LABORATORY CRITERIA FOR IMPROVING THE DIAGNOSIS OF AUTOIMMUNE HEPATITIS AND WILSON'S DISEASE IN CHILDREN



Cite item

Full Text

Abstract

Abstract

The definition of laboratory criteria for improving the differential diagnosis of children with autoimmune hepatitis (AIH) and Wilson's disease (WD) is relevant in pediatrics. One of the criteria for the diagnosis of AIH is an increase in the titers of the antinuclear factor (ANF) in the blood serum. Cases have been described when WD can clinically occur as autoimmune hepatitis (AIH) with the detection of non-specific autoantibodies, which complicates differential diagnosis. The aim of the study was to identify the features of the determination of antinuclear factor on the Hep–2 cell line and specific autoantibodies using a triple substrate in children with autoimmune hepatitis and WD. Materials and methods: 62 children with WD and 28 children with AIH were examined. ANF was determined on the HEp-2 cell line (ANA-HEp-2, AESKUSLIDES®, Germany) and specific autoantibodies using a triple substrate obtained from rodents, which includes samples of kidney, liver and stomach tissues (LKS Mouse, Germany) using indirect fluorescence reactions using an automatic analyzer HELIOS® (Germany). Results: The analysis revealed positive results of the ANF study in 15 out of 62 (24%) children with WD. Positive ANF results were obtained in 26 out of 28 children(93%) with AIH, significantly more often ANF is detected in children with AIH compared with WD. The study of specific autoantibodies using a triple substrate revealed positive results in 34 children with WD (55%) and 26 children with AIH (93%), significantly more often specific autoantibodies on the triple substrate are detected in children with AIH(p<0.001) than in children with WD. Conclusion: when examining a child with suspected AIH, when a homogeneous type of luminescence is detected on the HEp-2 cell line and with a combination of different types of luminescence on a triple substrate, the presence of WD in patients cannot be excluded.

About the authors

Anastasia A. Zhuzhula

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: Anas-zh@inbox.ru
ORCID iD: 0000-0002-6292-7229
SPIN-code: 8783-9571
Scopus Author ID: 57226395657
ResearcherId: AGU-5991-2022

Junior Researcher at the Laboratory of Experimental Immunology and Virology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1Moscow 119991

Olga V. Kurbatova

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: putintseva@mail.ru
ORCID iD: 0000-0002-9213-5281

Ph.D. (Medicine), Senior Researcher, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1, Lomonosov Ave, Moscow, 119296

S. V. Petrichuk

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: cito@list.ru
ORCID iD: 0000-0003-0896-6996

PhD, MD (Biology), Professor, Chief Research Associate, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1, Lomonosovsky prospect., Moscow, 119296

A. P. Fisenko

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: Putintseva@mail.ru

PhD, MD (Medicine), Professor, Head

Russian Federation, Moscow

Marina A. Snovskaya

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: snows@inbox.ru
ORCID iD: 0000-0002-5263-6743
SPIN-code: 9899-1095
Scopus Author ID: 56515506400

Ph.D. (Medicine), Senior Researcher at the Laboratory of Experimental Immunology and Virology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1Moscow 119991

Goar B. Movsisyan

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation

Email: movsisyan@nczd.ru
ORCID iD: 0000-0003-2881-4703

Senior Researcher of the Laboratory of Rare Hereditary Diseases, Gastroenterologist of the Gastroenterology Department with the Hepatological Group

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Alexander S. Potapov

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation;
Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: potapov@nczd.ru
ORCID iD: 0000-0003-4905-2373

PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Scientific Foundations of Pediatric Gastroenterology and Hepatology, Head of the Center for Inflammatory Bowel Diseases in Children, Head of Gastroenterology Department with Hepatology Group, National Medical Research Center for Children’s Health, Professor, Department of Pediatrics and Pediatric Rheumatology

Russian Federation, 1/2, Lomonosovskiy Pr-t, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991

Elena L. Semikina

FSAU "NMIC of Children's Health" of the Ministry of Health of the Russian Federation;
Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Author for correspondence.
Email: semikinaelena@yandex.ru
ORCID iD: 0000-0001-8923-4652

PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Research in Pediatric Gastroenterology and Hepatology, Head of Gastroenterology Department with Hepatology Group, Professor, Department of Pediatrics and Pediatric Rheumatology

