ASSESSMENT OF THE NUMBER OF T-CELL RECEPTOR EXCISION CIRCLE (TREC) AND KAPPA-DELETING RECOMBINATION EXCISION CIRCLE (KREC) IN CHILDREN WITH CONGENITAL HEART DEFECTS AND WITH FORCED THYMECTOMY
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Abstract
The aim of this study was to evaluate the levels of TREC and KREC in children of the first year of life with congenital heart defects (CHD) and forced thymectomy.
Copies of TREC, KREC and the IL17RA gene were quantified in isolated DNA from 100 µl of whole blood of 28 infants with congenital heart disease, represented by defects in the interventricular and interatrial septa, as well as their combinations with each other and with defects in the valves and blood vessels of the heart. The forced thymectomy was performed in 14 children (age 0.4 ± 0.2 years), the thymus was preserved (operation from a mini-access or by endovascular intervention) in 14 patients (age 1.1 ± 0.3 years).
The study showed a positive correlation between the age of children and the level of TREC in peripheral blood, and a negative relationship between age and KREC levels. In children with congenital heart disease and forced thymectomy, the amount of TREC was significantly lower than in children with preserved thymus and conditionally healthy newborns. The number of KRECs in children with CHD and forced thymectomy was significantly higher than in children without it.
Carrying out forced thymectomy in children of the first year of life in the surgical treatment of CHD is a risk factor for the formation of immunodeficiency states in them.
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1. https://eu-rd-platform.jrc.ec.europa.eu/eurocat/eurocatdata/prevalence_en.
2. Borisenko DV, Ivkin AA, Shukevich DL. Modern methods of limiting the systemic inflammatory response in the correction of congenital heart defects in children under cardiopulmonary bypass. Complex problems of cardiovascular diseases. 2021; 10(2): 113-124. Russian. (Борисенко Д.В., Ивкин А.А., Шукевич Д.Л. Современные методы ограничения системного воспалительного ответа при коррекции врожденных пороков сердца у детей в условиях искусственного кровообращения // Комплексные проблемы сердечно-сосудистых заболеваний. 2021. Т.10, № 2. С. 113-124. doi:10.17802/2306-1278-2021-10-2-113-124.)
3. Chiarini M, Zanotti C, Serana F, Sottini A, Bertoli D, Caimi L, Imberti L. T-cell receptor and K-deleting recombination excision circles in newborn screening of T- and B-cell defects: review of the literature and future challenges. Journal of Public Health Research. 2013; 2(1): 9-16.
4. Bousfiha AA, Jeddane L, Ailal F, Benhsaien I, Mahlaoui N, Casanova JL, Abel L. Primary immunodeficiency diseases worldwide: more common than generally thought. J Clin Immunol. 2013;33(1):1-7. doi: 10.1007/s10875-012-9751-7.
5. Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009;84(1):16-22. doi: 10.4065/84.1.16.
6. Diller GP, Lammers AE, Fischer A, Orwat S, Nienhaus K, Schmidt R, Radke RM, De-Torres-Alba F, Kaleschke G, Marschall U, Bauer UM, Roth J, Gerß J, Bormann E, Baumgartner H. Immunodeficiency is prevalent in congenital heart disease and associated with increased risk of emergency admissions and death. Eur Heart J. 2023 Sep 7;44(34):3250-3260. doi: 10.1093/eurheartj/ehad029.
7. Deryabina SS, Tuzankina IA, Shershnev VN. Determination of reference values for trec and krec in dry blood spots of newborns from different gestation ages in sverdlovsk region. Medical Immunology (Russia). 2018;20(1):85-98. Russian (Дерябина С.С., Тузанкина И.А., Шершнев В.Н. Определение нормативных значений TREC и KREC в сухих пятнах крови новорожденных разного срока гестации в Свердловской области // Медицинская иммунология. 2018. Т. 20, № 1. С. 85-98. doi: 10.15789/1563-0625-2018-1-85-98.)
