mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-DHM-2396mimmun-2396Research ArticleОБЗОРЫREVIEWSЛекарственная гиперчувствительность. Механизмы формирования и возможности лабораторной диагностикиDrug hypersensitivity: Mechanisms and opportunities of laboratory diagnosticshttps://orcid.org/0000-0002-6907-2817БычковаН. В.BychkovaN. V.

Бычкова Наталия Владимировна – кандидат биологических наук , старший научный сотрудник лаборатории клинической иммунологии ФГБУ «Всероссийский центр экстренной и радиационной медицины имени А.М. Никифорова» Министерства РФ по делам гражданской обороны, чрезвычайным ситуациям и ликвидации последствий стихийных бедствий; доцент кафедры иммунологии ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ

198216, Санкт-Петербург, Ленинский пр., 129, корп. 5, кв. 66

Bychkova Nataliya V. , PhD (Biology), Senior Research Associate, Laboratory of Clinical Immunology, A. Nikiforov Russian Centre of Emergency and Radiation Medicine; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov Medical University

198216, St. Petersburg, Leninsky ave., 129, bldg 5, apt 66

bnv19692007@yandex.ruФГБУ «Всероссийский центр экстренной и радиационной медицины имени А.М. Никифорова» Министерства РФ по делам гражданской обороны, чрезвычайным ситуациям и ликвидации последствий стихийных бедствий; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияA. Nikiforov Russian Centre of Emergency and Radiation Medicine; First St. Petersburg State I. Pavlov Medical UniversityRussian Federation202220042022242235246Copyright © Бычкова Н.В., 20222022Бычкова Н.В.Bychkova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2396

Постоянный рост частоты встречаемости реакций гиперчувствительности на лекарственные препараты наблюдается во всем мире и вызывает тревогу у врачей всех специальностей. Проблемы диагностики, профилактики и лечения реакций гиперчувствительности обусловлены тем, что, с одной стороны, схожие клинические проявления могут иметь в основе различные патогенетические механизмы, а с другой стороны, клинические симптомы, ответ на терапию и исход заболевания значительно зависят от особенностей состояния пациента. Выделены фенотипы (определяемые клиническими проявлениями) и эндотипы (обусловленные механизмами формирования) реакций гиперчувствительности для персонификации терапии. Охарактеризованы два фенотипа – с немедленным (1-6 часов) и замедленным (более 6 часов) началом заболевания. Среди эндотипов рассматриваются 4 типа гиперчувствительности по Gell и Coombs с наличием первичной сенсибилизации. Помимо этого, выделяют взаимодействие лекарств с иммунными рецепторами на лимфоцитах, согласно фармаколого-иммунной концепции Pichler, и влияние лекарственных средств напрямую на рецепторы эффекторных клеток и сигнальные каскады без первичной сенсибилизации и очень быстро, что ранее классифицировалось как «псевдоаллергия». Для оптимизации терапии и предупреждения повторных реакций пациентам с лекарственной гиперчувствительностью необходима качественная диагностика с установлением причинно-значимого аллергена. В настоящее время она включает анамнестические данные, физикальный осмотр, тесты in vivo и in vitro. Провокационное тестирование из-за значительного риска выраженных побочных реакций применяется редко. Кожные тесты являются надежным и экономичным инструментом в том случае, если анамнез указывает на возможность IgE-зависимых реакций. Среди неспецифических методов лабораторной диагностики наибольшее клиническое значение показано для определения уровня триптазы в сыворотке крови, особенно при анафилактических реакциях. Среди специфических лабораторных методов, помимо генетического тестирования, используется измерение уровня специфических IgE к лекарствам, оценка активации и пролиферации лимфоцитов на антиген, а также тест активации базофилов, который обладает рядом преимуществ и позволяет выявить причинно-значимый аллерген для реакций гиперчувствительности, обусловленных различными механизмами. Поскольку ключевым фактором в развитии аллергического воспаления является нарушение процессов регуляции, то понимание механизмов нормализации нарушенной регуляторной функции иммунной системы откроет новые стратегии персонифицированного лечения, направленные в том числе и на модулирование функций регуляторных клеток для достижения контроля над реакциями лекарственной гиперчувствительности.

Permanently increased frequency of drug hypersensitivity is observed throughout the world and continues to be of concern to clinicians of either discipline. Diagnostic problems with prevention and treatment of hypersensitivity reactions are due to different pathogenetic mechanisms that may underly similar clinical manifestations. On the other hand, clinical symptoms, response to therapy and the outcome of the disease significantly depend on clinical state of the patient. The phenotypes which are determined by clinical manifestations, and endotypes dependent on the pathogenetic mechanisms of hypersensitivity reactions were specified to the purpose of personalized therapy. Two kinds of phenotypes are described: with immediate (1-6 hours) and delayed (more than 6 hours) onset of the response. Four types of hypersensitivity according to Gell and Coombs with the presence of primary sensitization are discerned between the endotypes. Moreover, interaction of drugs with immune receptors of lymphocytes, according to the Pichler’s pharmaco-immune concept, has been identified, along with quick impact of drugs directly upon receptors of effector cells and signaling cascades without primary sensitization, which was previously termed as “pseudo-allergy”. To optimize therapy and prevent repeated reactions in the patients with drug hypersensitivity, high-quality diagnostics with detection of the causal allergen is required. This strategy currently includes analysis of medical history, physical examination as well as in vivo and in vitro testing. Provocation tests are rarely used, due to the significant risk of severe adverse reactions. Skin tests are a reliable and cost-effective tool, if the case history infers possibility of IgE-dependent reactions. Among nonspecific laboratory markers, the greatest clinical value is shown for determining serum tryptase levels, especially in anaphylactic reactions. In addition to genetic testing, several specific laboratory methods are used, i.e., measuring levels of drug-specific IgE, assessment of antigen-induced activation and proliferation of lymphocytes as well as basophil activation test, which has a number of advantages and allows us to identify a causally significant allergen for the hypersensitivity reactions proceeding by various mechanisms. Due to dysregulation which is a key factor of allergic inflammation, the mechanisms of normalization for impaired immune regulation should be understood, thus offering new strategies for personalized treatment, e.c., modulating the regulatory cell functions, aiming for control of the drug hypersensitivity reactions.

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