Original Article
 

Determining Laboratory Reference Values of TREC and KREC in Different Age Groups of Iranian Healthy Individuals

Abstract

Assessment of the number of T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) copies has been recently described as biomarkers of newly formed T and B cells respectively. In this study, we aimed to explore the effects of demographic variables including age, gender, weight, height and ethnicity on these two episomal DNA molecules. Second, for the first time in our country, we determined the reference values of TREC and KREC copy numbers in different age groups of Iranian healthy individuals as a threshold for identifying T cell and B cell lymphopenia. The TREC and KREC copy numbers were evaluated in 251 dried blood spot (DBS) samples from healthy volunteers (age range: 0-60 years). Six primary immunodeficiency (PID) patients were included as disease controls. TREC and KREC copies were markedly reduced with increasing age. Although the levels of TREC and KREC were higher in females than males, this difference did not reach statistical significance. These findings suggest that demographic variables including age should be considered for interpretation results of the TREC/KREC assay.

1. Ye P, Kirschner DE. Measuring emigration of human thymocytes by T-cell receptor excision circles. Critical reviews in immunology. 2002;22(5-6):483-97.


2. Barbaro M, Ohlsson A, Borte S, Jonsson S, Zetterstrom RH, King J, et al. Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year Pilot TREC and KREC Screening Study. Journal of clinical immunology. 2017;37(1):51-60.


3. Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. The Journal of allergy and clinical immunology. 2005;115(2):391-8.


4. Shrivastava A, Gupta A, Gupta A, Shrivastava J. Unusual presentation of intussusception of the small bowel with peutz jeghers syndrome: report of a case. Journal of clinical and diagnostic research : JCDR. 2013;7(10):2296-7.


5. Quiros-Roldan E, Serana F, Chiarini M, Zanotti C, Sottini A, Gotti D, et al. Effects of combined antiretroviral therapy on B- and T-cell release from production sites in long-term treated HIV-1+ patients. Journal of translational medicine. 2012;10:94.


6. de Felipe B, Olbrich P, Lucenas JM, Delgado-Pecellin C, Pavon-Delgado A, Marquez J, et al. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2016;27(1):70-7.


7. Van Zelm M, Van Der Burg M, Langerak A, Van Dongen J. PID Comes Full Circle: Applications of V(D)J Recombination Excision Circles in Research, Diagnostics and Newborn Screening of Primary Immunodeficiency Disorders. Frontiers in Immunology. 2011;2(12).


8. Borte S, von Dobeln U, Fasth A, Wang N, Janzi M, Winiarski J, et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012;119(11):2552-5.


9. Claustres M, Kozich V, Dequeker E, Fowler B, Hehir-Kwa JY, Miller K, et al. Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic). European journal of human genetics : EJHG. 2014;22(2):160-70.


10. Filali-Ansary A, Auge C, Abgrall A, Souchaud M, Pellissier F, Mordt OV, et al. A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and its active metabolites. Bioanalysis. 2016;8(19):2045-63.


11. Sottini A, Serana F, Bertoli D, Chiarini M, Valotti M, Vaglio Tessitore M, et al. Simultaneous quantification of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) by real-time PCR. Journal of visualized experiments : JoVE. 2014(94).


12. Lamyaa Salem HAT, Salwa Bakr, Afaf A. Mostafa, Nesrine A Mohamed. Simultaneous Quantification of T-Cell Receptor Excision Circles (TRECs) and K-Deleting Recombination Excision Circles (KRECs) by Real-time PCR. International Journal of Advanced Research. 2016;4(4): 1251-8.


13. M.A H. Stem cells and canser stem cells 4 therapeutic applications in diseases and injury.


14. Yoshida K, Nakashima E, Kubo Y, Yamaoka M, Kajimura J, Kyoizumi S, et al. Inverse associations between obesity indicators and thymic T-cell production levels in aging atomic-bomb survivors. PloS one. 2014;9(3):e91985.


15. Klein SL, Flanagan KL. Sex differences in immune responses. Nature reviews Immunology. 2016;16(10):626-38.


16. Chao TC. Female sex hormones and the immune system. Changgeng yi xue za zhi. 1996;19(1):95-106.


17. Giefing-Kroll C, Berger P, Lepperdinger G, Grubeck-Loebenstein B. How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging cell. 2015;14(3):309-21.


18. van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. Journal of clinical immunology. 2015;35(4):416-30.


19. Puck JM. The case for newborn screening for severe combined immunodeficiency and related disorders. Annals of the New York Academy of Sciences. 2011;1246:108-17.


20. Jilkina O, Thompson JR, Kwan L, Van Caeseele P, Rockman-Greenberg C, Schroeder ML. Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and other primary immunodeficiency diseases. Molecular genetics and metabolism reports. 2014;1:324-33.


21. Raqib R, Alam DS, Sarker P, Ahmad SM, Ara G, Yunus M, et al. Low birth weight is associated with altered immune function in rural Bangladeshi children: a birth cohort study. The American journal of clinical nutrition. 2007;85(3):845-52.


22. Castermans E, Morrhaye G, Marchand S, Martens H, Moutschen M, Geenen V, et al. [Evaluation of thymopoiesis: clinical applications]. Revue medicale de Liege. 2007;62(12):725-9.


23. Geenen V, Poulin JF, Dion ML, Martens H, Castermans E, Hansenne I, et al. Quantification of T cell receptor rearrangement excision circles to estimate thymic function: an important new tool for endocrine-immune physiology. The Journal of endocrinology. 2003;176(3):305-11.


24. Sempowski GD, Gooding ME, Liao HX, Le PT, Haynes BF. T cell receptor excision circle assessment of thymopoiesis in aging mice. Molecular immunology. 2002;38(11):841-8.


25. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396(6712):690-5.


26. Serana F, Airo P, Chiarini M, Zanotti C, Scarsi M, Frassi M, et al. Thymic and bone marrow output in patients with common variable immunodeficiency. Journal of clinical immunology. 2011;31(4):540-9.


27. Moro-Garcia MA, Alonso-Arias R, Lopez-Larrea C. Molecular mechanisms involved in the aging of the T-cell immune response. Current genomics. 2012;13(8):589-602.


28. Serana F, Chiarini M, Zanotti C, Sottini A, Bertoli D, Bosio A, et al. Use of V(D)J recombination excision circles to identify T- and B-cell defects and to monitor the treatment in primary and acquired immunodeficiencies. Journal of translational medicine. 2013;11:119.


29. Chen X, Barfield R, Benaim E, Leung W, Knowles J, Lawrence D, et al. Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients. Blood. 2005;105(2):886-93.


30. Puck JM. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles. The Journal of allergy and clinical immunology. 2012;129(3):607-16.

Files
IssueVol 18, No 2 (2019) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v18i2.917
Keywords
Immunodeficiency Kappa-deleting recombination excision circles Reference value T-cell receptor excision circles

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
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):143-152.