TREC and KREC in newborns of different gestational age
- Authors: Ippolitova L.I.1,2,3,4, Ivantsova E.N.1,2,3,4, Kudlay D.A.1,2,3,4, Panichev K.V.1,2,3,4, Kokoreva S.P.1,2,3,4
-
Affiliations:
- Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation
- Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
- National Research Center – Institute of Immunology of the Federal Medical-Biological Agency
- 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
- Issue: Vol 21, No 3 (2023)
- Pages: 65-72
- Section: Original research
- URL: https://journals.eco-vector.com/1728-2918/article/view/568249
- DOI: https://doi.org/10.29296/24999490-2023-03-09
- ID: 568249
Cite item
Open Access
Access granted
Abstract
Introduction. Primary immunodeficiency (PID) is a congenital disorder of the immune system that causes severe, chronic, autoimmune, infectious and oncological diseases with untimely diagnosis and treatment. Given that PIDs often do not have specific clinical manifestations, patients with this group of diseases are detected quite late, as a result of which the complications obtained can no longer be cured within the framework of standard treatment protocols. Thus, the introduction of additional studies into the neonatal screening program to determine the state of the T- and B-cell immunity link will avoid the development of severe complications in children with PID and will allow timely treatment to begin.
The aim of the study is to determine the TREC and KREC levels and their relationship with other indicators in newborns of different gestational ages..
Methods. This paper presents the results of the pilot program of neonatal screening of primary immunodeficiency in Voronezh and the Voronezh region. Markers of T- and B-cell lymphopoiesis were determined in 126 newborns by quantifying ring DNA molecules TREC and KREC by PCR-RV from dry blood spots on the basis of BUZ VOKB No. 1 PC, Building 1. Criteria such as gender, gestational age, body weight, total blood count (leukocyte count) at admission and closest to neonatal screening, CRP at admission and closest to neonatal screening, the presence of a burdened somatic and obstetric-gynecological history were evaluated; as a result, the main patterns in the dynamics of the KREC level were deduced and TREC in the study groups. Blood samples were obtained during the standard newborn screening program by collecting heel blood on special filter paper test forms – Guthrie cards.
Results. TREC and KREC levels increase with increasing gestation period, however, in all premature infants they remain below the established standard values. A significant increase in the detected indicators is observed precisely during the last weeks of intrauterine life. Evaluating the «body weight» indicator, it was found that the most frequently reduced levels of TREC and KREC were observed in newborns with a body weight of 1500–2000 g, less often in newborns weighing more than 2500 g. When evaluating the indicator «burdened obstetric and gynecological (OAG) and burdened somatic anamnesis (OSA)», it was revealed that in all selected groups, in 100% of cases, newborns had a history of OAG and OSA. Evaluating other compared criteria, it was found that the most frequently reduced levels of TREC and KREC were observed in newborns at 29–32 weeks gestation.
Conclusion. The dynamics of increasing the level of TREC and KREC increases with increasing gestation period and body weight, and already at 29–32 weeks (with a weight of more than 1500 g) becomes the most informative due to the fact that the pool of cells responsible for the implementation of cellular and humoral immunity can most adequately respond to various significant effects on the body.
