Studies of CD45+ and CD46+ expression on the peripheral blood lymphocyte subsets of the post-COVID patients
- Authors: Dobrynina M.A.1, Zurochka A.V.1,2, Komelkova M.V.1,2, Luo S.3, Zurochka V.A.1,2, Desheng H.3, Ryabova L.V.4, Sarapultsev A.P.1,2
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Affiliations:
- Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences
- South Ural State University (National Research University)
- University of Science and Technology
- South Ural State Medical University
- Issue: Vol 25, No 4 (2022)
- Pages: 431-436
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/120071
- DOI: https://doi.org/10.46235/1028-7221-1160-SOC
- ID: 120071
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Abstract
The SARS-CoV-2 virus can enter the cells using S1 viral spike (S) protein, not only by binding to ACE2, but also through other cellular receptors. These candidate receptors include CD46, which, like CD45, belongs to pan-leukocyte receptors and is expressed on all types of lymphocytes. In turn, SARS-CoV-2 infection is accompanied by damage to almost all compartments of the immune system, mainly T lymphocytes. The purpose of the study was to evaluate the expression levels of CD45+ and CD46+ in various subpopulations of lymphocytes in patients who had undergone SARS-CoV-2 infection.
72 patients who had undergone SARS-CoV-2 infection were examined. Using flow cytometry technique, we determined CD45+ and CD46+ (panleukocyte marker for lymphocyte gating), CD45+ and CD46+, CD3+ (T lymphocytes), CD45+ and CD46+, CD3+, CD4+ (helper inducers), CD45+ and CD46+, CD3+, CD8+ (cytotoxic T-lymphocytes), CD45+ and CD46+, CD3+, CD56+ (TNK cells) CD45+ and CD46+, CD3-, CD56+ (natural killers), CD45+ and CD46+, CD3-, CD19+ (B lymphocytes), CD45+ and CD46+, CD3+, CD4+, CD25+ (activated helpers, early activation of lymphocytes), CD45+ and CD46+, CD3+, HLA-DR (activated T lymphocytes – late activation of lymphocytes). Our studies have shown that a decrease in CD46+ expression in T lymphocytes (CD3+) is accompanied by similar decrease of its expression in cytotoxic T lymphocytes (CD3+, CD8+), TNK (CD3+, CD56+), as well as in helpers T carrying markers of early activation (CD3+, CD4+, CD25+). At the same time, the most pronounced decrease was observed both among total T lymphocytes and cytotoxic T cells. In these patients, the expression level of CD46+ in B lymphocytes was slightly increased. Recent data suggest that there is no involvement of CD46 receptor on B lymphocytes. Our data suggest that the SARS-CoV-2 virus may affect the CD46 receptor. Such exposure may lead to promotion of the long-COVID (post-COVID) symptoms in such patients, thus requiring new approaches to correction of these disorders.
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##article.viewOnOriginalSite##About the authors
M. A. Dobrynina
Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences
Author for correspondence.
Email: mzurochka@mail.ru
PhD (Medicine), Junior Research Associate, Laboratory of Inflammation Immunology
Russian Federation, EkaterinburgA. V. Zurochka
Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; South Ural State University (National Research University)
Email: mzurochka@mail.ru
PhD, MD (Medicine), Professor, Leading Research Associate, Laboratory of Inflammation Immunology; Head, Laboratory of Immune Biotechnology, Russian-Chinese Educational Center
Russian Federation, Ekaterinburg; ChelyabinskM. V. Komelkova
Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; South Ural State University (National Research University)
Email: mzurochka@mail.ru
PhD (Biology), Head, Laboratory of Systemic Pathology and Prospective Medical Drugs, Russian-Chinese Educational Center; Senior Research Associate, Laboratory of Immune Physiology and Immunopharmacology
Russian Federation, Ekaterinburg; ChelyabinskSh. Luo
University of Science and Technology
Email: mzurochka@mail.ru
Professor, Institute of Hematology, Union Hospital, Tongji Medical College
China, WuhanV. A. Zurochka
Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; South Ural State University (National Research University)
Email: mzurochka@mail.ru
PhD, MD (Medicine), Senior Research Associate, Laboratory of Inflammation Immunology; Senior Research Associate, Laboratory of Immune Biotechnology, Russian-Chinese Educational Center
Russian Federation, Ekaterinburg; ChelyabinskHu Desheng
University of Science and Technology
Email: mzurochka@mail.ru
Professor, Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College
China, WuhanL. V. Ryabova
South Ural State Medical University
Email: mzurochka@mail.ru
PhD, MD (Medicine), Professor, Department of Life Security, Emergency Medicine, First Aid and Urgent Care
Russian Federation, ChelyabinskA. P. Sarapultsev
Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; South Ural State University (National Research University)
Email: mzurochka@mail.ru
PhD, MD (Biology) Leading Research Associate, Laboratory of Immunopathophysiology; Director, Russian-Chinese Educational Center
Russian Federation, Ekaterinburg; ChelyabinskReferences
- Зурочка А.В., Хайдуков С.В., Кудрявцев И.В., Черешнев В.А. Проточная цитометрия в биомедицинских исследованиях. Екатеринбург: РИО УрО РАН, 2018. 720 с. [Zurochka A.V., Khaidukov S.V., Kudryavtsev I.V., Chereshnev V.A. Flow cytometry in biomedical research]. Ekaterinburg: RIO Ural Branch of the Russian Academy of Sciences, 2018. 720 p.
