Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024, 168(3):235-242 | DOI: 10.5507/bp.2023.028

Severe congenital T-lymphocytopenia may affect the outcome of neonatal intensive care

Ivana Hulinkova1, Veronika Medova2, Andrea Soltysova2, 3, Veronika Dobsinska4, Andrej Ficek3, Peter Ciznar1
1 Department of Paediatrics, Faculty of Medicine, Comenius University and National Institute of Children's Diseases, Bratislava, Slovak Republic
2 Institute for Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences, Bratislava, Slovak Republic
3 Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic
4 Department of Paediatric Haematology and Oncology, Bone Marrow Transplantation Unit, Faculty of Medicine, Comenius University and National Institute of Children's Diseases, Bratislava, Slovak Republic

Aim: Circular DNA segments TREC (T-cell receptor excision circles) formed during T-lymphocyte maturation in the thymus, are a sensitive marker of thymic lymphocyte production in a broader manner. Quantification using qPCR is proposed as a surrogate marker of T cell malfunction in various primary and secondary conditions in a non-SCID selected risk newborn population.

Methods: We collected 207 dry blood spot samples during the years 2015-2018, from newly admitted risk newborns. TREC values calculated per 106 cells were determined and a cut-off values of 5th percentile was set. The positive control group consisted of patients (n=13) with genetically confirmed SCID.

Results: The median TREC value was 34,591.56 (18,074.08-60,228.58) for girls resp. 28,391.20 (13,835.01-51,835.93) per 106 cells for boys, P=0.046. Neonates born by C-section have been found to have higher TREC levels compared to neonates born by spontaneous delivery (P=0.018). In the group of preterm newborns (n=104), 3.8% had TREC value < 5th percentile, half of them died due to sepsis as opposed to no fatalities in preterm newborns with sepsis and TREC value > 5th percentile. In the group of term newborns (n=103) 9 children (8.7%) had TREC < 5th percentile, half of them were treated for asphyxia, with no fatal complications.

Conclusion: TREC levels calculated for the 5th percentile of a risk neonatal group is suggested as a surrogate marker for increased risk of fatal septic complication. Early recognition of these newborns within a risk scoring system using TREC levels could lead to potentially lifesaving interventions.

Keywords: TREC, SCID, immunodeficiency, newborn screening, risk neonates

Received: February 6, 2023; Revised: June 5, 2023; Accepted: June 14, 2023; Prepublished online: July 10, 2023; Published: September 12, 2024  Show citation

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Hulinkova, I., Medova, V., Soltysova, A., Dobsinska, V., Ficek, A., & Ciznar, P. (2024). Severe congenital T-lymphocytopenia may affect the outcome of neonatal intensive care. Biomedical papers, 168(3), 235-242. doi: 10.5507/bp.2023.028
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    References

