nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2017-21-6-29-38nefr-310Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSСУБПОПУЛЯЦИИ ИММУННЫХ КЛЕТОК ПРИ ГЛОМЕРУЛИТЕ АЛЛОГРАФТА ПОЧКИ: СОСТАВ И ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕIMMUNE CELL SUBPOPULATIONS IN KIDNEY ALLOGRAFT GLOMERULITIS: COMPOSITION AND PROGNOSTIC SIGNIFICANCEХраброваМ. С.KhrabrovaM. S.

Храброва Мария Сергеевна - кандидат медицинских наук, кафедра пропедевтики внутренних болезней, ассистент.

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54, тел.: (812) 338-01-65

Maria S. Khrabrova - MD, PhD., Department of Propedeutics of Internal Diseases Assistant prof.

197022, Saint-Petersburg, Str. Leo Tolstoy, 17 build 54, +7(812) 338-01-65

hrabrovamc@gmail.comМухаметдиноваА. О.MukhametdinovaA. O.

Мухаметдинова Анастасия Олеговна.

197022, Санкт-Петербург, ул. Л. Толстого, д. 6/8

Anastasiya O. Muhametdinova.

197022, Saint-Petersburg, Str. Leo Tolstoy, 6/8

muhametdinovanastya@mail.ruНабоковА. В.NabokowA. V.

Набоков Александр - кандидат медицинских наук, заместитель директора.

34346, Ганн. Мюнден, Фогельзанг, 105

Dr. med. Alexander Nabokow - Dr. med., vice director.

34346, Hann.Muenden, Vogelsang, 105

a.nabokow@awogsd.deГренеХ.-Й.GröneH.-J.

Германн-Йозеф Грёне – профессор.

69120, Гейдельберг, Им Нойенгеймер Фелд, 280

Hermann-Josef Groene - Prof. Dr. med.

69120, Heidelberg, Im Neuenheimer Feld, 280

h.-j.groene@dkfz.deКлимФ.KliemV.

Клим Фолкер - профессор, директор.

Volker Kliem - Prof. Dr. med., director.

34346, Hann.Muenden, Vogelsang, 105

v.kliem@awogsd.deДобронравовВ. А.DobronravovV. A.

Добронравов Владимир Александрович - доктор медицинских наук, проф., заместитель  директора.

197022, Санкт-Петербург, ул. Л. Толстого, д. 17.

Prof. Vladimir A. Dobronravov - MD, PhD, DSci.

197022, Lva Tostogo str. 17

dobronravov@nephrolog.ruПервый Санкт-Петербургский медицинский университет им. акад. И. П. ПавловаРоссияFirst Pavlov Saint-Petersburg State Medical UniversityRussian FederationНефрологический центр Нижней СаксонииГерманияNephrology center of Lower SaxonyGermanyГерманский центр изучения ракаГерманияGerman center of cancer researchGermanyНИИ нефрологии, Первый Санкт-Петербургский медицинский университет им. акад. И. П. ПавловаРоссияResearch Institute of Nephrology, First Pavlov Saint-Petersburg State Medical UniversityRussian Federation2017281120172162938Copyright © Храброва М.С., Мухаметдинова А.О., Набоков А.В., Грене Х., Клим Ф., Добронравов В.А., 20172017Храброва М.С., Мухаметдинова А.О., Набоков А.В., Грене Х., Клим Ф., Добронравов В.А.Khrabrova M.S., Mukhametdinova A.O., Nabokow A.V., Gröne H., Kliem V., Dobronravov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/310Цель исследования

Цель исследования. Оценить связь уровня инфильтрации клубочка Т-лимфоцитами (CD3+), моноцитами/макрофагами (CD68+), В-лимфоцитами (CD20+) при гломерулите с отдаленным прогнозом аллотрансплантации почки (АТП).

Пациенты и методы

Пациенты и методы. В ретроспективное исследование были включены 97 реципиентов аллографта почки (АП) с морфологически верифицированным гломерулитом. 54,6 % пациентов не имели детектируемых донорспецифических антител (ДСА) на момент биопсии, в 25,8% ДСА были положительны, в 19,6% случаев – не были определены. Морфологические изменения оценивали в соответствии с критериями Banff 2013. После идентификации CD68+-, CD3+-, CD20+-клеток с помощью иммуногистохимического окрашивания биоптатов производили количественный анализ позитивных клеток в гломерулярных капиллярах и рассчитывали их среднее значение на клубочек. Метод Каплана–Мейера и мультивариантный регрессионный анализ Кокса были использованы для оценки связи степени инфильтрации CD68+-, CD3+-, CD20+-клетками с риском потери АП. Медиана периода наблюдения от биопсии составила 51 (8; 72) мес.

Результаты

Результаты. CD68+и CD3+-клетки в клубочках при гломерулите АП выявляли чаще CD20+ -клеток. Степень инфильтрации CD68+-клетками была более выражена при наличии ДСА (p = 0,005), подгруппы с/без ДСА не отличались по количеству CD3+и CD20+-клеток. При CD68+ ≥ 8 клеток на клубочек выживаемость АП была ниже (plog-rank= 0,019), как и при наличии CD3+ ≥ 1 (plog-rank = 0,029). В мультивариантной регрессионной модели Кокса уровень CD68+ в гломерулярных капиллярах (1 клетка/клубочек) являлся независимым предиктором потери АП (p<0,005). ВЫВОДЫ. Гломерулит может быть опосредован реализацией разных механизмов, в том числе эффекторной функцией клеток моноцитарно-макрофагального ряда, что требует дальнейшего изучения. Выявление субпопуляций иммунных клеток, в частности CD68+, при иммуноморфологическом исследовании представляется важным в отношении прогноза АТП и выбора тактики лечения.

The Aim of the  study was  to assess the  association of T-cell  (CD3+),  monocyte/macrophage (CD68+), B-cell  (CD20+)  infiltrates in glomeruli with long-term kidney  allograft survival in patients with renal  allograft (RA) glomerulitis.

Patients  and methods

Patients  and methods.  97 RA recipients with biopsy-proven glomerulitis were enrolled in this retrospective study. 54,6% of patients were negative for donor-specific antibodies (DSA-) at the time of biopsy. DSA were detected in 25,8% of cases (DSA+). For 19,6% of patients DSA evaluation was  unavailable at  the  time  of biopsy. Morphological findings were assessed according to  the Banff 2013  criteria. After immunohistochemical staining for CD68+,  CD3+, CD20+  cells  quantitative assay of positive cells  in glomerular capillaries was performed. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the relationship between intraglomerular CD3+, CD68+,  CD20+ cells and risk of RA loss.

Results

Results. CD68+ and CD3+ cells  were found in glomeruli in RA glomerulitis more frequently than  CD20+  cells. The level of intraglomerular CD68+  cells was higher in DSA+ group (p = 0,005), there was no difference in the level of CD3+ and  CD20+ cells between DSA subgroups. Infiltration of CD68+ ≥ 8 cells per glomerulus was associated with a lower RA survival (p log-rank = 0,019) as well as infiltration of CD3+ ≥ 1 cell per glomerulus (p log-rank = 0,029). The number of glomerular CD68+ (1 cell per glomerulus) was independent predictor of RA loss in multivariate Cox regression model (p ≤ 0,003).

Conclusion

Conclusion. RA glomerulitis could be realized by different immunological pathways including monocytes/macrophages actions that requires further investigations. Immunomorphological evaluation of immune cells subpopulations, in particular CD68+ cells, could be crucial for the evaluation of long-term RA prognosis and appropriate therapeutic approach.

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