mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2016-3-221-230mimmun-1034Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESНЕФРИТОГЕННОСТЬ IgA-СВЯЗЫВАЮЩИХ STREPTOCOCCUS PYOGENES. МОДЕЛИРОВАНИЕ IgA-ГЛОМЕРУЛОНЕФРИТАNEPHRITOGENIC ACTIVITY OF IgA-BINDING STREPTOCOCCUS PYOGENES: AN EXPERIMENTAL MODEL OF IgA GLOMERULONEPHRITISБуроваЛ. А.BurovaL. A.

д.м.н., ведущий научный сотрудник отдела молекулярной микробиологии

PhD, MD (Medicine), Leading Research Associate, Department of Molecular Microbiology

ПигаревскийП. В.PigarevskyP. V.

д.б.н., руководитель отдела общей морфологии

PhD (Biology), Head, Department of General Morphology

СнеговаВ. А.SnegovaV. A.

научный сотрудник отдела общей морфологии

Research Associate, Department of General Morphology

ДупликН. В.DuplikN. V.

к.б.н., научный сотрудник отдела молекулярной микробиологии

PhD (Biology), Research Associate, Department of Molecular Microbiology

ШаленКлаасSchalenKlaas

д.м.н., сотрудник отдела медицинской микробиологии

PhD, MD (Medicine), Department of Medical Microbiology

ТотолянАртем А.TotolianArtem A.

д.м.н., академик РАН, главный научный сотрудник отдела молекулярной микробиологии 197376, Россия, Санкт-Петербург, ул. Академика Павлова, 12. Тел.: 8 (812) 234-68-74

PhD, MD (Medicine), Academician, Russian Academy of Sciences, Main Research Associate, Department of Molecular Microbiology 197376, Russian Federation, St. Petersburg, Acad. Pavlov str, 12. Phone: 7 (812) 234-68-74

totolian@hotmail.comФГБНУ «Институт экспериментальной медицины», Санкт-Петербург, РоссияРоссияInstitute of Experimental Medicine, St. Petersburg, Russian FederationRussian FederationИнститут медицинской микробиологии Лундского Университета, Лунд, ШвецияРоссияDepartment of Medical Microbiology, Lund University, Lund, SwedenRussian Federation201611072016183221230Copyright © Бурова Л.А., Пигаревский П.В., Снегова В.А., Дуплик Н.В., Шален К., Тотолян А.А., 20162016Бурова Л.А., Пигаревский П.В., Снегова В.А., Дуплик Н.В., Шален К., Тотолян А.А.Burova L.A., Pigarevsky P.V., Snegova V.A., Duplik N.V., Schalen K., Totolian A.A.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/1034

Цель настоящего исследования состояла в создании экспериментальной кроличьей модели IgA-нефропатии. Для этого применили подходы, которые ранее с успехом использовались при моделировании постстрептококкового гломерулонефрита (PSGN), а также штаммы Streptococcus pyogenes серотипов М4 и М60, способные в разной степени связывать IgA посредством IgAFc-рецепторного белка микроба.Развитие патологического процесса в почках констатировали у большей части животных, получивших инъекции гемолитического стрептококка генотипа emm60, обладающего выраженной экспрессией IgAFcR-белка. При морфометрическом анализе у шести из 10-ти кроликов удалось обнаружить выраженные морфологические и иммунохимические изменения в почках: (i) массивные отложения IgA в мезангиальных клетках клубочков, атрофию их капиллярной сети и отек тканей; (ii) выраженное отложение С3-компонента комплемента в канальцах; (iii) значительную лимфоцитарную инфильтрацию в корковом и мозговом вещенствах почки на фоне слабой продукции цитокина TNFα. Примечательно, что во всех случаях отсутствовала депозиция IgG, что позволило исключить роль анти-IgA антител, как и других IgG, в патологическом процессе. Альтернативным источником депозиции IgA может быть отложение в ткани IgAв комплексе с IgA FcR микроба, как это было показано ранее шведской группой ученых. Описанные изменения отсутствовали в почках контрольных животных. Совокупность полученных результатов позволяет допустить, что нам удалось создать модель гломерулонефрита, близкую по проявлениям к IgA-нефропатии человека.Они также расширяют наши представления о патогенных функциях IgFc-связывающих белков в генезе патологии, вызываемой Streptococcus pyogenes.

The aim of present study was to arrange an experimental rabbit model for IgA-nephropathy. To this purpose, an approach was attempted which was previously successfully applied in rabbits, aiming for induction of post-streptococcal glomerulonephritis (PSGN). To induce the nephropathy, we used two Streptococcus pyogenes strains of M4 and M60 serotypes which showed differential IgA-binding capacity mediated by the IgAFc microbial receptors. The renal tissue damage was developed in most animals treated with emm60 S. pyogenes characterized by marked IgAFcR expression and higher IgA-binding ability. By means of morphometric analysis. Significant morphological and immunochemical glomerular changes were revealed in 6/10 rabbits, as follows: (i) massive IgA deposition in the mesangial glomerular cells, atrophy of the capillary net, and tissue oedema; (ii) marked C3-complement deposition in proximal and distal tubules; (iii) a significant infiltration of cortical and medullar areas by lymphocytes associated with weak TNFα production. Noteworthy, we did not observe local IgG deposition in any cases, thus allowing to exclude any role of anti-IgG, or other IgG’s in evolution of the pathology. Alternatively, the IgA-deposits may occur due to microbial IgA FcR–IgAcontaining cоmplexes, as earlier shown by the Swedish scientists. The above tissue changes were completely absent in kidneys of control animals. Taken together, these data suggest that we have developed an experimental model similar to IgA-nephropathy in humans. The results also extend our knowledge on pathogenic effects of the IgA Fc-binding proteins of Streptococcus pyogenes.

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