mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-CCA-2520mimmun-2606Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКлеточный состав и цитокиновый профиль синовиальной жидкости при ревматоидном артритеСellular composition and cytokine profile of synovial fluid in rheumatoid arthritisЖдановаЕ. В.ZhdanovaE. V.

Жданова Екатерина Васильевна, д.м.н., профессор, заведующая кафедрой патологической физиологии

625027, г. Тюмень, ул. Котовского, 5/2Тел.: 8 (3452) 20-00-61

Zhdanova Ekaterina V. PhD, MD (Medicine), Professor, Head, Department of Pathological Physiology

625027, Tyumen, Kotovsky str., 5/2Phone: 7 (3452) 20-00-61

lenakost@mail.ruКостоломоваЕ. Г.KostolomovaE. G.

к.б.н., доцент кафедры микробиологии

г. Тюмень

PhD (Biology), Associate Professor, Department of Microbiology

Tyumen

ВолковаД. Е.VolkovaD. E.

студентка лечебного факультета

г. Тюмень

Student, Faculty of Medicine

Tyumen

ЗыковА. В.ZykovA. V.

студент лечебного факультета

г. Тюмень

Student, Faculty of Medicine

Tyumen

ФГБОУ ВО «Тюменский государственный медицинский университет» Министерства здравоохранения РФРоссияTyumen State Medical UniversityRussian Federation20220511202224510171026Copyright © Жданова Е.В., Костоломова Е.Г., Волкова Д.Е., Зыков А.В., 20222022Жданова Е.В., Костоломова Е.Г., Волкова Д.Е., Зыков А.В.Zhdanova E.V., Kostolomova E.G., Volkova D.E., Zykov A.V.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/2606

Ревматоидный артрит занимает первое место среди хронических заболеваний суставов. Часто поражая лиц трудоспособного возраста, заболевание сопровождается значительным снижением качества жизни пациентов и их ранней инвалидизацией.

Ревматоидный артрит является иммуновоспалительным ревматическим заболеванием, следовательно, иммунная система обеспечивает формирование очага первичного повреждения, его персистенцию и периодическое обострение. Выяснение характера межклеточных взаимоотношений, опосредуемых с помощью цитокинов, на различных этапах хронического воспалительного процесса необходимо для разработки иммунотерапевтических подходов как для купирования обострения, так и поддержания ремиссии.

Цель исследования – оценить клеточный состав и цитокиновый профиль синовиальной жидкости у пациентов с ревматоидным артритом в стадии обострения и ремиссии.

В образцах синовиальной жидкости 60 больных ревматоидным артритом, 30 из которых находились в стадии обострения и 30 в стадии ремиссии, исследовали клеточный состав и цитокиновый профиль. В стадии обострения находились 21 женщина и 9 мужчин, их средний возраст составил 57,0±15,4 года, с длительностью болезни 8,55±6,9 года. Средний возраст 19 женщин и 11 мужчин, находившихся в стадии ремиссии, составил 53,5±10,9 года, длительность болезни 6,9±5,8 года.

Фенотипирование лейкоцитов осуществляли на проточном цитофлуориметре CytoFLEX (Beckman Coulter, США). Содержание цитокинов определяли иммуноферментным методом с использованием стандартного набора реактивов ООО «Протеиновый контур» (Россия). Регистрацию результатов проводили на фотометре Multiskan (Labsystems, Финляндия).

Во время обострения содержание лейкоцитов в синовиальной жидкости увеличилось в 2,4 раза по сравнению с ремиссией. Клеточный инфильтрат был представлен нейтрофилами, при этом содержание лимфоцитов и моноцитов не изменилось. Усиленная миграция нейтрофилов сопровождалась возрастанием уровней TNFα в 8 раз, по сравнению с ремиссией, и IL-1β – в 6,3 раза. Абсолютное количество CD3+Т-лимфоцитов, CD16+CD56+В-клеток и CD3-CD19+NK при обострении было таким же, как и в ремиссии, однако при этом изменялась численность субпопуляций Т-лимфоцитов: число CD4+ лимфоцитов уменьшалась, а CD8+ возрастало, а также достоверно увеличивалось количество Treg-лимфоцитов и NKT-клеток. Увеличением в 4,3 раза концентрации IL-4 во время обострения свидетельствовало о преобладании Th2-иммунного ответа. Во время ремиссии в синовиальной жидкости в 1,5 раза возрастала концентрация IL-6 и в 2,5 раза IFNγ, что характерно для активации Th1-ответа.

Rheumatoid arthritis (RA) ranks first among chronic joint diseases. The disease often affects people at their working age, being accompanied by significant decrease in the life quality of patients and their early disability. Rheumatoid arthritis is an immunoinflammatory rheumatic disease. Therefore, the immune system provides evolving focus of primary damage, its persistence and periodic exacerbation. Elucidation of intercellular relationships mediated by cytokines at various stages of the chronic inflammatory process is required in order to develop immunotherapeutic approaches, aimed for both recovery from exacerbations and maintenance of remission state. Purpose of our study was to evaluate cellular composition and cytokine profile of synovial fluid in the patients with rheumatoid arthritis at acute phase and in remission state.

We have studied the samples of synovial fluid taken in 60 patients with rheumatoid arthritis, with 30 subjects being at acute stage of the disease, and 30 patients in remission. Cellular composition and cytokine profile were assessed in the clinical samples. There were 21 women and 9 men at the acute stage (57.0±15.4 years old), with the disease duration of 8.55±6.9 years. The average age of 19 women and 11 men examined in remission state was 53.5±10.9 years, with comparable duration of illness (6.9±5.8 years). The leukocyte phenotyping was performed with a CytoFLEX flow cytometer (Beckman Coulter, USA). The cytokine contents were measured by enzyme immunoassay using a standard set of reagents from the “Proteinovy Contour” LLC (Russia). The results were registered by a Multiscan photometer (Labsystems, Finland).

During the disease exacerbation, the leukocyte contents in synovial fluid increased 2.4-fold, as compared to the remission values. The cellular infiltrate was represented by neutrophils, whereas the contents of lymphocytes and monocytes did not change. Increased migration of neutrophils was accompanied by an 8-fold increase in TNFα levels, compared with remission state, and IL-1β levels were increased by 6.3 times. The absolute number of CD3+T lymphocytes, CD16+CD56+B cells, and CD3-CD19+NK during exacerbation was similar to the remission levels. However, the number of T cell subpopulations was changed, i.e., the number of CD4+ lymphocytes was decreased, and CD8+ cell counts were increased, like as numbers of Treg lymphocytes and NKT cells which showed a significant increase. A 4.3-fold increase in the IL-4 concentration during the RA exacerbation suggested the predominance of Th2 immune response. During remission, the concentrations of IL-6 and IFNγ in synovial fluid were increased, respectively, by 1.5 times and by 2.5 times, which is typical for activated Th1 response.

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