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991; 8/2, st. Trubetskaya, Moscow, 119991

References

  1. Григорьев КИ, Выхристюк ОФ (2022). Аутоиммунный гепатит у детей. Лечебное дело, (3-4), 4-13. Grigoriev KI, Vykhristyuk OF (2022). Autoimmune hepatitis in children. Lechebnoe delo = The Journal of General Medicine, (3-4), 4-13. doi.:10.24412/2071-5315-2022-12913
  2. Жужула А.А., Курбатова О.В., Сновская М.А., Фисенко А.П., Петричук С.В., Коноплева Т.Н., Семикина Е.Л. Специфические антинуклеарные антитела при разных типах свечения антинуклеарного фактора на клеточной линии HEp-2 у детей с аутоиммунными заболеваниями // Российский иммунологический журнал. - 2025. - Т. 28. - №2. - C. 247-254. Zhuzhula A.A., Kurbatova O.V., Snovskaya M.A., Fisenko A.P., Petrichuk S.V., Konopleva T.N., Semikina E.L. Specific antinuclear antibodies in different fluorescence patterns of antinuclear factor on the HEp-2 cell line in children with autoimmune diseases // Russian Journal of Immunology. - 2025. - Vol. 28. - N. 2. - P. 247-254. doi: 10.46235/1028-7221-17038-SAA
  3. Жужула А.А., Курбатова О.В., Петричук С.В., Парахина Д.В., Сновская М.А., Мовсисян Г.Б., Семикина Е.Л., Потапов А.С., Фисенко А.П. Диагностическая значимость определения антинуклеарных антител у детей с аутоиммунным гепатитом. Аллергология и Иммунология в Педиатрии. 2024;(1):36-40.
  4. Zhuzhula A.A., Kurbatova O.V., Petrichuk S.V., Parakhina D.V., Snovskaya M.A., Movsisyan G.B., Semikina E.L., Potapov A.S., Fisenko A.P. Diagnostic significance of the determination of antinuclear antibodies in children with autoimmune hepatitis. Allergology and Immunology in Paediatrics. 2024;(1):36-40.
  5. https://doi.org/10.53529/2500-1175-2024-1-36-40
  6. Курбатова О.В., Жужула А.А., Лапин С.В., Сновская М.А., Козлова Д.И., Петричук С.В., Купцова Д.Г., Кузнецова Д.А., Мовсисян Г.Б., Комарова А.Д., Радыгина Т.В., Гуслев А.Б., Холопова И.В., Семикина Е.Л., Макарова С.Г., Потапов А.С., Фисенко А.П. Антинуклеарные антитела у детей с болезнью Вильсона. Аллергология и Иммунология в Педиатрии. 2024;(1):48-52. Kurbatova O.V., Zhuzhula A.A., Lapin S.V., Snovskaya M.A., Kozlova D.I., Petrichuk S.V., Kuptsova D.G., Kuznetsova D.A., Movsisyan G.B., Komarova A.D., Radygina T.V., Guslev A.B., Kholopova I.V., Semikina E.L., Makarova S.G., Potapov A.S., Fisenko A.P. Antinuclear antibodies in children with Wilson’s disease. Allergology and Immunology in Paediatrics. 2024;(1):48-52. https://doi.org/10.53529/2500-1175-2024-1-48-52
  7. Курбатова О. В., Мовсисян Г. Б., Петричук С. В. [и др.] Показатели клеточного иммунитета и метаболизм лимфоцитов у детей с аутоиммунным гепатитом первого типа при разных стадиях фиброза печени // Иммунопатология, аллергология, инфектология. – 2024. – № 2. – С. 75-83. Kurbatova O. V., Movsesyan G. B., Petrichuk S. V. [et al.] Indicators of cellular immunity and lymphocyte metabolism in children with type I autoimmune hepatitis at different stages of liver fibrosis // Immunopathology, allergology, infectology. - 2024. – No. 2. – pp. 75-83. doi: 10.14427/jipai.2024.2.75. – EDN ROMCSW.
