mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2020-2-20-26mrj-1009Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSДинамика субпопуляций лимфоцитов, CD4+CD25+CD127- Т-регуляторных клеток у больных ревматоидным артритом на фоне терапии биоаналогом ритуксимаба (Ацеллбия)Dynamics of lymphocyte subpopulations, CD4+CD25+CD127- T regulatory cells in patients with rheumatoid arthritis during therapy with the rituximab biosimilar AcellbiaАвдееваА. С.AvdeevaA. S.

Анастасия Сергеевна Авдеева

115522, Москва, Каширское шоссе, 34А

Anastasia Sergeevna Avdeeva

34A, Kashirskoe Shosse, Moscow 115522

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

лаборатория биокатализа

117997, Москва, ул. Миклухо-Маклая, 16/10

Laboratory of Biocatalysis

16/10, Miklukho-Maklai St., Moscow 117997

ЧеркасоваМ. В.CherkasovaM. V.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

НасоновЕ. Л.NasonovE. L.

115522, Москва, Каширское шоссе, 34А119991, Москва, ул. Трубецкая, 8, стр. 2

34A, Kashirskoe Shosse, Moscow 1155228, Trubetskaya St., Build. 2, Moscow 119991

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБУН «Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук» Минобрнауки РоссииРоссияAcademicians M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ministry of Education and Science of RussiaRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of RussiaRussian Federation2020290520201422026Copyright © Авдеева А.С., Рубцов Ю.П., Черкасова М.В., Насонов Е.Л., 20202020Авдеева А.С., Рубцов Ю.П., Черкасова М.В., Насонов Е.Л.Avdeeva A.S., Rubtsov Y.P., Cherkasova M.V., 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://mrj.ima-press.net/mrj/article/view/1009

Цель исследования – оценка влияния биоаналога ритуксимаба (РТМ, Ацеллбия) на содержание CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- лимфоцитов в периферической крови пациентов с ревматоидным артритом (РА).Пациенты и методы. Обследовано 20 больных РА, получивших по 2 инфузии РТМ в суммарной дозе 1200 мг. Уровень СРБ, IgM ревматоидного фактора, IgG, IgM, IgA определялся нефелометрическим методом. Относительное и абсолютное содержание CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- Т-регуляторных клеток (Т-рег) – методом многоцветной проточной цитофлюориметрии.Результаты и обсуждение. К 24-й неделе терапии РТМ хороший/удовлетворительный эффект по критериям EULAR отмечался у 17 (85%) пациентов; ремиссия по DAS28 – у 4 (20%), ремиссия по SDAI – у 2 (10%). Применение РТМ сопровождалось достоверным повышением относительного содержания CD4+CD25+CD127-Т-лимфоцитов, медиана которого через 12 и 24 нед после начала терапии увеличилась с 6,8 [5,2; 7,6] % до 7,3 [6,1; 8,3] и 6,97 [6,4; 8,2] % соответственно (р<0,05). Отмечалась тенденция к повышению абсолютного содержания Т-рег в периферическом кровотоке через 12 нед после первой инфузии препарата (до 0,05 [0,04; 0,075] •109 /л; р=0,05). Среди пациентов, достигших ремиссии/низкой активности заболевания по SDAI к 24-й неделе наблюдения, исходное относительное содержание Т-рег было значимо выше – 7,35 [6,8; 7,97] % по сравнению с группой больных с умеренной активностью патологического процесса – 5,8 [4,3; 7,22] %; р<0,05.Заключение. Применение биоаналога РТМ сопровождается развитием полной деплеции CD19+ лимфоцитов, повышением числа CD3+ и CD3+CD4+ лимфоцитов, а также Т-рег. Большее исходное количество CD4+CD25+CD127- лимфоцитов ассоциируется с более высокой эффективностью терапии РТМ.

Objective: to evaluate the effect of the rituximab (RTM) biosimilar Acellbia on the peripheral blood levels of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, and CD4+CD25+CD127- lymphocytes in patients with rheumatoid arthritis (RA).Patients and methods. Examinations were made in 20 RA patients who received 2 RTM infusions at a total dose of 1200 mg. The levels of C-reactive protein, IgM rheumatoid factor, IgG, IgM, and IgA were measured by a nephelometric method. The relative and absolute contents of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- T regulatory cells (Tregs) were estimated by multicolor flow cytofluorometry.Results and discussion. At week 24 of RTM therapy, there was a good/satisfactory effect according to EULAR criteria in 17 (85%) patients; DAS28 remission in 4 (20%), and SDAI remission in 2 (10%). The use of RTM was accompanied by a significant increase in the relative content of CD4+CD25+CD127- T lymphocytes, the median of which at weeks 12 and 24 after therapy initiation increased from 6.8 [5.2; 7.6]% to 7.3 [6.1; 8.3] and 6.97 [6.4; 8.2]%, respectively (p<0.05). The absolute peripheral blood count of Tregs tended to increase at weeks 12 after the first infusion of the drug (up to 0.05 [0.04; 0.075] ⋅ 109 /l; p=0.05). At week 24 follow-up, the patients who achieved SDAI remission/low disease activity had significantly higher baseline relative Tregs levels (7.35 [6.8; 7.97]% than those with the moderate activity of the pathological process (5.8 [4.3; 7.22] %; p<0.05).Conclusion. The use of the RTM biosimilar is accompanied by the development of complete depletion of CD19+ lymphocytes and by an increase in CD3+ and CD3+CD4+ lymphocytes and Tregs. The larger baseline number of CD4+CD25+CD127- lymphocytes is associated with the higher efficiency of RTM therapy.

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