rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2018-423-428rsp-2586Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHОсобенности фенотипа Т-регуляторных клеток при ранней и развернутой стадиях ревматоидного артритаFEATURES OF THE PHENOTYPE OF REGULATORY T CELLS IN EARLY AND ADVANCED RHEUMATOID ARTHRITISАвдееваА. С.AvdeevaA. S.9056249400@mail.ruРубцовЮ. П.RubtsovYu. P.

Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine

ПопковаТ. В.PopkovaT. V.ДыйкановД. Т.DyikanovD. T.

Department of Biochemistry and Molecular Medicine, Faculty of Fundamental Medicine

АлексанкинА. П.AleksankinA. P.НасоновЕ. Л.NasonovE. L.

Department of Rheumatology, Institute of Professional Education

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», МоскваРоссияV.A. Nasonova Research Institute of Rheumatology, MoscowRussian FederationФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», факультет фундаментальной медицины, кафедра биохимии и молекулярной медицины, МоскваРоссияM.V. Lomonosov Moscow State University, MoscowRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский УниверситетРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow; I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, MoscowRussian Federation201808092018564423428Copyright © Авдеева А.С., Рубцов Ю.П., Попкова Т.В., Дыйканов Д.Т., Алексанкин А.П., Насонов Е.Л., 20182018Авдеева А.С., Рубцов Ю.П., Попкова Т.В., Дыйканов Д.Т., Алексанкин А.П., Насонов Е.Л.Avdeeva A.S., Rubtsov Y.P., Popkova T.V., Dyikanov D.T., Aleksankin A.P., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2586

Цель исследования – проанализировать уровни CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+ Т-лимфоцитов, FoxP3+ регуляторных Т-клеток (Трег) и CD19+ В-лимфоцитов у пациентов с ранним и развернутым ревматоидным артритом (РА). Материал и методы. В исследование было включено 45 не получавших ранее метотрексат (МТ-наивных) пациентов с ранним РА и 15 пациентов с развернутым РА. Процентное (ПК) и абсолютное (абс.) количество CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD19+, Трег (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+) определялось методом иммунофлюоресцентного окрашивания и многоцветной проточной цитофлуориметрии. Результаты и обсуждение. У пациентов с ранним РА регистрировалось более низкое, по сравнению со здоровыми донорами, ПК FoxP3+CD25+ клеток, ПК и абс. FoxP3+ ICOS+ клеток, ПК и абс. FoxP3+CD154+ клеток и FoxP3+ CD274+ Т-клеток (p<0,05 во всех случаях). У пациентов с развернутым РА также регистрировалось более низкое, по сравнению со здоровыми донорами, ПК FoxP3+CD25+ клеток, ПК и абс. FoxP3+ ICOS+ клеток, ПК и абс. FoxP3+CD154+ клеток и FoxP3+ CD274+ Т-клеток (p><0,05 во всех случаях). Среди пациентов с развернутым РА регистрировалось более высокое, по сравнению с больными с ранней стадией заболевания, содержание CD4+ лимфоцитов (50,7 [44,4; 53,1] и 45,0 [38,0; 49,2]) и более низкое ПК CD25+CD127- Т-лимфоцитов (5,0 [4,0; 5,7] и 6,5 [5,1; 7,9]; p><0,05 во всех случаях). Заключение. У пациентов с РА (как с ранней, так и развернутой стадией заболевания) наблюдается снижение как уровня, так и функциональной активности Трег. У больных с развернутой стадией заболевания, по сравнению с пациентами с ранней стадией РА, регистрируется повышение уровня CD4+ лимфоцитов и более низкий уровень CD25+CD127- клеток, что свидетельствует о более выраженных нарушениях гомеостаза Трег при развернутой стадии РА. Ключевые слова: ранний ревматоидный артрит; Т-лимфоциты; В-лимфоциты; Т-регуляторные клетки><0,05 во всех случаях). У пациентов с развернутым РА также регистрировалось более низкое, по сравнению со здоровыми донорами, ПК FoxP3+CD25+ клеток, ПК и абс. FoxP3+ ICOS+ клеток, ПК и абс. FoxP3+CD154+ клеток и FoxP3+ CD274+ Т-клеток (p<0,05 во всех случаях). Среди пациентов с развернутым РА регистрировалось более высокое, по сравнению с больными с ранней стадией заболевания, содержание CD4+ лимфоцитов (50,7 [44,4; 53,1] и 45,0 [38,0; 49,2]) и более низкое ПК CD25+CD127- Т-лимфоцитов (5,0 [4,0; 5,7] и 6,5 [5,1; 7,9]; p><0,05 во всех случаях). Заключение. У пациентов с РА (как с ранней, так и развернутой стадией заболевания) наблюдается снижение как уровня, так и функциональной активности Трег. У больных с развернутой стадией заболевания, по сравнению с пациентами с ранней стадией РА, регистрируется повышение уровня CD4+ лимфоцитов и более низкий уровень CD25+CD127- клеток, что свидетельствует о более выраженных нарушениях гомеостаза Трег при развернутой стадии РА. Ключевые слова: ранний ревматоидный артрит; Т-лимфоциты; В-лимфоциты; Т-регуляторные клетки><0,05 во всех случаях). Среди пациентов с развернутым РА регистрировалось более высокое, по сравнению с больными с ранней стадией заболевания, содержание CD4+ лимфоцитов (50,7 [44,4; 53,1] и 45,0 [38,0; 49,2]) и более низкое ПК CD25+CD127- Т-лимфоцитов (5,0 [4,0; 5,7] и 6,5 [5,1; 7,9]; p<0,05 во всех случаях). Заключение. У пациентов с РА (как с ранней, так и развернутой стадией заболевания) наблюдается снижение как уровня, так и функциональной активности Трег. У больных с развернутой стадией заболевания, по сравнению с пациентами с ранней стадией РА, регистрируется повышение уровня CD4+ лимфоцитов и более низкий уровень CD25+CD127- клеток, что свидетельствует о более выраженных нарушениях гомеостаза Трег при развернутой стадии РА. Ключевые слова: ранний ревматоидный артрит; Т-лимфоциты; В-лимфоциты; Т-регуляторные клетки><0,05 во всех случаях). Заключение. У пациентов с РА (как с ранней, так и развернутой стадией заболевания) наблюдается снижение как уровня, так и функциональной активности Трег. У больных с развернутой стадией заболевания, по сравнению с пациентами с ранней стадией РА, регистрируется повышение уровня CD4+ лимфоцитов и более низкий уровень CD25+CD127- клеток, что свидетельствует о более выраженных нарушениях гомеостаза Трег при развернутой стадии РА.

Objective

Objective: to analyze the levels of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD56+ T lymphocytes, FoxP3+ regulatory T cells (Treg), and CD19+ B lymphocytes in patients with early and advanced rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 45 patients previously untreated with methotrexate (MTX-naive) who had early RA and 15 patients who had advanced RA. Immunofluorescence staining and multicolor flow cytometry assays were used to estimate the percentage and absolute (abs) counts of CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD19+, Treg (FoxP3+CD25+; surface CD152+; intracellular CD152+; FoxP3+CD127; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+. Results and discussion. The patients with early RA were found to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs counts of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells than healthy donors (p<0.05 in all cases). The patients with advanced RA were also recorded to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs contents of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells (p><0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). The patients with advanced RA were also recorded to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs contents of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells (p<0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p<0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA. Keywords: early rheumatoid arthritis; T lymphocytes; B lymphocytes; regulatory T cells><0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA.

 

 

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