Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children35610.24287/1726-1708-2020-19-2-193-199LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫEculizumab in the treatment of complement system disorders including paroxysmal nocturnal hemoglobinuriaЭкулизумаб в терапии патологии системы комплемента при пароксизмальной ночной гемоглобинурииhttps://orcid.org/0000-0002-3297-1608BakirovB. A.БакировБ. А.
Russian Federation

Dr. of Sci. (Med.), Associate Professor, Head of Department of Hospital Therapy №2,

Russia, 450075, Ufa, Blukhera st., 3

д-р мед. наук, доцент, заведующий кафедрой госпитальной терапии №2,

450075, Уфа, ул. Блюхера, 3

bakirovb@gmail.comhttps://orcid.org/0000-0003-1878-4467KudlayD. A.КудлайД. А.
Russian Federation
https://orcid.org/0000-0003-2125-4897PavlovV. N.ПавловВ. Н.
Russian Federation
Bashkir State Medical University of the Ministry of Healthcare of the Russian FederationФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава РоссииАО “GENERIUM”АО «ГЕНЕРИУМ»NRC “Institute of Immunology” of the FMBA of RussiaФГБУ «Государственный научный центр «Институт иммунологии» ФМБА России020720201921931990207202002072020Copyright ©; 2020, «D. Rogachev NMRCPHOI»Copyright ©; 2020, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2020«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/356

The main function of the complement system is to provide humoral defence against foreign pathogens. It contributes to immune response and is a crucial component of innate immunity that provides immediate non-specific immune defence. Inherited or acquired deficiencies of the complement system associated with excessive activation or other impairments of complement activity have varied clinical manifestations. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal blood disorder that clinically manifests with anemia, thrombosis, chest and abdominal pain, chronic kidney disease and bone marrow failure. The complement-mediated hemolysis due to the lack of membrane-bound complement-regulatory proteins CD55 and CD59 is a central underlying mechanism of the disease and mortality associated with PNH. The severity of clinical symptoms determines the type of treatment which may include allogeneic hematopoietic stem cell transplantation and pathogenetic treatment through the inhibition of the complement system. Eculizumab, a humanized monoclonal anti-C5 antibody, has become the first complement inhibitor to show effectiveness in treating any of complement-mediated hemolytic anemias and now serves as a standard of treatment for patients with PNH. Brisk development of biotechnological methods for the production of new drugs in Russia has enabled the initiation of drug discovery efforts and the creation of the world's first biosimilar of Eculizumab.

Основной функцией системы комплемента является гуморальная защита организма от действия чужеродных микроорганизмов. Она участвует в реализации иммунного ответа и является важным компонентом врожденного иммунитета, обеспечивающего быструю неспецифическую иммунологическую защиту организма. Врожденные или приобретенные недостатки системы комплемента, сопровождающиеся избыточной активацией или другими нарушениями ее активности, имеют широкий спектр клинических проявлений. Пароксизмальная ночная гемоглобинурия (ПНГ) является редким приобретенным клональным заболеванием крови, клинически проявляющимся анемией, тромбозами, болями в груди и животе, хронической болезнью почек и недостаточностью костного мозга. Комплемент-опосредованный гемолиз вследствие отсутствия связанных с мембраной белков ингибиторов мембранного комплемента CD55 и CD59 является центральным механизмом, лежащим в основе заболевания и летальности, связанной с ПНГ. Тяжесть клинических симптомов определяет лечение, которое включает аллогенную трансплантацию гемопоэтических стволовых клеток и патогенетическую терапию посредством ингибирования системы комплемента. Гуманизированное моноклональное анти-С5-антитело экулизумаб стало первым ингибитором комплемента, показавшего эффективность при любой опосредованной им гемолитической анемии, и сегодня является стандартом терапии для пациентов с ПНГ. Активное развитие биотехнологических методов получения новых лекарственных препаратов в России позволило начать разработку и создать первый в мире биоаналогичный препарат экулизумаба.

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