SELECTIVE SCREENING FOR IMMUNE DISORDERS IN NEWBORN AND INFANT CHILDREN

DOI: https://doi.org/10.29296/24999490-2023-02-06

L.Yu. Popova(1), G.D. Alemanova(1), I.N. Chainikova(1), D.A. Kudlay(2, 3), E.A. Zlodeeva(1), A.A. Albakasova(1),
1-FGBOU VO «Orenburg State Medical University» of the Ministry
of Health of Russia, st. Sovetskaya, d. 6, Orenburg, 460000, Russian Federation;
2-FGBOU VO First Moscow State Medical University. THEM. Sechenov of the Ministry
of Health of Russia (Sechenov University), st. Trubetskaya, d.8, building 2, Moscow, 119991, Russian Federation;
3-FGBOU GNTS Institute of Immunology” FMBA of Russia, Kashirskoe shosse, 24, Moscow, 115522, Russian Federation

Introduction. Primary immunodeficiency states (PIDs) are a heterogeneous group of innate immune disorders. A feature of the clinical manifestations of PID is that they are nonspecific for specific clinical forms. With untimely diagnosis and the absence of pathogenetic therapy for immunodeficiencies, an unfavorable outcome is likely. From these positions, a modern method for diagnosing PID using multiplex analysis of the amount of TREC and KREC in dry blood spots in newborns and young children is relevant. The purpose of the study: a comparative analysis of the amount of TREC and KREC in dry blood spots in children at risk for primary immunodeficiency (PID) under the age of 2 years as markers of T- and B-cell immune defects. Methods. Markers of T-cell (TREC) and B-cell (KREC) immunodeficiencies were identified in 112 children from the PID risk group under the age of 2 years. The number of copies of TREC and KREC was determined by real-time PCR. Phenotyping of lymphocytes was carried out by flow cytometry. Results. In 98 children (87.5%) out of 112 examined, the levels of TREC and KREC did not differ from the reference values. In 14 (12.5%) of children, a decrease in the level of TREC compared with the norm (p
Keywords: 
children, immunodeficiency, screening, TREC, KREC, premature

Список литературы: 
  1. Notarangelo L.D., Bacchetta R., Casanova J.L., Su H.C. Human inborn errors of immunity: An expanding universe. Sci. Immunol. 2020; 5: eabb1662. DOI: 10.1126/sciimmunol.abb1662
  2. Blom M., Bredius R.G.M., van der Burg M. Future Perspectives of Newborn Screening for Inborn Errors of Immunity. International journal of neonatal screening. 2021; 7 (4): 74. DOI.org/10.3390/ijns7040074
  3. Kutlug S., Karadag Alpaslan, Hancioglu M., ElifOzyaziciOzkan G., CemileYesilirmak S., Bulut D., Aygun H., Ogur C., Yildiran G. & A. Multiplex PCR-Based Newborn Screening for Severe T and B-Cell Lymphopenia: The first Pilot Study in Turkey. SisliEtfalHastanesitipbulteni. 2021; 55 (4): 551–9. DOI.org/10.14744/SEMB.2020.09623
  4. Picard C., Al-Herz W., Bousfiha A., Casanova J.L., Chatila T., Conley M.E. et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for primary immunodeficiency. J. ClinImmunol. 2015; 35 (8): 696–726. DOI: 10.1007/s10875-015-0201-1.
  5. Щербина А.Ю. Маски первичных иммунодефицитных состояний: проблемы диагностики и терапии. Российский журнал детской гематологии и онкологии. 2016; 3 (1): 52–8. [Shcherbina A.Yu. Masks of primary immunodeficiency disorders: diagnostic and therapeutic problems. Russian J. of Children Hematology and Oncology. 2016; 3: 52–8 (in Russian)].
  6. Чернышова Е.В., Анастасевич Л.А., Щербина А.Ю., Ларин С.С. Современные возможности скрининга и диагностики первичных иммунодефицитных состояний в педиатрии. Педиатрия. 2016; 95 (5): 121–8. [Chernyshova E.V., Anastasevich L.A., Shcherbina A.Yu., Larin S.S. Modern possibilities of screening and diagnostics of primary immunodeficiency states in pediatrics. Pediatrics. 2016; 95 (5): 121–8 (in Russian)].