Keywords
Full Text
About the authors
Lyudmila I. Ippolitova
Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology of the Federal Medical-Biological Agency; 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
Email: ippolitovaliuda@yandex.ru
ORCID iD: 0000-0001-7076-0484
doctor of Medical Sciences, head of the Department of Neonatology and Pediatrics of the Voronezh State Medical University named after N.N. Burdenko, Ministry of Health of the Russian Federation, chief freelance neonatologist of the Voronezh Region
Russian Federation, Studencheskaya st., 10, Voronezh, 394036; st. Trubetskaya, 8, building 2, Moscow, 119435; Kashirskoye highway, 24, Moscow, 115522; Moskovsky Ave, 151, Voronezh, 394066Elena N. Ivantsova
Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology of the Federal Medical-Biological Agency; 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
Email: elena.iwanczowa-lena@yandex.ru
ORCID iD: 0000-0001-8979-3454
resident of the Department of Neonatology and Pediatrics of the Voronezh State Medical University named after N.N. Burdenko, Ministry of Health of the Russian Federation
Russian Federation, Studencheskaya st., 10, Voronezh, 394036; st. Trubetskaya, 8, building 2, Moscow, 119435; Kashirskoye highway, 24, Moscow, 115522; Moskovsky Ave, 151, Voronezh, 394066Dmitry A. Kudlay
Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology of the Federal Medical-Biological Agency; 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
Email: d624254@gmail.com
ORCID iD: 0000-0003-1878-4467
MD, сorr. member of the RAS, prof. of the Dep. of Pharmacology, Institute of Pharmacy of I.M. Sechenov First Moscow State Medical University (Sechenov University)) of the MOH of Russia, leading res. at the laboratory of personalized medicine and molecular immunology NRC Institute of Immunology FMBA of Russia
Russian Federation, Studencheskaya st., 10, Voronezh, 394036; st. Trubetskaya, 8, building 2, Moscow, 119435; Kashirskoye highway, 24, Moscow, 115522; Moskovsky Ave, 151, Voronezh, 394066Konstantin V. Panichev
Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology of the Federal Medical-Biological Agency; 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
Email: panvor@mail.ru
ORCID iD: 0000-0002-3388-8291
head of the Neonatal Intensive Care Unit № 5 of the Voronezh Region Budget Healthcare Institution «Voronezh Regional Clinical Hospital No.1», Perinatal Center
Russian Federation, Studencheskaya st., 10, Voronezh, 394036; st. Trubetskaya, 8, building 2, Moscow, 119435; Kashirskoye highway, 24, Moscow, 115522; Moskovsky Ave, 151, Voronezh, 394066Svetlana P. Kokoreva
Federal State Budgetary Educational Institution of Higher Education «Voronezh State Medical University named after N. N. Burdenko», Ministry of Health of the Russian Federation; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); National Research Center – Institute of Immunology of the Federal Medical-Biological Agency; 4Budgetary Healthcare Institution of the Voronezh Region «Voronezh Regional Clinical Hospital №1», Perinatal Center
Author for correspondence.
Email: Kokorevasp@mail.ru
ORCID iD: 0000-0002-3387-9803
doctor of Medical Sciences, head of the Department of Infectious Diseases of the N.N. Burdenko State Medical University of the Ministry of Health of Russia
Russian Federation, Studencheskaya st., 10, Voronezh, 394036; st. Trubetskaya, 8, building 2, Moscow, 119435; Kashirskoye highway, 24, Moscow, 115522; Moskovsky Ave, 151, Voronezh, 394066References
- Полякова Е., Стеганцева М., Гурьянова И., Сакавич И., Белевцев М. Кольцевые молекулы Т- и В-клеточного рецепторов (TREC/KREC) в дифференциальной диагностике первичных иммунодефицитов. Наука и инновации. 2019; 1 (8): 75–8. doi: 10.29235/18189857201987578 [Polyakova E., Stegantseva M., Guryanova I., Sakavich I., Belevtsev M. T and B cell receptor circle molecules (TREC/KREC) in the differential diagnosis of primary immunodeficiencies. Nauka i innovatsii. 2019; 1 (8): 75–8. doi: 10.29235/18189857201987578 (in Russian)]
- Picard C., Al-Herz W., Bousfiha A., Casanova J. L., Chatila T., Conley M. E., Cunningham-Rundles C., Etzioni A., Holland S. M., Klein C., Nonoyama S., Ochs H. D., Oksenhendler E., Puck, J. M., Sullivan K. E., Tang M. L., Franco J. L., Gaspar H. B. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency. J. of clinical immunology. 2015; 35 (8): 696–726. doi: 10.1007/s10875-015-0201-1.
