vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v14i3.1372vsp-700Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКлинические и молекулярно- генетические особенности аутовоспалительных синдромов у детейClinical and Molecular Genetic Features of Autoinflammatory Syndromes in ChildrenАлексееваЕ. И.AlexeevaЕ. I.

доктор медицинских наук, профессор, заведующая ревматологическим отделением Научного центра здоровья детей, декан педиатрического факультета Первого МГМУ им. И.М. Сеченова

alekatya@yandex.ruСавостьяновК. В.SavostyanovK. V.СлепцоваТ. В.SleptsovaТ. V.ПушковА. А.PushkovА. А.ВалиеваС. И.ValievaS. I.БзароваТ. М.BzarovaТ. М.ИсаеваК. Б.IsaevaK. B.ЧистяковаЕ. Г.ChistyakovaЕ. G.ЧомахидзеА. М.ChomakhidzeА. М.ДенисоваР. В.DenisovaR. V.НикитинА. Г.NikitinА. G.ПахомовА. В.PakhomovА. V.Научный центр здоровья детей, Москва, Российская Федерация Первый Московский государственный медицинский университет им. И.М. Сеченова, Российская ФедерацияРоссияScientific Centre of Children Health, Moscow, Russian Federation I.M. Sechenov First Moscow State Medical University, Russian FederationRussian FederationНаучный центр здоровья детей, Москва, Российская ФедерацияРоссияScientific Centre of Children Health, Moscow, Russian FederationRussian Federation201525082015143Вопросы современной педиатрии363373Copyright © Алексеева Е.И., Савостьянов К.В., Слепцова Т.В., Пушков А.А., Валиева С.И., Бзарова Т.М., Исаева К.Б., Чистякова Е.Г., Чомахидзе А.М., Денисова Р.В., Никитин А.Г., Пахомов А.В., 20152015Алексеева Е.И., Савостьянов К.В., Слепцова Т.В., Пушков А.А., Валиева С.И., Бзарова Т.М., Исаева К.Б., Чистякова Е.Г., Чомахидзе А.М., Денисова Р.В., Никитин А.Г., Пахомов А.В.Alexeeva Е.I., Savostyanov K.V., Sleptsova Т.V., Pushkov А.А., Valieva S.I., Bzarova Т.М., Isaeva K.B., Chistyakova Е.G., Chomakhidze А.М., Denisova R.V., Nikitin А.G., Pakhomov А.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/700

Цель исследования: изучить распространенность и особенности клинической картины аутовоспалительных синдромов среди больных системным ювенильным идиопатическим артритом. Методы: проведено проспективное нерандомизированное исследование. У всех его участников методом секвенирования изучали наличие мутаций в генах TNFRSF1A и NLRP3. Результаты: обследованы 90 детей (27 мальчиков, 63 девочки) в возрасте от 1 до 17 (медиана 8,2) лет с направляющим диагнозом: «Системный ювенильный идиопатический артрит». В результате у 10 (14%) пациентов обнаружены мутации в гене TNFRSF1A, приводящие к развитию TRAPS-синдрома (у 8 — наиболее распространенная мутация R92Q; у 3 — не описанные ранее мутации в гене NLRP3). У 2 пациентов был диагностирован синдром CINCA/NOMID, у 1 — синдром Макла–Уэллса. В 3 случаях у родственников первой линии родства были идентифицированы мутации, приводящие к развитию TRAPS-синдрома. Рассмотрены классические примеры аутовоспалительных синдромов, таких как криопиринассоциированный периодический синдром (CAPS) и периодический синдром, ассоциированный с рецептором фактора некроза опухоли (TRAPS). Представлены данные об их патогенезе, клинических признаках, диагностике и лечении. Заключение: показано, что своевременное выявление и адекватное лечение пациентов с аутовоспалительными синдромами, характеризующимися тяжелым течением и серьезным прогнозом, затруднено по причинам недостаточной осведомленности врачей-педиатров и недоступности генетической диагностики этих синдромов. Обоснована необходимость разработки универсальной модели диагностического алгоритма выявления аутовоспалительных синдромов с применением технологии секвенирования нового поколения. 

Objective: Our aim was to study the prevalence and clinical features of autoinflammatory syndromes among patients with systemic juvenile idiopathic arthritis. Methods: A prospective nonrandomized study was conducted. All its members have been studied for mutations in TNFRSF1A and NLRP3 genes by the sequencing method. Results: 90 children (27 boys, 63 girls) aged from 1 to 17 (average age 8.2) years, with a guide diagnosis: «Systemic juvenile idiopathic arthritis», were examined. As a result, 10 (14%) patients showed mutations in TNFRSF1A gene, leading to the development of TRAPS-syndrome (8 had the most common mutation of R92Q; 3 — not previously described mutations in NLRP3 gene). 2 patients had the diagnosis of CINCA/NOMID Syndrome, 1 — Muckle–Wells Syndrome. In three cases, mutations leading to the development of TRAPS-syndromethe were identified in the first line of descent. Classical examples of autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS), and tumor necrosis factor receptor associated periodic syndrome (TRAPS). The data about their pathogenesis, clinical features, diagnosis and treatment is presented. Conclusion: It is shown that early detection and adequate treatment of patients with autoinflammatory syndromes, characterized by severe disease and serious prognosis, is difficult due to lack of awareness of pediatricians and unavailability of genetic diagnosis of these syndromes. The necessity of the development of a universal model of the diagnostic algorithm for identification of autoinflammatory syndromes using next-generation sequencing technologies is grounded. 

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The authors declare that there are no conflicts of interest present.