  7. Латышева Е.А. Первичные иммунодефициты: состояние проблемы на сегодняшний день. JMF-центры в России. Вопросы современной педиатрии. 2013; 12 (6): 73–5. [Latysheva E.A. Primary immunodeficiencies: the state of the problem today. JMF-centers in Russia. Questions of modern pediatrics. 2013; 12 (6): 73–5 (in Russian)].
  8. Ярцев М.Н., Яковлева К.П., Плахтиенко М.В. Первичная иммунная недостаточность по данным Регистра первичных иммунодефицитных состояний Института иммунологии ФМБА России. Педиатрия. Приложение к журналу Consilium Medicum. 2006; 8 (1): 4–9. [Yartsev M.N., Yakovleva K.P., Plakhtienko M.V. Primary immune deficiency according to the Register of Primary Immunodeficiency States of the Institute of Immunology of the Federal Medical and Biological Agency of Russia. Pediatrics. Attachement to the magazine Consilium Medicum. 2006; 8 (1): 4–9 (in Russian)].
  9. Кондратенко И.В. Первичные иммунодефициты. Медицинская иммунология. 2005; 7 (5–6): 467–76. [Kondratenko I.V. Primary immunodeficiencies. Medical Immunology. 2005; 7 (5–6): 467–76 (in Russian)].
  10. 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 DOI: 10.24110/0031-403X-2020-99-2-8-15 [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. DOI: 10.24110/0031-403X-2020-99-2-8-15 (in Russian)].
  11. Зайцева Е.В., Запарий В.В. Современное состояние вопроса диагностики и лечения первичных иммунодефицитов. Современные проблемы науки и образования. 2020; 5: 139. [Zaitseva E.V., Zapariy V.V. The current state of the issue of diagnosis and treatment of primary immunodeficiencies. Modern problems of science and education. 2020; 5: 139 (in Russian)].
  12. King J.R., Hammarström, L. Newborn Screening for Primary Immunodeficiency Diseases: History, Current and Future Practice. Journal of clinical immunology. 2018. 38 (1): 56–66. DOI.org/10.1007/s10875-017-0455-x
  13. Cristina G.M., Anne T., Katja V., Markku J., David M.H., Jonas B.G., Marie B.H., Dea A., Galina F., Stephanie D., David G., Daniel S. Rongcong. Wu: Development of a Multiplex Real-Time PCR Assay for the Newborn Screening of SCID, SMA, and XLA. Int. J. Neonatal Screen. 2019; 5: 39. DOI.org/10.3390/ijns5040039
  14. Shinwari K., Bolkov M., Tuzankina I.A. & Chereshnev V.A. Newborn Screening through TREC, TREC/KREC System for Primary Immunodeficiency with limitation of TREC/KREC. Comprehensive Review. Anti-inflammatory & anti-allergy agents in medicinal chemistry. 2021; 20 (2): 132–49. DOI.org/10.2174/1871523019999200730171600
  15. 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; 20 (1): 85–98. DOI: 10.15789/1563-0625-2018-1-85-98. [Deryabina S.S., Tuzankina I.A., Shershnev V.N. Determination of reference values for TREC and KREC in dry blood spots of newborns from different gestation ages in Sverdlovsk Region. Meditsinskaya immunologiya. Medical Immunology Russia. 2018; 20 (1): 85–98. DOI.org/10.15789/1563-0625-2018-1-85-98 (in Russian)].
  16. Borte S., von Dobeln U., Fasth A. et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012; 119 (11): 2552–5. DOI:10.1182/blood-2011-08-371021
  17. Nakagava N., Imai K., Kanegane H. et al. Quantification of k-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects. J. Allergy ClinImmunol. 2011; 128 (1): 223–5. e2. DOI: 10.1016/j.jaci.2011.01.052.