- Корсунский И.А., Кудлай Д.А., Продеус А.П., Щербина А.Ю., Румянцев А.Г. Неонатальный скрининг на первичные иммунодефицитные состояния и Т-/В-клеточные лимфопении как основа формирования групп риска детей с врожденными патологиями. Педиатрия им. Г.Н. Сперанского. 2020; 99 (2): 8–15. https://doi.org/10.24110/0031-403X-2020-99-2-8-15I.A. [Korsunsky I.A., Kudlay D.A., Prodeus A.P., Shcherbina A.Yu., Rumyantsev A.G. Neonatal screening for primary immunodeficiency and Т-/B-cell lymphopenia as the basis for the formation of risk groups for children with congenital pathologies. Pediatria n.a. G.N. Speransky. 2020; 99 (2): 8–15. https://doi.org/10.24110/0031-403X-2020-99-2-8-15 (in Russian)]
- Kwok J.S.Y., Cheung S.K.F., Ho J.C.Y., Tang I.W.H., Chu P.W.K., Leung E.Y.S., Lee P.P.W. Cheuk D.K.L., Lee V., Ip P., Lau Y.L. 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; 16 (11): 1411–23. doi: 10.3389/fimmu.2020.01411
- Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O’Shea J.J. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCIN). Nature. 1995; 377 (6544): 65–8. doi: 10.1038/377065a0
- Kanegane H., Imai K., Morio T. Severe Combined Immunodeficiency – from Discovery to Newborn Screening. Currier, in Primary Immunodeficiency Disorders. 2017; 40 (3): 145–54. doi: 10.2177/jsci.40.145.
- 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; 8 (2): 143–52. doi: 10.18502/ijaai.v18i2.917
- Barbaro M., Ohlsson, A., Borte, S., Jonsson, S., Zetterström, R.H., King, J., Winiarski, J., von Döbeln, U., Hammarström, L. Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year Pilot TREC and KREC Screening Study. J. Clin. Immunol. 2017; 37 (1): 51–60. doi: 10.1007/s10875-016-0347-5
- Тузанкина И.А., Дерябина С.С., Болков М.А., Власова Е.В., Крохалева Я.М., Черемохин Д.А., Арипова Т.У., Мусаходжаева Д.А., Камалов З.С. Первичные иммунодефициты (врожденные ошибки иммунитета) в раннем возрасте: монография. Ташкент: Adast-poligraf, 2022; 232. [Tuzankina I.A., Deryabina S.S., Bolkov M.A., Vlasova E.V., Krokhaleva Ya.M., Cheremokhin D.A., Aripova T.U., Musakhodzhaeva D.A., Kamalov Z.S. Primary immunodeficiency (innate errors of immunity) in early age]. Tashkent: Adast-poligraf, 2022, 232 (in Russian)]
- Nourizadeh M., Shakerian L., Borte S., Fazlollahi M., Badalzadeh M., Houshmand M., Alizadeh Z., Dalili H., Rashidi-Nezhad A., Kazemnejad A., Moin M., Hammarström L., Pourpak Z. Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran. Scand J. Immunol. 2018; e12699 (128): 516–23. doi: 10.1111/sji.12699.
- Черемохин Д.А., Шинвари Х., Дерябина С.С., Болков М.А., Тузанкина И.А., Кудлай Д.А. Анализ уровней TREС и KREC в образцах сухой крови новорожденных разного гестационного возраста и веса. Acta Naturae. 2022; 14 (1): 101–8. doi: 10.32607/actanaturae.11501 [Cheremokhin D.A., Shinwari K., Deryabina S.S., Bolkov M.A., Tuzankina I.A., Kudlay D.A. Analysis of the TREC and KREC Levels in the Dried Blood Spots of Healthy Newborns with Different Gestational Ages and Weights. Acta Naturae. 2022; 14 (1): 101–8. doi: 10.32607/actanaturae.11501 (in Russian)]
- Гордукова М.А., Корсунский И.А., Чурсинова Ю.В., Бяхова М.М., Оскорбин И.П., Продеус А.П., Филипенко М.Л. Определение референсных интервалов TREC и KREC для скрининга новорожденных с иммунодефицитными состояниями в РФ. Медицинская иммунология. 2019; 21 (3): 527–38. https://doi.org/10.15789/1563-0625-2019-3-527-538 [Gordukova M.A., Korsunsky I.A., Chursinova Yu.V., Byakhova M.M., Oscorbin I.P., Prodeus A.P., Filipenko M.L. Determining reference ranges for TREC and KREC assays in immune deficiency screening of newborns in Russian Federation. Medical Immunology (Russia). 2019; 21 (3): 527–38. https://doi.org/10.15789/1563-0625-2019-3-527-538 (in Russian)]
- Inborn Errors of Immunity Committee (IEI) https://iuis.org/committees/iei/ (дата обращения 27.03.2023).