8. Gordukova MA, Oskorbin IP, Mishukova OV, Zimin SB, Zinovieva NV, Davydova NV, Smirnova AS, Nikitina IA, Korsunsky IA, Filipenko ML, Prodeus AP. Development of real-time multiplex pcr for the quantitative determination of trec's and krec's in whole blood and in dried blood spots. Medical Immunology (Russia). 2015;17(5):467-478. Russian (Гордукова М.А., Оскорбин И.П., Мишукова О.В., Зимин С.Б., Зиновьева Н.В., Давыдова Н.В., Смирнова А.С., Никитина И.А., Корсунский И.А., Филипенко М.Л., Продеус А.П. Разработка набора реагентов для количественного определения молекул ДНК TREC и KREC в цельной крови и сухих пятнах крови методом мультиплексной ПЦР в режиме реального времени // Медицинская иммунология, 2015. Т. 17, № 5. С. 467-478.)
9. Deryabina SS, Tuzankina IA, Vlasova EV, Shershnev VN. Quantitative assessment of TREC and KREC for children with impaired function of their immune system in the first year of life. Medical Genetics, 2015;2: 53-54. Russian (Дерябина С.С., Тузанкина И.А., Власова Е.В., Шершнев В.Н. Количественная оценка кольцевых структур TREC и KREC у детей с нарушениями функции иммунной системы на первом году жизни // Меди-цинская генетика, 2015. № 2. С. 53-54.).
10. Revyakina VA, Astafieva NG, Geppe NA, Kalyuzhin OV. Updated PRIMA Conciliation Document to Help the Practitioner. Pediatrics. Consilium Medicum. 2021; 2:109–112. DOI: 10.26442/26586630.2021.2.200992. Russian (Ревякина В.А., Астафьева Н.Г., Геппе Н.А., Калюжин О.В. Обновленный согласительный документ ПРИМА в помощь практическому врачу. Педиатрия. Consilium Medicum. 2021; 2: 109–112.).
11. Goldmuntz E. 22q11.2 deletion syndrome and congenital heart disease. Am J Med Genet C Semin Med Genet. 2020;184(1):64-72. doi: 10.1002/ajmg.c.31774.
12. Rovda Y I, Shmulevich SA, Shabaldin AV, Shabaldina EV, Minyaylova NN, SizovaIN, Lukoyanycheva EB. Clinical and immunological characteristics of children in a catamnesis after surgery for congenital heart diseases, combined with induced thymectomy. Pediatria. 2018; 97(4): 50-58. Russian (Ровда Ю.И., Шмулевич С.А., Шабалдин А.В., Шабалдина Е.В., Миняйлова Н.Н., Сизова И.Н., Лукоянычева Е.Б. Клинико-иммунологические характеристики детей в катамнезе, после операции по поводу врожденного порока сердца, сочетанной с вынужденной тимусэктомией // Педиатрия. 2018. Т. 97, № 4. С. 50-58)
13. Rovda YI, Shmulevich SA, Shabaldin AV, Lukoyanycheva EB. Subpopulation profiles of T helper cells expressing CD45RA and CD31 markers in children after thymectomy performed upon surgical treatment of congenital heart disease. Meditsinskaya immunologiya, 2016; 18(2): 119. Russian (Ровда Ю.И., Шмулевич С.А., Шабалдин А.В., Лукоянычева Е.Б. Особенности субпопуляций т-лимфоцитов хелперов, экспрессирующих cd45ra- и cd31- маркеры, у детей после тимэктомии, выполненной при хирургическом лечении врожденного порока сердца // Медицинская иммунология. 2016. Т18, №2. С.119-128.)
14. Madhok AB, Chandrasekran A, Parnell V, Gandhi M, Chowdhury D, Pahwa S. Levels of recent thymic emigrant cells decrease in children undergoing partial thymectomy during cardiac surgery. Clin Diagn Lab Immunol. 2005;12(5):563-5. doi: 10.1128/CDLI.12.5.563-565.2005.
