mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SCO-2552mimmun-2552Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСубпопуляционный состав лимфоцитов периферической крови при COVID-19Subpopulation composition of peripheral blood lymphocytes in COVID-19СвирщевскаяЕ. В.SvirshchevskayaE. V.

Свирщевская Елена Викторовна – кандидат биологических наук, старший научный сотрудник отдела иммунологии ИБХ РАН им. ак. М.М. Шемякина и Ю.А. Овчинникова РАН; старший научный сотрудник НМИЦ акушерства, гинекологии и перинатологии им. ак. В.И. Кулакова МЗ РФ.

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

Тел.: 8 (910) 464-87-60

Elena V. Svirshchevskaya - PhD (Biology), Senior Research Associate, Department of Immunology, Shemyakin– Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Senior Research Associate, V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

16/10 Miklukho-Maclay St Moscow 117997

Phone: +7 (910) 464-87-60

esvir@mail.ibch.ruКоноваловаМ. В.KonovalovaM. V.

Коновалова Мария Владимировна – кандидат биологических наук, научный сотрудник отдела иммунологии.

Москва

Maria V. Konovalova - PhD (Biology), Research Associate, Department of Immunology, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences.

Moscow

mariya.v.konovalova@gmail.comhttps://orcid.org/0000-0002-3511-5292СадыковВ. Ф.SadykovV. F.

Садыков Валентин Фидаильевич – аспирант.

Москва

Valentin F. Sadykov - Postgraduate Student, V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Moscow

valentinsadykov@yandex.ruПыреговА. В.PyregovA. V.

Пырегов Алексей Викторович – доктор медицинских наук, директор института анестезиологии-реаниматологии и трансфузиологии, заведующий кафедрой анестезиологии и реаниматологии.

Москва

Aleksey V. Pyregov - PhD, MD (Medicine), Director of the Institute of Anesthesiology-Resuscitation and Transfusiology, Head of the Department of Anesthesiology and Resuscitation, V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Moscow

pyregov@mail.ruПолтавцеваР. А.PoltavtsevaR. A.

Полтавцева Римма Алексеевна – кандидат биологических наук, ведущий научный сотрудник.

Москва

Rimma A. Poltavtseva - PhD (Biology), Leading Research Associate, V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Moscow

rimpol@mail.ruИнститут биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук; Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова Министерства здравоохранения РФРоссияShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; V. Kulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyRussian FederationИнститут биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наукРоссияShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesRussian FederationНациональный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова Министерства здравоохранения РФРоссияV. Kulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyRussian Federation202318112022251155166Copyright © Свирщевская Е.В., Коновалова М.В., Садыков В.Ф., Пырегов А.В., Полтавцева Р.А., 20232023Свирщевская Е.В., Коновалова М.В., Садыков В.Ф., Пырегов А.В., Полтавцева Р.А.Svirshchevskaya E.V., Konovalova M.V., Sadykov V.F., Pyregov A.V., Poltavtseva R.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2552

Патогенез тяжелой коронавирусной инфекции COVID-19 ассоциирован с активацией иммунной системы, цитокиновым штормом, нарушением гемостаза крови, микрососудистым тромбозом, ишемией органов и синдромом полиорганной дисфункции. Роль различных субпопуляций при COVID-19 до сих пор дискутируется. Целью исследования являлся анализ субпопуляционного состава лимфоцитов периферической крови больных COVID-19 по сравнению со здоровыми донорами. В исследование включили 20 больных COVID-19 (11 мужчин и 9 женщин) и 26 здоровых доноров. Средний возраст больных составил 52 и 56 лет соответственно. Лимфоциты периферической крови выделяли на градиенте фиколла. Клетки окрашивали антителами к основным популяциям лимфоцитов, маркерам эндотелиальных клеток и апоптоза. Анализ проводили методом проточной цитометрии. Клинические данные получены стандартными лабораторными методами. Результаты показали, что у всех больных были повышены C-реактивный белок (в 14-35 раз), ферритин (в 1,2-13 раз), D-Димеры (в 1,2-90 раз). У 55% мужчин наблюдали снижение абсолютного числа лимфоцитов, у женщин этот показатель находился на нижней границе нормы. Цитометрический анализ показал, что среди лимфоцитов периферической крови доля функциональных клеток, экспрессирующих маркер CD45, у 70% больных составляла от 2 до 12% при 80-99% у всех доноров. Доля CD45+ лимфоцитов достоверно коррелировала с уровнем гемоглобина, но не с уровнями воспалительных биохимических маркеров. Среди функциональных лимфоцитов больных наблюдали снижение доли CD3+, CD4+, CD8+Т-клеток, увеличение доли натуральных киллеров CD56+ и уровня апоптотических клеток AnnexinV+, но не было изменения в доле В-клеток CD19 и HLA-DR+. Анализ субпопуляций ЛЦ, не экспрессирующих маркер CD45, показал наличие в этой фракции всех популяций лимфоцитов со сниженной экспрессией CD4, CD8, CD19, CD56 и других в крови больных и доноров. Отличием между больными и донорами был высокий процент эндотелиальных клеток, экспрессирующих маркер CD62P.

Определение лабораторными методами количества лимфоцитов в крови больных COVID-19 не отражает реальную картину тяжести заболевания и требует определения доли функциональных клеток, экспрессирующих CD45.

The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors.

The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors.

Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.

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