mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2015-5-407-422mimmun-920Research ArticleОБЗОРЫREVIEWSАЛЛЕРГЕН-СПЕЦИФИЧЕСКАЯ ИММУНОТЕРАПИЯ: ТЕРАПЕВТИЧЕСКИЕ ВАКЦИНЫ ДЛЯ АЛЛЕРГИЧЕСКИХ ЗАБОЛЕВАНИЙALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASESФедоровА. С.FedorovA. S.

Врач иммунолог-аллерголог, ГБУЗ «Городская больница № 3» г. Калининграда, аспирант Балтийский федеральный университет имени И. Канта, г. Калиниград;

Адрес для переписки: Федоров Александр Станиславович Балтийский федеральный университет имени И. Канта 198260, Россия, Санкт-Петербург, ул. Стойкости, 2/11, кв. 65. Тел.: 8 (952) 057-94-65. E-mail: fedorowww@list.ru 

Physician (Allergology/ Immunology), Regional Hospital No; Research Fellow, I. Kant Baltic Federal University

fedorowww@list.ruЛитвиноваЛ. С.LitvinovaL. S.

Доктор медицинских наук, заведующая лабораторией иммунологии и клеточных биотехнологий Инновационного парка, профессор кафедры молекулярной физиологии и биофизики, Балтийский федеральный университет имени И. Канта, г. Калиниград

PhD, MD (Medicine), Head, Laboratory of Immunology and Cell Biotechnology, Innovation Park; Professor, Department of Molecular Physiology and Biophysics, I. Kant Baltic Federal University

fedorowww@list.ruБут-ГусаимВ. И.But-GusaimV. I.

Кандидат медицинских наук, врач-пульмонолог, доцент кафедры терапии медицинского института, Балтийский федеральный университет имени И. Канта, г. Калиниград

PhD (Medicine), Physician (Pulmonology), Associate Professor, Department of Therapy, Medical Institute, I. Kant Baltic Federal University

fedorowww@list.ruЛитвиненкоС. Н.LitvinenkoS. N.

Врач-пульмонолог

Physician (Pulmonology)

fedorowww@list.ruБалтийский федеральный университет имени И. Канта, КалиниградРоссияI. Kant Baltic Federal University, KaliningradRussian FederationКалининградская областная клиническая больницаРоссияKaliningrad Regional Clinical HospitalRussian Federation201507102015175407422Copyright © Федоров А.С., Литвинова Л.С., Бут-Гусаим В.И., Литвиненко С.Н., 20152015Федоров А.С., Литвинова Л.С., Бут-Гусаим В.И., Литвиненко С.Н.Fedorov A.S., Litvinova L.S., But-Gusaim V.I., Litvinenko S.N.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/920

