Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children103910.24287/j.1039ZSLPFCORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИResearch ArticleFeatures of diagnosis and management of patients with autoimmune lymphoproliferative syndrome caused by somatic defects of the FAS geneОсобенности диагностики и ведения пациентов с аутоиммунным лимфопролиферативным синдромом вследствие соматических дефектов гена FAShttps://orcid.org/0000-0001-5347-7150ShvetsOksana A.ШвецОксана Анатольевна
Russian Federation

Cand. Med. Sci., Associate Professor of the Department of Allergology and Immunology, an allergist/immunologist at the Outpatient Clinic

канд. мед. наук, доцент кафедры аллергологии-иммунологии, врач-аллерголог-иммунолог консультативного отделения

shv1808@rambler.ruhttps://orcid.org/0000-0003-2467-2840KievaA. M.КиеваА. М.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-7082-1694SemchenkovaA. A.СемченковаА. А.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0003-4427-054XNesterenkoZ. A.НестеренкоЗ. А.
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shv1808@rambler.ruhttps://orcid.org/0000-0003-3564-6496KanN. Yu.КанН. Ю.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-6134-3811MoiseevaA. A.МоисееваА. А.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0003-2897-5208BogdanovaD. V.БогдановаД. В.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-8208-2075DeordievaE. A.ДеордиеваЕ. А.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0003-1267-9957BurlakovV. I.БурлаковВ. И.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0001-8586-8586KuzminovaZh. A.КузьминоваЖ. А.
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shv1808@rambler.ruhttps://orcid.org/0000-0002-6553-2505FadeevaM. S.ФадееваМ. С.
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shv1808@rambler.ruhttps://orcid.org/0000-0002-6148-7209PershinD. E.ПершинД. Е.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0003-3664-2876AbramovD. S.АбрамовД. С.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-1014-5196MannS. G.МаннС. Г.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-2521-5353AleksenkoM. Yu.АлексенкоМ. Ю.
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shv1808@rambler.ruhttps://orcid.org/0000-0003-0471-2956MersiyanovaI. V.МерсияноваИ. В.
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shv1808@rambler.ruhttps://orcid.org/0000-0003-0900-6874KurnikovaM. A.КурниковаМ. А.
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shv1808@rambler.ruhttps://orcid.org/0000-0002-8805-1499SmetaninaN. S.СметанинаН. С.
Russian Federation
shv1808@rambler.ruhttps://orcid.org/0000-0002-3113-4939ShcherbinaA. Yu.ЩербинаА. Ю.
Russian Federation
shv1808@rambler.ruThe Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России2901202624415300810202505112025Copyright ©; 2026, «D. Rogachev NMRCPHOI»Copyright ©; 2026, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2026«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/1039

Introduction. Autoimmune lymphoproliferative syndrome (ALPS) is an inborn error of immunity with impaired FAS-mediated apoptosis. The disease responds well to therapy with the mTORC1-inhibitor sirolimus (SRL). The diagnosis of ALPS is based on the European Society for Immunodeficiencies (ESID) diagnostic criteria, which include the main clinical manifestations in combination mainly with an increased level of double-negative T-lymphocytes (DNT) with the CD3+TCRαβ+CD4–CD8–-phenotype. Most cases of ALPS are caused by germinal mutations in the FAS gene, however, somatic changes in this gene (ALPS-sFAS) can be detected in 15–20% of patients.

Aim: to analyze the diagnostic features and clinical presentation before and during SRL treatment in patients with ALPS-sFAS.

Materials and methods. In our cohort of patients (n = 6), we analyzed main clinical data (clinical presentation, laboratory and instrumental data), the stages of genetic search and response to SRL therapy. We observed an early onset of the disease (median of 1.7 years), with delayed clinical (median of 3.7 years) and genetic (median of 6.2 years) diagnosis.

Results. At the initial examination, only 67% of the patients met the ESID criteria. In 50% of cases with DNT levels >9.9%, somatic mutations in the FAS gene were detected in whole blood DNA, in other cases, we analyzed DNA from sorted DNT cells. All of our patients had previously undescribed somatic mutations in the FAS gene. Our experience of SRL treatment in patients with ALPS-sFAS has been more than 10 years. We observed a good clinical response, as well as continued remission of the disease at a reduced dose of SRL (<1.5 mg/m2). In 67% of cases, various adverse events were observed when the SRL dose was >1.5 mg/m2.

Conclusion. The obtained results demonstrate the complexity of diagnosis and the need for concern regarding ALPS-cFAS, taking into account the effectiveness of pathogenetic therapy, as well as the importance of a personalized approach in molecular genetic verification of the diagnosis.

Введение. Аутоиммунный лимфопролиферативный синдром (АЛПС) является врожденным дефектом иммунитета с нарушением FAS-опосредованного апоптоза. Заболевание хорошо отвечает на терапию mTORС1-ингибитором сиролимусом (SRL). При постановке диагноза ориентируются на критерии диагностики Европейского общества иммунодефицитных состояний (European Society for Immunodeficiencies, ESID), включающие основные клинические проявления в комбинации преимущественно с повышенным содержанием дубль-негативных Т-лимфоцитов (ДНТ) с фенотипом CD3+TCRαβ+CD4–CD8–. Чаще всего в основе заболевания лежат герминальные мутации в гене FAS, однако у 15–20% пациентов могут определяться соматические изменения этого гена (АЛПС-сFAS).

Цель исследования: провести анализ особенностей диагностики, клинической картины до и на фоне лечения SRL у пациентов с АЛПС-cFAS.

Материалы и методы. Среди нашей когорты пациентов (n = 6) был проведен анализ основных клинических данных (клиническая картина, лабораторные и инструментальные данные), этапов генетического поиска и ответа на терапию SRL. Мы наблюдали ранний дебют заболевания (медиана 1,7 года) с задержкой клинической (медиана 3,7 года) и генетической (медиана 6,2 года) диагностики.

Результаты. При первичном обследовании только 67% пациентов соответствовали критериям ESID. В 50% случаев при содержании ДНТ >9,9% удалось выявить соматические мутации в гене FAS из ДНК цельной крови, в остальных случаях анализировалась ДНК, полученная из сортированных ДНТ-клеток. У всех наших пациентов были выявлены ранее не описанные соматические мутации гена FAS. Наш опыт применения SRL у пациентов с АЛПС-cFAS составил более 10 лет. Мы наблюдали хороший клинический ответ, а также сохранение ремиссии заболевания на сниженной дозе препарата (<1,5 мг/м2). В 67% случаев при приеме дозы SRL >1,5 мг/м2 наблюдались различные нежелательные явления.

Заключение. Полученные результаты демонстрируют сложность диагностики и необходимость настороженности в отношении АЛПС-сFAS с учетом эффективности патогенетической терапии, а также важность персонифицированного подхода в проведении молекулярно-генетической верификации диагноза.

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