions in critically ill patients – insights from basic and experimental studies. Int J Mol Sci. 2022; 23 (17): 9896.

28. Boato R., Aguiar M., Mak R., et al. Maternal risk factors for congenital anomalies of the kidney and urinary tract: a case-control study. J Pediatr Urol. 2023; 19 (2): e1–11.

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