- Барычева Л.Ю., Хачирова Л.С., Кубанова Л.Т., Душина Л.В., Мухина А.А. Регистр первичных иммунодефицитов в Ставропольском крае. Медицинский вестник Северного Кавказа. 2019; 14 (4): 693–5. https://doi.org/10.14300/mnnc.2019.14171 [Barycheva L.Yu., Khachirova L.S., Kubanova L.T., Dushchina L.V., Mukhina A. A. Register of primary immunodeficiency in the Stavropol territory. Medical News of North Caucasus. 2019; 14 (4): 693–5. https://doi.org/10.14300/mnnc.2019.14171 (in Russian)]
- Gaspar H.B., Hammarström L., Mahlaoui N., Borte M., Borte S. The case for mandatory newborn screening for severe combined immunodeficiency (SCID). J. Clin. Immunol. 2014; 24 (4): 393–7. DOI: 10.1007/ s10875-014-0029-0
- Speckmann C., Neumann C., Borte S., la Marca G., Sass J.O., Wiech E., Fisch P., Schwarz K., Buchholz B., Schlesier M., Felgentreff K., Grimbacher B., Santisteban I., Bali P., Hershfield M. S., Ehl S. Delayed-onset adenosine deaminase deficiency: strategies for an early diagnosis. J. Allergy Clin. Immunol. 2012; 130 (4): 991–4. DOI: 10.1016/ j.jaci.2012.04.004
- Образцов И.В., Гордукова М.А., Северина Н.А., Бидерман Б.В., Смирнова С.Ю., Судариков А.Б., Никитин Е.А., Румянцев А.Г. Эксцизионные кольца V(D)J-рекомбинации B- и T-клеток как прогностический маркер при В-клеточном хроническом лимфолейкозе. Клиническая онкогематология. 2017; 10 (2): 131–40. doi: 10.21320/2500-2139-2017-10-2-131-140 [Obraztsov I.V., Gordukova M.A., Severina N.A., Biderman B.V., Smirnova S.Yu., Sudarikov A.B., Nikitin E.A., Rumyantsev A.G. V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia. Clinical oncohematology. 2017; 10 (2): 131–40. doi: 10.21320/2500-2139-2017-10-2-131-140 (in Russian)]
- Козлов В.А., Тихонова Е.П., Савченко А.А., Кудрявцев И.В., Андронова Н.В., Анисимова Е.Н., Головкин А.С., Демина Д.В., Здзитовецкий Д.Э., Калинина Ю.С., Каспаров Э.В., Козлов И.Г., Корсунский И.А., Кудлай Д.А., Кузьмина Т.Ю., Миноранская Н.С., Продеус А.П., Старикова Э.А., Черданцев Д.В., Чесноков А.Б. и др. Клиническая иммунология. Практическое пособие для инфекционистов. Красноярск: Поликор, 2021; 563. doi: 10.17513/np.518 [Kozlov V.A., Tikhonova E.P., Savchenko A.A., Kudryavtsev I.V., Andronova N.V., Anisimova E.N., Golovkin A.S., Demina D.V., Zdzitovetsky D. .E., Kalinina Yu.S., Kasparov E.V., Kozlov I.G., Korsunsky I.A., Kudlai D.A., Kuzmina T.Yu., Minoranskaya N.S., Prodeus A.P. ., Starikova E.A., Cherdantsev D.V., Chesnokov A.B., P.A. Gear, A.G. Borisov. Clinical immunology. A practical guide for infectious disease specialists. Krasnoyarsk: Polikor, 2021; 563. doi: 10.17513/np.518 (in Russian)]
- Исакова С.С., Урозаев О.Н., Бекмухамбетов Е.Ж. Значение определения TREC (T-cell receptor excision circles) в диагностике и прогнозировании заболеваний. Наука и здравоохранение. 2013; 6 (1): 13–6. [Isakova S.S., Urozaev O.N., Bekmukhambetov E.Zh. The value of determining TREC (T-cell receptor excision circles) in the diagnosis and prognosis of diseases. Nauka i zdravookhraneniye. 2013; 6 (1): 13–6 (in Russian)]
Supplementary files
