Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press1699310.36691/RJA16993Case reportsКлинические случаиResearch ArticleRecurrent angioedema with normal C1-inhibitor: genetics determine the endotypeРецидивирующие ангиоотеки с нормальным уровнем С1-ингибитора: генетическое обследование определяет эндотипhttps://orcid.org/0000-0002-9545-47201857-8154LebedkinaMarina S.ЛебедкинаМарина Сергеевна
Russian Federation

MD

marina.ivanova0808@yandex.ruhttps://orcid.org/0000-0002-5083-66373023-4538FominaDarya S.ФоминаДарья Сергеевна
Russian Federation

MD, Cand. Sci. (Med.), Assistant Professor

канд. мед. наук, доцент

daria_fomina@mail.ruhttps://orcid.org/0000-0002-6534-59025806-7260BobrikovaElena N.БобриковаЕлена Николаевна
Russian Federation

MD

elena.bobrikova.69@mail.ruhttps://orcid.org/0000-0002-0928-20541688-2416YukhnovskayaYulia D.ЮхновскаяЮлия Дмитриевна
Russian Federation
yukhyuliya@yandex.ruhttps://orcid.org/0000-0001-5132-12677249-4423RoppeltAnna A.РоппельтАнна Артуровна
Russian Federation

MD, Cand. Sci. (Medicine)

канд. мед. наук

roppelt_anna@mail.ruhttps://orcid.org/0000-0002-4949-91782884-5000KruglovaTatyana S.КругловаТатьяна Сергеевна
Russian Federation

MD, Cand. Sci. (Medicine)

канд. мед. наук

surckova.t@yandex.ruhttps://orcid.org/0000-0002-3794-49917721-1941MukhinaOlga A.МухинаОльга Алексеевна
Russian Federation
mukhina.o.a@gmail.comhttps://orcid.org/0000-0002-6646-42336424-0012MаrkinaUlyana A.МаркинаУльяна Алексеевна
Russian Federation
itcher.md@bk.ruhttps://orcid.org/0000-0002-0865-83553507-9106NikitinaEkaterina A.НикитинаЕкатерина Андреевна
Russian Federation
katrin88866@gmail.comhttps://orcid.org/0000-0002-4131-24365379-3655AlekseevaYulia G.АлексееваЮлия Геннадьевна
Russian Federation
doctorajg5@gmail.comhttps://orcid.org/0000-0002-1930-54244122-5565KaraulovAleksandr V.КарауловАлександр Викторович
Russian Federation

MD, Dr. Sci. (Medicine), Professor

д-р мед. наук, профессор

drkaraulov@mail.ruhttps://orcid.org/0000-0001-6010-79753887-6250LysenkoMariana A.ЛысенкоМарьяна Анатольевна
Russian Federation

MD, Dr. Sci. (Medicine), Professor

д-р мед. наук, профессор

gkb52@zdrav.mos.ruMoscow City Hospital 52Городская клиническая больница № 52, МоскваThe First Sechenov Moscow State Medical University (Sechenov University)Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)Astana Medical UniversityМедицинский университет АстанаLife Improvement by Future Technologies (LIFT) Center«ЛИФТ Центр»The Russian National Research Medical University named after N.I. PirogovРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова030320251004202522167852001202525022025Copyright ©; 2025, PH “ABV-Press”Copyright ©; 2025, ООО «ИД «АБВ-пресс»2025PH “ABV-Press”ООО «ИД «АБВ-пресс»https://rusalljournal.ru/raj/article/view/16993

Hereditary angioedema with normal C1 esterase inhibitor is a rare genetic disorder characterized by periodical and unpredictable angioedema without quantitative and qualitative deficiency of C1-inhibitor. According to the modern classification, this disease can present as two different endotypes: bradykinin-mediated and endothelium dysfunction-associated. Diagnosis of this disease is complicated by the need to perform genetic screening because available laboratory tests (C1-inhibitor, its functionality, and C4 protein in blood plasma) are within normal values, functional molecular tests are not available, clinical data are limited to few cohorts and, for some genetic defects, to single clinical observations. Genetic examination of patients with recurrent angioedema expands the cohort of patients with hereditary angioedema and normal C1 esterase inhibitor.

The article describes 17 patients with hereditary angioedema with normal C1 esterase inhibitor who underwent treatment at a specialized center in Moscow. The bradykinin-mediated angioedema endotype was found in 13 patients (9 with mutation in PLG, 2 with mutation in FXII, and 2 with mutation in KNG1), and endothelium dysfunction-associated angioedema was diagnosed in 4 patients with mutation in MYOF (2 asymptomatic carriers). Currently, data on the clinical presentation, diagnosis, and therapy of patients are limited to single clinical cases and small clinical case series, thus further data collection is needed.

The publication contains unique data on the algorithm of diagnosis and selection of therapy in patients with angioedema and normal C1-inhibitor level.

Форма наследственного ангиоотека с нормальным уровнем ингибитора С1-эстеразы — орфанное генетическое заболевание, характеризующееся периодически возникающими эпизодами ангиоотеков без количественного и качественного дефицита С1-ингибитора. Согласно современной классификации данное заболевание может быть представлено 2 различными эндотипами: брадикинин-опосредованным и ассоциированным с дисфункцией эндотелия сосудов. Диагностика заболевания осложняется необходимостью проведения генетического скрининга, поскольку результаты доступных лабораторных тестов (уровень С1-ингибитора, его функциональная активность и уровень С4-компонента комплемента) находятся в пределах нормальных значений, функциональные молекулярные тесты недоступны, клинические данные ограничены немногочисленными когортами, а для некоторых генетических дефектов — единичными клиническими наблюдениями.

Описана история лечения 17 пациентов с наследственным ангиоотеком с нормальным уровнем C1-ингибитора, наблюдающихся в профильном центре города Москвы. К эндотипу брадикинин-опосредованного ангиоотека относятся 13 пациентов (9 — с мутацией в гене PLG, 2 — в гене FXII, 2 — в гене KNG1), к эндотипу, ассоциированому с дисфункцией эндотелия сосудов, — 4 пациента с мутацией в гене MYOF (из них 2 бессимптомных носителя). Данные о клинической картине, диагностике и терапии пациентов ограничены, сбор и анализ по указанным вариантам рецидивирующих ангиоотеков — приоритетная проблема современной аллергологии.

Представлены уникальные материалы по алгоритму диагностики и подбору терапии для пациентов с наследственным ангиоотеком с нормальным уровнем C1-ингибитора.

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