  18. Дерябина С.С., Тузанкина И.А., Власова Е.В., Лаврина С.Г., Шершнев В.Н. Ретроспективная диагностика первичных иммунодефицитных состояний у детей в Свердловской области. Медицинская иммунология. 2016; 18 (6): 583–8. [Deryabina S.S., Tuzankina I.A., Vlasova E.V., Lavrina S.G., Shershnev V.N. Retrospective diagnosis of primary immunodeficiency states in children in the Sverdlovsk region. Medical Immunology. 2016; 18 (6): 583–8 (in Russian)].
  19. Тузанкина И.А., Дерябина С.С., Болков М.А., Басс Е.А., Власова Е.В., Крохалева Я.М., Шершнев В.Н. Первичные иммунодефициты в раннем возрасте. М., 2018; 176. [Tuzankina I.A., Deryabina S.S., Bolkov M.A., Bass E.A., Vlasova E.V., KrokhalevaYa.M., Shershnev V.N. Primary immunodeficiencies at an early age. Moscow, 2018; 176 (in Russian)].
  20. Kwan A., Abraham R.S., Currier R., Brower A., Andruszewski K., Abbott J.K. et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014; 312 (7): 729–38. DOI: 10.1001/jama.2014.9132
  21. Chien Y.-H., Yu H.-H., Lee N.-C., Ho H.-C., Kao S.-M., Lu M.-Y. et al. Newborn screening for severe combined immunodeficiency in Taiwan. Int J. Neonatal Screen. 2017; 3 (3): 16. DOI: 10.3390/ijns3030016.
  22. Zetterström R., Barbaro M., Ohlsson A., Borte S., Jonsson S., Winiarski J. et al. Newborn screening for primary immune deficiencies with a TREC/KREC/ACTB triplex assay-a three-year pilot study in Sweden. Int J. Neonatal Screen. 2017; 3 (2): 11. DOI: 10.3390/ijns3020011.
  23. Нисиченко О.А., Минулин И.Р., Семенова В.В. Диагностика синдрома Ниймеген у пациента с рабдомиосаркомой на этапе реабилитации. Педиатрический вестник Южного Урала. 2021; 2: 144–50. [Nisichenko O.A., Minulin I.R., Semenova V.V. Diagnosis of Nijmegen syndrome in patients with rhabdomyosarcoma at the rehabilitation stage. Pediatricheskij vestnik YUzhnogo Urala. 2021; 2: 144–50 (in Russian)].
  24. Козлов В.А., Савченко А.А., Кудрявцев И.В., Козлов И.Г., Кудлай Д.А., Продеус А.П., Борисов А.Г. Клиническая иммунология. Красноярск, 2020; 386. [Kozlov V.A., Savchenko A.A., Kudryavcev I.V., Kozlov I.G., Kudlay D.A., Prodeus A.P., Borisov A.G. Clinical immunology. Krasnoyarsk, 2020; 386 (in Russian)].
  25. Корсунский И.А., Продеус А.П., Румянцев А.Г., Гордукова М.А., Корсунский А.А., Кудлай Д.А., Филипенко М.Л., Шустер А.М. Скрининг новорожденных на первичные иммунодефициты и группу риска иммунорегуляторных расстройств, требующих диспансерного наблюдения. Педиатрия. 2019; 98 (3): 49–54. [Korsunsky I.A., Prodeus A.P., Rumyantsev A.G., Gordukova M.A., Korsunsky A.A., Kudlay D.A., Filipenko M.L., Schuster A.M.. Screening of newborns for primary immunodeficiencies and risk groups for immunoregulatory disorders requiring follow-up. Pediatria. 2019; 98 (3): 49–54. https://doi.org/10.24110/0031-403X-2019-98-3-49-54 (in Russian)].
  26. Тузанкина И.А., Дерябина С.С., Власова Е.В., Болков М.А. Семейный случай синдрома Ди Джорджи (синдрома делеции 22q11.2). Медицинсккая иммунология. 2017; 19 (1): 95–100. [Tuzankina I.A., Deryabina S.S., Vlasova E.V., Bolkov M.A. Semeyniy sluchai sindroma Di Dzhordzhi (sindroma deletsil 22q11.2). Meditsinskaya Immunologiya. Medical Immunology. 2017; 19 (1): 95–100. DOI.org/:10.15789/1563-0625-2017-1-95-100 (in Russian)].