Наиболее эффективным методом лечения аллергии является аллерген-специфическая иммунотерапия (АСИТ), которая заключается в введении малых доз антигена, ответственного за развитие состояния у конкретного пациента. При этом происходит десенсибилизация организма к этому антигену. История применения АСИТ насчитывает более 100 лет, и за это время накоплена огромная доказательная база по использованию метода в клинической практике. Применение АСИТ приводит к уменьшению симптомов и потребности в лечении и, кроме того, имеет потенциал для долгосрочного клинического эффекта, предотвращая развитие аллергии и ее симптомов. Лечение действует на основные иммунологические механизмы, ответственные за развитие клинической симптоматики. АСИТ – противовоспалительное, патогенетическое и профилактическое лечение аллергических заболеваний дыхательных путей. В обзоре проанализированы результаты важнейших клинических исследований применения АСИТ для лечения аллергических заболеваний органов дыхания (аллергический ринит и бронхиальная астма). Рассматриваются различные схемы проведения АСИТ, различные ее варианты (инъекционная и сублингвальная АСИТ), вопросы выбора препарата для АСИТ из имеющихся на сегодняшний день на фармацевтическом рынке, критерии отбора пациентов и вопросы использования современных достижений молекулярной аллергодиагностики (картирования аллергенной сенсибилизации пациента на молекулярном уровне) для их оптимизации. Рассмотрен вопрос об иммунологических механизмах АСИТ, имеющиеся сведения о которых на сегодняшний день достаточно противоречивы. Эффект АСИТ реализуется через следующие основные иммунологические механизмы: подавление увеличения концентрации эозинофилов, уменьшение продолжительности фазы замедленной гиперчувствительности, также с помощью инициации и поддержания перехода от Th2к Th1-подобному иммунологическому ответу. Регуляторные T-клетки играют основную роль в иммунологической реализации механизма АСИТ, они оказывают значительное влияние на подавление Th2-ответа. Одним из механизмов, с помощью которого это происходит, является увеличение производства специфических антител IgG, в первую очередь, подтипа IgG4. Смещение баланса между IgE и IgG4 в сторону продукции IgG4 считается на сегодняшний день принципиально важным условием для успешной АСИТ. Доказано, что аллерген-специфические IgG4 антитела против IgE сохраняются после прекращения лечения и могут обеспечить долгосрочную клиническую толерантность. Рассмотрены перспективы создание новых форм и разновидностей лекарственных препаратов для АСИТ. До клинической практики на настоящий момент дошли две группы препаратов для АСИТ: аллергены и аллергоиды (аллергены, химически модифицированные путем обработки формальдегидом с целью повышения их иммуногенности и снижения частоты побочных аллергических реакций, возникающих при их применении). Отдельно рассматриваются иммунологические механизмы СЛИТ (сублингвальной иммунотерапии). СЛИТ является на сегодняшний день наиболее безопасным и перспективным вариантом АСИТ, ее применение наиболее целесообразно в педиатрической практике.

Allergen-specific immunotherapy (ASIT) is the most effective method of allergy treatment which consists of exposure to small doses of antigen responsible for development of allergic condition in the particular patient. Therefore, one may achieve desensitization to this antigen. The history of ASIT application lasts for more than 100 years, and, over this time, huge clinical evidence for the usage of the method has been accumulated. Use of ASIT causes reduction of allergy symptoms and treatment needs and, moreover, it has the potential for long-term clinical benefit, by preventing the development of allergy and its symptoms. The treatment affects basic immunological mechanisms responsible for the development of clinical symptoms. ASIT is an antiinflammatory, pathogenetic and prophylactic treatment of allergic airway disease. The review considers the results of major clinical trials of the ASIT applications for treatment of allergic diseases of the respiratory system (allergic rhinitis and bronchial asthma). Various schemes of ASIT are discussed including its different variants (injectable and sublingual ASIT), the issues of preparation choice for ASIT from those currently available on the pharmaceutical market, patient selection criteria, and the issues of modern molecular allergodiagnostic (allergic sensitization mapping of the patient at molecular level), in order to optimize them. Immunological mechanisms of ASIT are also considered, since appropriate views are rather contraversial. The ASIT effect is mediated through the following basic immunological mechanisms: the suppressed increase of the eosinophil concentrations, reduced duration of the delayed hypersensitivity phase, as well as initiation and maintenance of the Th2-to-Th1-like immune response transition. Regulatory T-cells play a major role in implementation of the immunological mechanism in ASIT, they have a significant impact on the Th2 response suppression. Such suppression may proceed via increased production of specific IgG antibodies, primarily of IgG4 subtype. The shift of balance between IgE and IgG4 towards IgG4 production is now considered a fundamental condition for successful ASIT. It has been proven that the allergen-specific IgG4 antibodies against IgE persist after discontinuation of the treatment and can provide long-term clinical tolerance. Modern prospectives for development of new forms and species of preparations for ASIT are also reviewed. Two groups of drugs for ASIT have been adopted for clinical practice until now, i.e., allergens and allergoids (allergens chemically modified by treatment with formaldehyde, in order to enhance their immunogenicity and to reduce the incidence of adverse allergic reactions associated with their application). Immunological mechanisms of SLIT (sublingual immunotherapy) are subjected to special consideration. So far, SLIT is the safest and most promising option of ASIT today, its usage is most expedient in pediatric practice.

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