    1. Rudd BD. Neonatal T cells: A reinterpretation. Annu Rev Immunol 2020;38:229-47. Go to original source... Go to PubMed...
    2. Chan K, Puck JM. Development of population-based newborn screening of severe combined immunodeficiency. J Allergy Clin Immunol 2005;115:391-8. Go to original source... Go to PubMed...
    3. Kwan A, Puck JM. History and current status of newborn screening for severe combined immunodeficiency. Semin Perinatol 2015;39:194-205. Go to original source... Go to PubMed...
    4. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998;396(6712):690-5. Go to original source... Go to PubMed...
    5. Borte S, von Döbeln U, Fasth A, Wang N, Janzi M, Winiarski J, Sack U, Pan-Hammarström Q, Borte M, Hammarström L. Neonatal screening of severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood 2012;15(119):2552-5. Go to original source... Go to PubMed...
    6. Quinn J, Orange JS, Modell V, Modell F. Case of severe combined immunodeficiency (SCID) and lymphopenia T cell newborn screening: saving lives...one at a time. Immunol. Res 2020;68(1):48-53. Go to original source... Go to PubMed...
    7. Kuo CY, Garcia-Lloret MI, Slev P, Bohnsack JF, Chen K. Profound T-cell lymphopenia associated with prenatal exposure to purine antagonists detected by neonatal TREC screening. J Allergy Clin Immunol Pract 2017;5(1):198-200. Go to original source... Go to PubMed...
    8. Basha S, Surendran N, Pichichero M. Immune responses in neonates. Expert Rev Clin Immunol 2014;10(9):1171-84. Go to original source... Go to PubMed...
    9. Medova V, Hulinkova I, Laiferova N, Urdova V, Ciznar P, Dolnikova D, Krasnanova V, Fabri O, Ficek A, Soltysova A. The importance of defining the age-specific TREC/KREC levels for detection of various inborn errors of immunity in pediatric and adult patients. Clin Immunol 2022;245:109155. Go to original source... Go to PubMed...
    10. Puck JM. A case of newborn screening for severe combined immunodeficiency and related disorders. Ann N Y Acad Sci 2011;1246:108-17. Go to original source... Go to PubMed...
    11. Agarwal R, Deorari A. AIIMS Protocols in Neonatology, 1st Ed. India: CBS Publishers; 2015.
    12. de Felipe B, Olbrich P, Lucenas JM, Delgado-Pecellin C, Pavon-Delgado A, Marquez J, Salamanca C, Soler-Palacin P, Gonzalez-Granado LI, Antolin LF, Borte S, Neth O. Prospective newborn screening for Severe T- and B-lymphocyte deficiency in Seville. Pediatr Allergy Immunol 2016;27(1):70-7. Go to original source... Go to PubMed...
    13. Shakerian L, Pourpak Z, Shamlou S, Domsgen E, Kazemnejad A, Dalili H, Nourizadeh M. Determining Laboratory Reference Values of TREC and KREC in Different Age Groups of Iranian Healthy Individuals. Iran J Allergy Asthma Immunol 2019;18(2):143-52. Go to original source...
    14. Schlinzig T, Johansson S, Stephansson O, Hammarström L, Zetterström RH, von Döbeln U, Cnattingius S, Norman M. The rise in immune cell formation at birth varies by mode of delivery and infant characteristics - a population-based cohort study. PLoS One 2017;12(9):e0184748. Go to original source... Go to PubMed...
    15. Lisse IM, Aaby P, Whittle H, Jensen H, Engelmann M, Christensen LB. T-lymphocyte subsets in West African children: influence of age, sex, and season. J Pediatrics 1997;130(1):77-85. Go to original source... Go to PubMed...
    16. Sempowski GD, Gooding ME, Liao HX, Le PT, Haynes BF. T cell receptor excision circle assessment of thymopoiesis in aging mice. Mol Immunol 2002;38(11):841-8. Go to original source... Go to PubMed...
    17. Sharma AA, Jen R, Butler A, Lavoie PM. The developing human preterm neonatal immune system: rationale for further research in this area. Clinical immunology 2012;145(1):61-8. Go to original source... Go to PubMed...
    18. Vogel BH, Bonagura V, Weinberg GA, Ballow M, Isabelle J, DiAntonio L, Parker A, Young A, Cunningham-Rundles C, Fong CT, Celestin J, Lehman H, Rubinstein A, Siegel S, Weiner L, Saavedra-Matiz C, Kay DM, Caggana M. Newborn screening for SCID in New York State: experience from the first two years. J Clin Immunol 2014;34(3):289-303. Go to original source... Go to PubMed...
    19. Gitau R, Menson E, Pickles V, Fisk NM, Glover V, MacLachlan N. Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery. Eur J Obstet Gynecol Reprod Biol 2001;98(1):14-17. Go to original source... Go to PubMed...
    20. Prieto-Hinojosa A, Knight A, Compton C, Gleeson M, Travers PJ. Reduced thymus output in elite athletes. Brain Behav Immun 2014;39:75-9. Go to original source... Go to PubMed...
    21. Koenig JM, Stegner JJ, Schmeck AC, Saxonhouse MA, Kenigsberg LE. Neonatal neutrophils with prolonged survival show an increased inflammatory and cytotoxic response. Pediatric Res 2005;57(3):424-9. Go to original source... Go to PubMed...
    22. Yektaei-Karin E, Moshfegh A, Lundahl J, Berggren V, Hansson LO, Marchini G. Birth stress increases in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn. Children's allergy and immunology 2007;18(8):643-51. Go to original source... Go to PubMed...
    23. Gul KA, Strand J, Pettersen RD, Brun H, Abrahamsen TG. T-cell Receptor Excision Circles in Newborns with Heart Defects. Pediatr Cardiol 2020;41(4):809-15. Go to original source... Go to PubMed...
    24. Paw³owski B, Nowak J, Borkowska B, Augustyniak D, Drulis-Kawa Z. Body height and immune efficacy: testing body stature as a signal of biological quality. Proc Biol Sci 2017;284(1859):20171372. Go to original source... Go to PubMed...
    25. Olbrich P, de Felipe B, Delgado-Pecellin C, Rodero R, Rojas P, Aguayo J, Marquez J, Casanovas J, Sánchez B, Lucena JM, Ybot-Gonzalez P, Borte S, Neth O. A first pilot study on the neonatal screening of primary immunodeficiencies in Spain: TRECS and KRECS identify severe T- and B-cell lymphopenia. An Pediatr (Barc) 2014;81(5):310-17. Go to original source... Go to PubMed...
    26. Ye P, Kirschner DE. Measuring emigration of human thymocytes by T-cell receptor excision circles. Crit Rev Immunol 2002;22(5-6):483-97. Go to original source...
    27. Raqib R, Alam DS, Sarker P, Ahmad SM, Ara G, Yunus M, Moore SE, Fuchs G. Low birth weight is associated with altered immune function in children in rural Bangladesh: a birth cohort study. Am J Clin Nutr 2007;85(3):845-52. Go to original source... Go to PubMed...
    28. Castagnoli R, Delmonte OM, Calzoni E, Notarangelo LD. Hematopoietic Stem Cell Transplantation in Primary Immunodeficiency Diseases: Current Status and Future Perspectives. Front Pediatr 2019;7:295. Go to original source... Go to PubMed...
    29. Gaspar HB, Cooray S, Gilmour KC, Parsley KL, Adams S, Howe SJ, Al Ghonaium A, Bayford J, Brown L, Davies EG, Kinnon C, Thrasher AJ. Long-term persistence of the polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med 2011;3(97):97ra79. doi: 10.1126/scitranslmed.3002715 Go to original source... Go to PubMed...
    30. Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, Veys P, Gennery AR, Gaspar HB. Neonatal diagnosis of severe combined immunodeficiency results in significantly improved survival outcome: the case for newborn screening. Blood 2011;117(11):3243-6. Go to original source... Go to PubMed...
    31. Amatuni GS, Sciortino S, Currier RJ, Naides SJ, Church JA, Puck JM. Reference intervals for lymphocyte subsets in premature and full-term neonates without immune defects. J. Allergy Clin Immunol 2019;144(6):1674-83. Go to original source... Go to PubMed...
    32. van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC-based neonatal screening for severe combined immunodeficiency: a systematic review. J Clin Immunol 2015;35(4):416-30. Go to original source... Go to PubMed...
    33. Adams SP, Rashid S, Premachandra T, Harvey K, Ifederu A, Wilson MC, Gaspar HB. Screening for neonatal dry blood spots in the United Kingdom using the TREC duplex screening test. J Clin Immunol 2014;34(3):323-30. Go to original source... Go to PubMed...

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