ПАТОГЕНЕТИЧЕСКАЯ ОСЬ ЖЕЛУДОЧНО-КИШЕЧНЫЙ ТРАКТ-ПОЧКИ В РАЗВИТИИ И ПРОГРЕССИРОВАНИИ IGA НЕФРОПАТИИ (Обзор литературы)

Аннотация

IgA нефропатия (IgAН) — наиболее частый вариант первичных гломерулонефритов, диагностическим критерием которого является морфологическая верификация IgA в мезангии почечных клубочков. В соответствии с современными представлениями IgAН рассматривают как аутоиммунную патологию, ключевую роль в развитии которой играет гиперпродукция галактозодефицитного IgA1. Принимая во внимание, что приоритетными в выработке IgA1 в ответ на стимуляцию антигенами являются слизистые желудочно-кишечного тракта (ЖКТ), важное значение в патогенезе IgAН приобретает состояние микробиоты слизистых, которая наряду с ее метаболитами, влияет на формирование иммунного ответа. Гиперактивность ЖКТ, и особенно кишечника, как свидетельствуют данные экспериментальных и клинических исследований, играет определяющую роль не только в развитии, но и прогрессировании IgAН. По данным полногеномного ассоциативного исследования у пациентов с IgAН была выявлена связь между генетической вероятностью развития IgAН и локальной микробиотой. В частности, при IgAН было отмечено возрастание числа Proteobacteria, которые вследствие избыточной продукции липополисахаридов способны подавлять экспрессию гена мРНК специфического молекулярного шаперона (Cosmc), необходимого для процесса гликозилирования IgA1. Кроме того, в геноме IgAН пациентов с были выделены локусы, ответственные за проницаемость кишечника и иммунный ответ слизистой оболочки, а также локусы. ассоциированные с риском развития воспалительных заболеваний кишечника. Последние, в свою очередь, при выявлении причинно-следственных связей с применением метода менделевской рандомизации повышали вероятность возникновения IgAН.
Определение относительной численности отдельных типов бактерий, а также уровня их метаболитов, которые могли бы стать неинвазивными биомаркерами активности IgAН, представляется актуальным направлением будущих исследований. В продолжении изучения нуждается и уточнение механизмов взаимодействия отдельных звеньев сложного этиопатогенеза IgAН, которое позволит разработать стратегически новые подходы к лечению.

Annotation

IgA nephropathy (IgAN) is the most common variant of primary glomerulonephritis, the diagnostic criterion of which is morphological verification of IgA in the mesangium of the renal glomeruli. In accordance with modern concepts, IgAN is considered an autoimmune pathology, the key role in the development of which is played by hyperproduction of galactose-deficient IgA1. Taking into account that the mucous membranes of the gastrointestinal tract (GIT) are the priority in the production of IgA1 in response to stimulation with antigens of various nature, the state of the microbiota of the mucous membranes, which, along with its metabolites, affects the formation of the immune response, is of great importance in the pathogenesis of IgAN. Hyperactivity of the gastrointestinal tract, and especially the intestines, as evidenced by experimental and clinical studies, plays a decisive role not only in the development, but also in the progression of IgAN. Analysis of the results of a genome-wide association study in patients with IgAN revealed a link between the genetic probability of developing IgAN and the local microbiota. In particular, with IgAN, an increase in the number of Proteobacteria was noted, which, due to excessive production of lipopolysaccharides, are able to suppress the expression of the mRNA gene of a specific molecular chaperone (Cosmc), necessary for the process of glycosylation of IgA1. In addition, in the genome of IgAN patients, loci responsible for intestinal permeability and the immune response of the mucosa, as well as loci associated with the risk of developing inflammatory bowel diseases, were identified. The latter, in turn, when identifying cause-and-effect relationships using the Mendelian randomization method, increased the likelihood of IgAN.
Determination of the relative abundance of individual bacterial types, as well as the level of their metabolites, which could become noninvasive biomarkers of IgAN activity, seems to be an important direction for future research. Further study is also needed to clarify the mechanisms of interaction between individual links in the complex etiopathogenesis of IgAН, which will allow the development of strategically new approaches to treatment.
Key words: IgA nephropathy; galactose-deficient IgA1; microbiota; review

Об авторах

Список литературы

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