- Хайдуков С.В., Байдун Л.А., Зурочка А.В., Тотолян А.А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» // Российский иммунологический журнал, 2014, Т. 8 (17), № 4. С. 974-992. [Khaydukov S.V., Baidun L.A., Zurochka A.V., Totolyan A.A. Standardized technology “Study of the subpopulation composition of peripheral blood lymphocytes using flow cytofluorometer-analyzers”. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2014, Vol. 8 (17), no. 4, pp. 974-992. (In Russ.)]
- Gusev E., Sarapultsev A., Solomatina L., Chereshnev V. SARS-CoV-2-Specific immune response and the pathogenesis of COVID-19. Int. J. Mol. Sci., 2022, Vol. 23, no. 3, 1716. doi: 10.3390/ijms23031716.
- Jouan Y., Guillon A., Gonzalez L., Perez Y., Boisseau C., Ehrmann S., Ferreira M., Daix T., Jeannet R., François B., Dequin P.F., Si-Tahar M., Baranek T., Paget C. Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients. J. Exp. Med., 2020, Vol. 217, no. 12, e20200872. doi: 10.1084/jem.20200872.
- Kunz N., Kemper C. Complement has brains-do intracellular complement and immunometabolism cooperate in tissue homeostasis and behavior. Front. Immunol., 2021, Vol. 12, 629986. doi: 10.3389/fimmu.2021.629986.
- Le Friec G., Sheppard D., Whiteman P., Karsten C.M., Shamoun S.A., Laing A. The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat. Immunol., 2012, Vol. 13, no. 12, pp. 1213-1221.
- Li M., Guo W., Dong Y., Wang X., Dai D., Liu X., Wu Y., Li M., Zhang W., Zhou H., Zhang Z., Lin L., Kang Z., Yu T., Tian C., Qin R., Gui Y., Jiang F., Fan H., Heissmeyer V., Sarapultsev A., Wang L., Luo S., Hu D. Elevated exhaustion levels of NK and CD8+ T cells as indicators for progression and prognosis of COVID-19 disease. Front. Immunol., 2020, Vol. 11, 580237. doi: 10.3389/fimmu.2020.580237.
- Liszewski M.K., Atkinson J.P. Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections. Curr. Opin. Immunol., 2021, Vol. 72, pp. 126-134.
- Masselli E., Vaccarezza M., Carubbi C., Pozzi G., Presta V., Mirandola P., Vitale M. NK cells: A double edge sword against SARS-CoV-2. Adv. Biol. Regul., 2020, Vol. 77, 100737. doi: 10.1016/j.jbior.2020.100737.
- Mitsuyama Y., Yamakawa K., Kayano K., Maruyama M., Wada T., Fujimi S. Prolonged enhancement of cytotoxic T lymphocytes in the post-recovery state of severe COVID-19. J. Intensive Care, 2021, Vol. 9, 76. doi: 10.1186/s40560-021-00591-3.
- Persson B.D., John L., Rafie K., Strebl M., Frängsmyr L., Ballmann M.Z., Mindler K., Havenga M., Lemckert A., Stehle T., Carlson L.A., Arnberg N. Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46. Proc. Natl Acad. Sci. USA, 2021, Vol. 118, no. 3, e2020732118. doi: 10.1073/pnas.2020732118.
- Stein K.R., Gardner T.J., Hernandez R.E., Kraus T.A., Duty J.A., Ubarretxena-Belandia I., Moran T.M., Tortorella D. CD46 facilitates entry and dissemination of human cytomegalovirus. Nat. Commun., 2019, Vol. 10, no. 1, 2699. doi: 10.1038/s41467-019-10587-1.
- Verdecchia P., Cavallini C., Spanevello A., Angelim F. The pivotal link between ACE2 deficiency and SARS-cov-2 infection. Eur. J. Intern. Med., 2020, Vol. 76, pp. 14-20.
- Wu Y., Huang X., Sun J., Xie T., Lei Y., Muhammad J., Li X., Zeng X., Zhou F., Qin H., Shao L., Zhang Q. Clinical characteristics and immune injury mechanisms in 71 patients with COVID-19. mSphere, 2020, Vol. 5, no. 4, e00362-20. doi: 10.1128/mSphere.00362-20.