Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 132-139
Клинический случай интерферонопатии 1-го типа: гомозиготная мутация в гене STAT2 c усилением активности белка
https://doi.org/10.24287/1726-1708-2021-20-3-132-139Аннотация
Статья посвящена крайне редкому варианту интерферонопатии 1-го типа, связанному с гомозиготной мутацией с усилением активности белка gain of function (GOF) в гене STAT2 у ребенка 5 лет. Впервые данный генетический вариант был описан в 2019 г. и к настоящему времени известно всего 3 случая с подобной патологией. В статье представлен четвертый клинический случай и наш опыт ведения пациента с STAT2 GOF, также приведены ключевые аспекты патогенеза, клинической картины на основании анализа известных случаев этого заболевания. Отсутствие установленных критериев и методов лечения данного заболевания обусловлено редкостью встречаемости и относительной новизной описанной нозологии. Нами представлен опыт лечения с использованием ингибитора JAK-киназы с последующей оценкой эффективности проводимой терапии и нежелательных явлений. Родители пациентки дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.
Список литературы
1. Клинические рекомендации Министерства здравоохранения Российской Федерации. Интерферонопатии I типа. 2018.
2. Duncan C.J.A., Thompson B., Chen R., Rice G.I., Gothe F., Young D.F., et al. Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2. Sci Immunol 2019; 4 (42): eaav7501. DOI: 10.1126/sciimmunol.aav7501
3. Gruber C., Martin-Fernandez M., Ailal F., Qiu X., Taft J., Altman J., et al. Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy. J Exp Med 2020; 217 (5): e20192319. DOI: 10.1084/jem.20192319
4. Uddin S., Chamdin A., Platanias L.C. Interaction of the transcriptional activator Stat-2 with the type I interferon receptor. J Biol Chem 1995; 270 (42): 24627–30. DOI: 10.1074/jbc.270.42.24627
5. MacLennan I., Vinuesa C. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses. Immunity 2002; 17 (3): 235–8. DOI: 10.1016/s1074-7613(02)00398-9
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7. Basters A., Knobeloch K.-P., Fritz G. USP18 – a multifunctional component in the interferon response. Biosci Rep 2018; 38 (6): BSR20180250. DOI: 10.1042/BSR20180250
8. Arimoto K.-I., Löchte S., Stoner S.A., Burkart C., Zhang Y., Miyauchi S., et al. STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling. Nat Struct Mol Biol 2017; 24 (3): 279–89. DOI: 10.1038/nsmb.3378
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11. Arjunaraja S., Snow A.L. Gain-offunction mutations and immunodeficiency: at a loss for proper tuning of lymphocyte signaling. Curr Opin Allergy Clin Immunol 2015; 15 (6): 533–8.
12. Hambleton S., Goodbourn S., Young D.F., Dickinson P., Mohamad S.M., Valappil M., et al. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci U S A 2013; 110 (8): 3053–8.
Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 132-139
Clinical case of type I interferonopathy: homozygous STAT2 gain-of-function mutation
https://doi.org/10.24287/1726-1708-2021-20-3-132-139Abstract
The article is devoted to an extremely rare variant of type I interferonopathies associated with a homozygous gain of function (GOF) mutation in the STAT2 gene in a 5-year-old child. This genetic defect was first described in 2019, and so far only 3 cases are known in the world with a similar pathology. Here we present the fourth clinical case and our experience in managing a patient with STAT2 GOF. The article presents the key aspects of the pathogenesis, clinical picture based on the analysis of all known cases of the disease. The absence of established criteria and methods of treatment for this disease is due to the rarity and relative novelty of the described nosology. We present the experience of treatment using a JAK kinase inhibitor, followed by an assessment of the effectiveness of the therapy and side effects. The patient's parents agreed to use the information, including the child's photo, in scientific research and publications.
References
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2. Duncan C.J.A., Thompson B., Chen R., Rice G.I., Gothe F., Young D.F., et al. Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2. Sci Immunol 2019; 4 (42): eaav7501. DOI: 10.1126/sciimmunol.aav7501
3. Gruber C., Martin-Fernandez M., Ailal F., Qiu X., Taft J., Altman J., et al. Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a patient with type I interferonopathy. J Exp Med 2020; 217 (5): e20192319. DOI: 10.1084/jem.20192319
4. Uddin S., Chamdin A., Platanias L.C. Interaction of the transcriptional activator Stat-2 with the type I interferon receptor. J Biol Chem 1995; 270 (42): 24627–30. DOI: 10.1074/jbc.270.42.24627
5. MacLennan I., Vinuesa C. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses. Immunity 2002; 17 (3): 235–8. DOI: 10.1016/s1074-7613(02)00398-9
6. d'Angelo D.M., Di Filippo P., Breda L., Chiarelli F. Type I Interferonopathies in Children: An Overview. Front Pediatr 2021; 9: 631329. DOI: 10.3389/fped.2021.631329
7. Basters A., Knobeloch K.-P., Fritz G. USP18 – a multifunctional component in the interferon response. Biosci Rep 2018; 38 (6): BSR20180250. DOI: 10.1042/BSR20180250
8. Arimoto K.-I., Löchte S., Stoner S.A., Burkart C., Zhang Y., Miyauchi S., et al. STAT2 is an essential adaptor in USP18-mediated suppression of type I interferon signaling. Nat Struct Mol Biol 2017; 24 (3): 279–89. DOI: 10.1038/nsmb.3378
9. Kozlova A.L., Romanenko E.S., Burlakov V.I., Deripapa E.V., Khomyakova S.P., Remizov A.N. i dr. Klinicheskii sluchai interferonopatii I tipa: sindrom Aikardi–Gut'eres. Pediatriya 2019; 98 (3): 257–65. DOI: 10.24110/0031-403X-2019-98-3-257-265
10. Bousfiha A., Jeddane L., Picard C., Al-Herz W., Ailal F., Chatila T., et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 2020; 40 (1): 66–81.
11. Arjunaraja S., Snow A.L. Gain-offunction mutations and immunodeficiency: at a loss for proper tuning of lymphocyte signaling. Curr Opin Allergy Clin Immunol 2015; 15 (6): 533–8.
12. Hambleton S., Goodbourn S., Young D.F., Dickinson P., Mohamad S.M., Valappil M., et al. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci U S A 2013; 110 (8): 3053–8.