15. Mancebo E, Clemente J, Sanchez J, Ruiz-Contreras J, De Pablos P, Cortezon S, Romo E, Paz-Artal E, Allende LM. Longitudinal analysis of immune function in the first 3 years of life in thymectomized neonates during cardiac surgery. Clin Exp Immunol. 2008;154(3):375-83. doi: 10.1111/j.1365-2249.2008.03771.x.
16. Cavalcanti NV, Palmeira P, Jatene MB, de Barros Dorna M, Carneiro-Sampaio M. Early Thymectomy Is Associated With Long-Term Impairment of the Immune System: A Systematic Review. Front Immunol. 2021;12:774780. doi: 10.3389/fimmu.2021.774780.
17. Gudmundsdottir J, Óskarsdóttir S, Skogberg G, Lindgren S, Lundberg V, Berglund M, Lundell AC, Berggren H, Fasth A, Telemo E, Ekwall O. Early thymectomy leads to premature immunologic ageing: An 18-year follow-up. J Allergy Clin Immunol. 2016;138(5):1439-1443.e10. doi: 10.1016/j.jaci.2016.05.014.
18. Yarilin AA, Donetskova AD. T-cells: recent thymic emigrants. Immunology. 2012; 6:326–334 (Ярилин А.А., Донецкова А.Д. Т–клетки недавние эмигранты из тимуса // Иммунология. 2012, Т 6. С. 326–334).
19. Donetskova AD, Frolenko AL, Troshina VV, Smolyagin AI, Yarilin AA. Thymus excision rings in peripheral blood lymphocytes. Age dynamics and influence of thymectomy. Immunology. 2010; 6: 293-299. Russian (ДонецковаА.Д., ФроленкоА.Л., ТрошинаВ.В., СмолягинА.И., ЯрилинА.А. Тимусныеэксцизионные кольца в лимфоцитах периферической крови. Возрастная динамика и влияние тимэктомии //Иммунология. 2010. № 6. С. 293-299.);
20. Kimmig S, Przybylski GK, Schmidt CA, Laurisch K, Möwes B, Radbruch A, Thiel A. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J Exp Med. 2002; 195(6):789-794.
21. angye SG, Al-Herz W, Bousfiha A, Chatila T, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Picard C, Puck J, Torgerson TR, Casanova JL, Sullivan KE. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2020;40(1):24-64. doi: 10.1007/s10875-019-00737-x. Erratum in: J Clin Immunol. 2020;40(1):65. doi: 10.1007/s10875-020-00763-0.
22. Федеральные клинические рекомендации по диагностике и лечению детей с тяжелой комбинированной иммунной недостаточностью. РАЗРАБОТАН: Общественная организация Национальное общество детских гематологов, онкологов; ФГБУ «ФНКЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Румянцев А.Г., Масчан А.А., Щербина А.Ю. Издание официальное. Москва. 2015. 28 с. [Federal clinical guidelines for the diagnosis and treatment of children with severe combined immunodeficiency. DEVELOPED: Public organization National Society of Pediatric Hematologists, Oncologists; FGBU "FNKTs DGOI them. Dmitry Rogachev" of the Ministry of Health of Russia. Rumyantsev A.G., Maschan A.A., Shcherbina A.Yu. Official edition. Moscow. 2015. 28 p.];
23. Федеральные клинические рекомендации по диагностике и лечению синдрома делеции 22 хромосомы. РАЗРАБОТАН: Общественная организация Национальное общество детских гематологов, онкологов; ФГБУ «ФНКЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Румянцев А.Г., Масчан А.А., Щербина А.Ю. Издание официальное. Москва. 2015. 12 с. [Federal clinical guidelines for the diagnosis and treatment of chromosome 22 deletion syndrome. DEVELOPED: Public organization National Society of Pediatric Hematologists, Oncologists; FGBU "FNKTs DGOI them. Dmitry Rogachev" of the Ministry of Health of Russia. Rumyantsev A.G., Maschan A.A., Shcherbina A.Yu. Official edition. Moscow. 2015. 12 p].