rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2017-360-367rsp-2408Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHДинамика уровня FoxP3+ регуляторных Т-лимфоцитов у больных ранним ревматоидным артритом на фоне терапии метотрексатомCHANGES IN THE LEVEL OF FoxP3+ REGULATORY T LYMPHOCYTES IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING METHOTREXATE THERAPYАвдееваА. С.AvdeevaA. S.

115522 Москва, Каширское шоссе, 34А

134A, Kashirskoe Shosse, Moscow 115522

9056249400@mail.ruРубцовЮ. П.RubtsovYu. P.

кафедра биохимии и молекулярной медицины факультета фундаментальной медицины

119192 Москва, Ломоносовский проспект, 31, корп. 5

Department of Biochemistry and Molecular Medicine, Faculty of  Fundamental Medicine

31, Lomonosovsky Prospect, Build. 5, Moscow 119192

ПопковаТ. В.PopkovaT. V.

115522 Москва, Каширское шоссе, 34А

134A, Kashirskoe Shosse, Moscow 115522

ДыйкановД. Т.DyikanovD. T.

кафедра биохимии и молекулярной медицины факультета фундаментальной медицины

119192 Москва, Ломоносовский проспект, 31, корп. 5

Department of Biochemistry and Molecular Medicine, Faculty of  Fundamental Medicine

31, Lomonosovsky Prospect, Build. 5, Moscow 119192

НасоновЕ. Л.NasonovE. L.

115522 Москва, Каширское шоссе, 34А

кафедра ревматологии Института профессионального образования

119991 Москва, ул. Трубецкая, 8, стр. 2

134A, Kashirskoe Shosse, Moscow 115522

Department of Rheumatology, Institute of Professional Education

8, Trubetskaya St., Build. 2, Moscow 119991

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»РоссияM.V. Lomonosov Moscow State UniversityRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology I.M. Sechenov First Moscow State Medical University, Ministry of Health of RussiaRussian Federation201728092017554360367Copyright © Авдеева А.С., Рубцов Ю.П., Попкова Т.В., Дыйканов Д.Т., Насонов Е.Л., 20172017Авдеева А.С., Рубцов Ю.П., Попкова Т.В., Дыйканов Д.Т., Насонов Е.Л.Avdeeva A.S., Rubtsov Y.P., Popkova T.V., Dyikanov D.T., Nasonov E.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2408

Цель – проанализировать влияние терапии метотрексатом (МТ) на процентное и абсолютное содержание FoxP3 регуляторных Т-лимфоцитов (Трег) в периферической крови пациентов с ранним ревматоидным артритом (РА), не получавших ранее МТ.

Материал и методы

Материал и методы. В исследование было включено 45 пациентов с ранним РА (критерии ACR/EULAR 2010 г.), не получавших ранее терапии МТ (в том числе 39 женщин); медиана возраста составила 52,0 [32,5;57,5] года, длительность заболевания – 5 [4; 6] мес, DAS28 – 5,01 [4,18; 5,8], 71,1% больных были позитивны по ревматоидному фактору (РФ) и 88,9% – по антителам к циклическому цитруллинированному пептиду (АЦЦП). Всем больным в качестве первого базисного противовоспалительного препарата (БПВП) был назначен МТ в подкожной форме в начальной дозе 10 мг/нед с быстрой эскалацией до 20–25 мг/нед. Процентное и абсолютное количество Трег (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-;CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; FoxP3+CD274+) определялось методом иммунофлюоресцентного окрашивания и многоцветной проточной цитофлюориметрии.

Результаты и обсуждение

Результаты и обсуждение. Через 24 нед после начала терапии медиана индекса DAS28 составила 3,1 [2,7; 3,62]; SDAI – 7,4 [4,2; 11,4], CDAI – 7,0 [4,0; 11,0]; ремиссия/низкая активность заболевания по DAS28 была достигнута у 22 (56,4%) по SDAI – у 25 (64,1%) больных, отсутствие эффекта терапии МТ по критериям EULAR регистрировалось у 4 (10,3%) пациентов. После 6-месячного курса терапии МТ по группе в целом регистрировалось повышение процентного содержания CD4+клеток (с 45,0 [38,0; 49,2] до 46,8 [39,9;53,2]%); повышение процентного и абсолютного количества CD152+surface с 0,65[0,22; 1,67] до 2,07 [1,11;3,81]% и с 0,0002 [0,0001; 0,0008]•109 до 0,0007 [0,0004; 0,002]•109; умеренное снижение процентного и абсолютного содержания FoxP3+ICOS+ клеток – с 5,3 [2,1; 11,3] до 4,07 [1,6; 6,6]% и с 0,002 [0,001-0,006]•109 до 0,0015 [0,0006-0,003]•109 (p<0,05 во всех случаях).

Заключение

Заключение. Применение МТ при раннем РА сопровождается увеличением пропорции и числа Трег с высоким уровнем маркеров активации, что может свидетельствовать об их повышенной супрессорной активности, более выраженной среди пациентов, достигших ремиссии/низкой активности заболевания на фоне лечения.

Objective

Objective: to analyze the impact of methotrexate (MTX) therapy on percentage and absolute content of FoxP3+ regulatory T lymphocytes (Treg) in the peripheral blood of patients with early rheumatoid arthritis (RA) who had not previously received MTX.

Subjects and methods

Subjects and methods. The investigation included 45 patients with early RA (2010 ACR/EULAR criteria) who had not previously received MTX, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28, 5.01 [4.18; 5.8]; 71.1% of the patients were positive for rheumatoid factor and 88.9% – for anticyclic citrullinated peptide antibodies. As the first disease-modifying antirheumatic drug, all the patients were assigned to receive subcutaneous MTX at an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. The percentage and absolute count of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+) were measured by immunofluorescence staining and multicolor flow cytometry.

Results and discussion

Results and discussion. At 24 weeks after starting the therapy, median DAS28, SDAI, and CDAI were 3.1 [2.7; 3.62], 7.4 [4.2; 11.4], and 7.0 [4.0; 11.0], respectively; DAS28 and SDAI remission/low disease activity was reached by 22 (56.4%) and 25 (64.1%) patients, respectively; 4 (10.3%) patients had no MTX treatment effect according to the EULAR criteria. After a 6-month course of MTX therapy, the whole group had increases in the percentage of CD4+cells (from 45.0 [38.0; 49.2] to 46.8 [39.9; 53.2]%) and in the percentage and absolute number of CD152+surface from 0.65 [0.22; 1.67] to 2.07 [1.11; 3.81]% and from 0.0002 [0.0001; 0.0008]•109 to 0.0007 [0.0004; 0.002]•109, and a moderate decrease in the percentage and absolute content of FoxP3+ICOS+ cells from 5.3 [2.1; 11.3] to 4.07 [1.6;6.6]% and from 0.002 [0.001-0.006]•109 to 0.0015 [0.0006-0.003]•109 (p<0.05 in all cases).

Conclusion

Conclusion. The use of MTX in early RA is accompanied by an increase in the proportion and number of Treg with a high level of activation markers, which may indicate their enhanced suppressor activity that is more pronounced among the patients who have achieved remission/low disease activity during the treatment.

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