nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/2618-9801-2023-3-345-359nid-119Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESС3 гломерулопатия: путь от световой микроскопии до таргетной терапииC3 glomerulopathy: a long way from the light microscopy findings to the targeted therapyЗахароваЕ.В.ZakharovaE. V.helena.zakharova@gmail.comЗыковаА. С.ZykovaA. S.ansezy@gmail.comГБУЗ “Городская клиническая больница имени С.П. Боткина” Департамента здравоохранения города Москвы; ФГБОУ ДПО “Российская медицинская академия непрерывного профессионального образования” Министерства здравоохранения Российской Федерации; ФДПО ФГБОУ ВО «Московский государственный медико-стоматологический университет имени А.И. Евдокимова» Министерства здравоохранения Российской ФедерацииРоссияS.P. Botkin City Clinical Hospital of Moscow City Healthcare Department; Russian Medical Academy of Continuing Professional Education of Russian Federation Ministry of Health; A.I. Evdokimov Moscow State University of Medicine and Dentistry of Russian Federation Ministry of HealthRussian FederationГБУЗ “Городская клиническая больница имени С.П. Боткина” Департамента здравоохранения города Москвы; ФФМ ФГБОУ ВО «Московский Государственный Университет имени М.В. Ломоносова»РоссияS.P. Botkin City Clinical Hospital of Moscow City Healthcare Department; M.V. Lomonosov Moscow State UniversityRussian Federation202321062024253345359Copyright © Захарова Е.V., Зыкова А.С., 20242024Захарова Е., Зыкова А.С.Zakharova E.V., Zykova A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/119

C3 гломерулопатия - ультра-редкое заболевание, обусловленное дисрегуляцией каскада альтернативного пути комплемента и отложением депозитов С3 в клубочках. История изучения состояний, объединяемых в настоящее время под термином С3 гломерулопатия (С3 ГП), охватывает более чем 60-летний период времени и характеризуется значительным изменением представлений о патоморфологии и патогенезе заболевания. В основе патогенеза лежат либо (чаще) приобретенные факторы - антитела к конвертазам альтернативного пути, либо (реже) генетические факторы - мутации генов, кодирующих регуляторы альтернативного пути активации комплемента; триггерными механизмами служат аутоиммунные заболевания, инфекции и моноклональные гаммапатии. Клиническое течение С3 ГП варьирует от изолированного мочевого синдрома до быстропрогрессирующего гломерулонефрита. Снижение уровня С3 компонента комплемента в сыворотке, являющееся важным биомаркером активации альтернативного пути комплемента, обнаруживается не во всех случаях. Однако его отсутствие не опровергает диагноз С3 ГП. Ключевым для диагностики является иммуноморфологическое исследование биоптата почечной ткани, демонстрирующее изолированное или доминантное свечение С3 компонента комплемента, при этом световая микроскопия чаще всего, но не всегда, обнаруживает мембранопролиферативный профиль повреждения. Клиническое течение и ответ на терапию определяют такие факторы как генетическая предрасположенность, возраст дебюта, присутствие специфических аутоантител или моноклонального иммуноглобулина. Генетические методы исследования играют важную, но вспомогательную роль в диагностике отдельных вариантов С3 ГП, выявление генетических мутаций позволяет прогнозировать ответ на иммуносупрессивную терапию и особенно значимо при обследовании реципиентов и потенциальных родственных доноров перед трансплантацией почки. Ответ на рекомендуемую в настоящее время при средне-тяжелом и тяжелом течении С3 ГП терапию глюкокориткоидами и микофенолатами отмечается не у всех пациентов, однако появление новых молекул, воздействующих на каскад альтернативного пути активации комплемента, также как и клон-ориентированные методы лечения, создают перспективы для таргетной и индивидуализированной терапии, эффективность которой только предстоит оценить.

C3 glomerulopathy is an ultra-rare disease, driven by alternative complement pathway dysregulation, which results in C3 deposition in glomeruli. History of studying the conditions, currently merged under the umbrella of C3 glomerulopathy (С3 GP), counts more than 60 years of capturing substantial changes in the understanding of both pathology and pathogenesis of these diseases. The main pathogenetic factors are either (more commonly) acquired - antibodies against alternative pathway convertases, or (less commonly) genetic - mutations of genes, encoding alternative pathway regulators. The disease phenotype is triggered by autoimmune conditions, infections, or monoclonal gammopathy. The clinical course of C3 GP varies from mild proteinuria and hematuria to rapidly progressive glomerulonephritis syndrome. The decrease of serum C3 levels serving as an important biomarker of the alternative pathway activation is not always detectable; however, normal C3 levels do not rule out C3 GP diagnosis. The key diagnostics tool is immunostaining, demonstrating isolated or dominant C3 expression, while light microscopy commonly, but not exclusively, shows a membranoproliferative pattern of injury. Clinical course and response to the immunosuppressive treatment depend on such factors as genetic predisposition, age of the disease onset, and presence of specific autoantibodies or monoclonal immunoglobulins. Genetic investigations play an important auxiliary role in the diagnostics of genetic forms of C3 GP, genetic abnormalities are important predictors of the response to immunosuppressive treatmentи and they are key determinates for the evaluation of recipients and potential relative donors for kidney transplantation. Response to the currently recommended treatment of the moderate-to-severe C3 GP with glucocorticosteroids and mycophenolates is not universal, however, emerging new molecules against complement cascade factors, as well as clone-oriented treatment, open perspectives for the targeted individualized therapy, which efficacy remains to be further studied and evaluated.

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