  8. Курбатова ОВ, Мовсисян ГБ, Петричук СВ, Парахина ДВ, Демьянов ДC, Купцова ДГ, Радыгина ТВ, Семикина ЕЛ, Потапов АС, Фрейдлин ЕВ. Информативность лабораторных маркеров в оценке стадии фиброза печени у детей с аутоиммунным гепатитом первого типа. Аллергология и иммунология в педиатрии. 2023; 1: 53–55. Kurbatova OV, Movsisyan GB, Petrichuk SV, Parakhina DV, Demyanov DS, Kuptsova DG, Radygina TV, Semikina EL, Potapov AS, Freidlin EV. Informative value of laboratory markers in assessing the stage of liver fibrosis in children with type 1 autoimmune hepatitis. Allergology and Immunology in Paediatrics. 2023; (1): 53–55. (In Russ.) https://doi.org/10.53529/2500-1175-2023-1-53-55.
  9. Рекомендации EASL по лечению аутоиммунного гепатита // J of Hepatol. Русское издание. — 2015. — Vol.63, № 5. — P. 111–150. EASL recommendations for the treatment of autoimmune hepatitis. J of Hepatol. Russian edition. 2015, Vol. 63, No. 5, pp. 111–150.] https://easl.eu/wp-content/uploads/2018/10/2015-AIH_RU.pdf
  10. Союз педиатров России Федеральные клинические рекомендации «Нарушения обмена меди (болезнь Вильсона) 2014 г. https://cr.minzdrav.gov.ru/view-cr/376_3 Russian Union of Pediatricians Federal Clinical Guidelines "Copper metabolism Disorders (Wilson's disease) 2014 https://cr.minzdrav.gov.ru/view-cr/376_3
  11. Фисенко А.П., Сурков А.Н., Потапов А.С. Болезнь Вильсона у детей. М: НМИЦ здоровья детей, 2019. — C. 84 Fisenko AP, Surkov AN, Potapov AS. Wilson’s disease in children. M: National Medical Research Center for Children’s Health, 2019. — P.84. (In Russ.) https://nczd.ru/wp-content/uploads/2023/07/bol-vilson-2019-1.pdf
  12. Циммерман Я.С. Болезнь Вильсона — гепатоцеребральная дистрофия. Клиническая медицина. 2017; 4: 310–315. Zimmerman JS. Wilson’s disease — hepatocerebral dystrophy. Clinical medicine. 2017; 4: 310–315. (In Russ.) http://dx.doi.org/10.18821/0023-2149-2017-95-4-310-315.
  13. Юсупов, Ф.А. Болезнь Вильсона-Коновалова: обзор литературы и случай из практики / Ф. А. Юсупов, А. А. Юлдашев // Бюллетень науки и практики. – 2023. – Т. 9, № 3. – С. 194-210. – Yusupov, F.A. Wilson-Konovalov disease: case practices do not decrease literature review / F. A. Yusupov, A. A. Yuldashev // Bulletin of the Practice of Science of the Year. – 2023. – Vol. 9, No. 3. – pp. 194-210. – doi: 10.33619/2414-2948/88/22. – EDN PSTZYU.
  14. Engel B, Diestelhorst J, Hupa-Breier KL, Kirchner T, Henjes N, Loges S, Yuksel M, Janczyk W, Lalanne C, Zachou K, Oo YH, Gournay J, Pape S, Drenth JPH, Renand A, Dalekos GN, Muratori L, Socha P, Ma Y, Arikan C, Baumann U, Manns MP, Wedemeyer H, Junge N, Jaeckel E, Taubert R. Detection of polyreactive immunoglobulin G facilitates diagnosis in children with autoimmune hepatitis. Hepatol Int. 2024 Aug;18(4):1214-1226. doi: 10.1007/s12072-024-10695-1.
  15. Gromadzka G, Czerwińska J, Krzemińska E, Przybyłkowski A, Litwin T. Wilson's Disease-Crossroads of Genetics, Inflammation and Immunity/Autoimmunity: Clinical and Molecular Issues. Int J Mol Sci. 2024 Aug 20;25(16):9034. doi: 10.3390/ijms25169034.
  16. Klotz W, Herold M. How to test antinuclear antibodies to diagnose autoimmune hepatitis. J Hepatol. 2023 Nov; 79(5):e206-e207. https://doi.org/10.1016/j.jhep.2023.07.006

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) Zhuzhula A.A., Kurbatova O.V., Petrichuk S.V., Fisenko A.P., Snovskaya M.A., Movsisyan G.B., Potapov A.S., Semikina E.L.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № 77 - 11525 от 04.01.2002.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies