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Том 26 №1 2024 год - Нефрология и диализ

Современные представления о патогенезе IgA нефропатии

Зубкин М.Л. Солдатов Д.А. Фролова Н.Ф. Червинко В.И. Крюков Е.В.

DOI: 10.28996/2618-9801-2024-1-35-54

Аннотация: Введение: иммуноглобулин А нефропатия является самым распространенным в мире и в России первичным хроническим гломерулонефритом и одной из наиболее значимых причин развития терминальной стадии хронической болезни почек, требующей применения заместительной почечной терапии. Заболевание дебютирует у людей преимущественно молодого и трудоспособного возраста (от 20 до 40 лет), что определяет его социальную значимость. Также известно о высокой частоте рецидивов IgA нефропатии после трансплантации донорской почки. Спектр клинических проявлений и морфологической картины заболевания чрезвычайно разнообразен, варьируя от изолированного мочевого синдрома (асимптоматическая микрогематурия/протеинурия) до нефритической активности, нефротического синдрома и даже быстропрогрессирующего гломерулонефрита. Цель настоящего обзора представить современный взгляд на патогенез IgA нефропатии. Основные сведения: в настоящее время сформировалось принципиальное понимание природы этого заболевания, а также появились отдельные данные о более тонких механизмах его развития. Стало очевидным, что IgA нефропатия является аутоиммунной болезнью, в основе которой лежит образование иммунных комплексов (ИК). В роли аутоантигена выступает галактозо-дефицитный IgA1 (Gd-IgA1), образующийся в результате ослабленного гликозилирования отдельных участков шарнирной области тяжелых цепей этого иммуноглобулина. Его продукция осуществляется клетками MALT-системы (mucosa-associated lymphoid tissue), а именно лимфоидной ткани миндалин ротоглотки NALT (nasal-associated lymphoid tissue) и дистального отдела тонкого кишечника GALT (gut-associated lymphoid tissue). Однако в последние годы значительную роль в патогенезе IgA нефропатии отводят так называемой оси «кишечник-почка». ИК, связываясь с особыми рецепторами, расположенными на мезангиоцитах почечного клубочка, запускают процесс его повреждения. В представленном научном обзоре приводится информация о структуре и продукции IgA как в норме, так и в условиях, способствующих развитию патологии. Рассматриваются триггеры недогликозилирования IgA1, в частности, роль хронических заболеваний носоглотки и кишечника, значение состояния микробиоты этих отделов желудочно-кишечного тракта и пищевых антигенов. Новые данные о патогенезе IgA нефропатии лежат в основе разрабатываемых и уже апробируемых методов лечения заболевания и поэтому могут представлять интерес для клиницистов. Например, крупное международное многоцентровое рандомизированное двойное слепое плацебо-контролируемое клиническое исследование NefigArd продемонстрировало эффективность глюкокортикостероидного препарата (будесонид/Nefecon) с таргетным высвобождением в дистальном отделе тонкого кишечника при существенно меньшей частоте нежелательных явлений, свойственных системным кортикостероидам.

Для цитирования: Зубкин М.Л., Солдатов Д.А., Фролова Н.Ф., Червинко В.И., Крюков Е.В. Современные представления о патогенезе IgA нефропатии. Нефрология и диализ. 2024. 26(1):35-54. doi: 10.28996/2618-9801-2024-1-35-54

Весь текст

Ключевые слова: IgA нефропатия, галактозо-дефицитный IgA1, иммунные комплексы, триггеры, IgA nephropathy, galactose-deficient IgA1, immune complexes, triggers

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