Soluble forms of programmable cell death receptor sPD-L and ligand sPD-L1, as well as some biochemical and hematological indicators in the blood of COVID-19 diseased
- Authors: Kushlinskii N.E.1, Babkina I.V.1, Gerstein E.S.1, Lyubimova N.V.1, Timofeev Y.S.1, Korotkova E.A.1, Zubrikhina G.N.1, Davydova T.V.1, Somonova O.V.1, Stilidi I.S.1
-
Affiliations:
- N.N. Blokhin National Medical Research Center of Oncology
- Issue: Vol 20, No 2 (2022)
- Pages: 26-31
- Section: Articles
- URL: https://journals.eco-vector.com/1728-2918/article/view/113576
- DOI: https://doi.org/10.29296/24999490-2022-02-04
- ID: 113576
Cite item
Abstract
Introduction. The main reason for the severity of COVID-19 and the death of patients is the «cytokine storm» - a strong inflammatory response caused by SARS-CoV-2. Macrophages, immune cells that help eliminate pathogens and repair damaged tissues, play a key role in the expression of inflammatory mediators. In addition to known cytokines, macrophages express the PD-L1 protein, a ligand of the PD1 apoptosis receptor. The aim of the study was to comparatively analyze the levels of soluble forms of the programmed cell death receptor (sPD-1) and its ligand (sPD-L1), as well as biochemical and hematological parameters in the blood of patients who underwent COVID-19. Material and methods. We carried out sPD-1 and sPD-L1 enzyme immunoassay and biochemical studies in 72 employees of the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation who have undergone COVID-19. The control group consisted of 57 healthy donors. The fact of the disease was confirmed by the presence of antibodies to class G immunoglobulins (SARS-Cov-2 IgG) in the blood serum using the ELISA test system Antigma-G (Generium, Russia). The concentrations of sPD-1 and sPD-L1 in blood serum were studied using the Human sPD-L1 ELISA kit and Human sPD-1 ELISA kit (Affimetrix, eBioscience, USA). The levels of iron, transferrin and ferritin were determined on an automatic analyzer Cobas (Roche). Complete blood count was performed on an automatic Sysmex XE-2100 analyzer (Japan). Results. In the serum of those who underwent COVID-19 (30-50 days after the onset of the first symptoms), there was a significant decrease in sPD-L1 levels and a change in the correlation between the components of the sPD-1 / sPD-L1 system. A statistically significant direct relationship was found between the concentrations of soluble forms of the sPD-1 receptor and its ligand sPD-L1 with the levels of iron, hemoglobin and the number of erythrocytes, as well as between sPD-L1 and ferritin. No relationship was found between sPD-1 and sPD-L1 levels and erythrocyte counts (MCV, MCH, RDW-SD). Conclusion. The results obtained expand the understanding of the role of sPD-1 and sPD-L1 in persons who have undergone COVID-19, demonstrate the relationship between the processes of apoptosis, some biochemical and hematological parameters of blood serum, and are the basis for further research.
Keywords
Full Text
![Restricted Access](https://journals.eco-vector.com/lib/pkp/templates/images/icons/text_lock.png)
About the authors
Nikolay Evgen’evich Kushlinskii
N.N. Blokhin National Medical Research Center of Oncology
Author for correspondence.
Email: kne3108@gmail.com
Academician of RAS, Doctor of Medical Sciences, Professor, head of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Irina Valentinovna Babkina
N.N. Blokhin National Medical Research Center of Oncology
Email: docbabkina@rambler.ru
Doctor of Medical Sciences, doctor of clinical laboratory diagnostics of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Elena Sergeevna Gerstein
N.N. Blokhin National Medical Research Center of Oncology
Email: esgershtein@gmail.com
Doctor of Biological Sciences, Professor, leading researcher of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Nina Vasilyevna Lyubimova
N.N. Blokhin National Medical Research Center of Oncology
Email: biochimia@yandex.ru
Doctor of Biological Sciences, chief scientific consultant of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Yuriy Sergeevich Timofeev
N.N. Blokhin National Medical Research Center of Oncology
Email: timofeev_lab@mail.ru
Candidate of Medical Sciences, doctor of clinical laboratory diagnostics of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Ekaterina Andreevna Korotkova
N.N. Blokhin National Medical Research Center of Oncology
Email: katinka-kor@yandex.ru
Candidate of Biological Sciences, senior researcher of the laboratory of clinical biochemistry Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Galina Nikolaevna Zubrikhina
N.N. Blokhin National Medical Research Center of Oncology
Email: zubrlab@list.ru
Doctor of Medical Sciences, scientific consultant of the clinical and diagnostic laboratory Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Tatiana Vladimirovna Davydova
N.N. Blokhin National Medical Research Center of Oncology
Email: davydova.tata@mail.ru
Candidate of Biological Sciences, head of the clinical and diagnostic laboratory Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Oksana Vasyl’evna Somonova
N.N. Blokhin National Medical Research Center of Oncology
Email: somonova@mail.ru
Doctor of Medical Sciences, leading researcher of the clinical and diagnostic laboratory Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
Ivan Sokratovich Stilidi
N.N. Blokhin National Medical Research Center of Oncology
Email: info@ronc.ru
Academician of RAS, Doctor of Medical Sciences, Professor, Director Kashirskoe shosse, 24, Moscow, 115522, Russian Federation
References
- Gong J., Dong H., Xia S.Q., Huang Y., Wang D., Zhao Y., Liu W.H., Tu S.H., Zhang M.M., Wang Q., Lu F.E. Correlation analysis between disease severity and inflammation-related parameters in patients with COVID-19: a retrospective study. BMC Infect. Dis. 2020; 20 (1): 963. https://doi.org/10.1186/s12879-020-05681-5.
- Mehta P., McAuley D.F., Brown M., Sanche E., Tattersall R.S., Manson J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395 (10229): 1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0.
- Merad M., Martin J.C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat. Rev. Immunol. 2020; 20 (7): 448. https://doi.org/10.1038/s41577-020-0353-y
- Recalcati S., Locati M., Marini A., Santambrogio P., Zaninotto F.Differential regulation of iron homeostasis during human macrophage polarized activation. Eur. J. Immunol. 2010; 40 (3): 824-35. https://doi.org/0.1002/eji.200939889.
- Wei S.C., Levine J.H., Cogdill A.P., Zhao Y., Anang N.A.S., Andrews M.C. Sharma P., Wang J., Wargo J.A., Pe'er D., Allison J.P. Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade. Cell. 2017; 170 (6): 1120-33. e17. https://doi.org/10.10Wj.cell.2017.07.024.
- Rowe J.H., Johanns T.M., Ertelt J.M., Way S.S. PDL-1 blockade impedes T cell expansion and protective immunity primed by attenuated Listeria monocytogenes. J. Immunol. 2008; 180 (11): 7553-7. https://doi.org/10.4049/jimmunol.180.11.7553.
- Кушлинский Н.Е., Фридман М.В., Морозов А.А., Герштейн Е.С., Кадагидзе З.Г., Матвеев В.Б. Современные подходы к иммунотерапии рака почки. Онкоурология. 2018; 14 (2): 54-7. https://doi.org/10.17650/1726-9776-2018-14-2-54-67.
- Kyriazopoulou E., Giamarellos-Bourboulis E.J. Monitoring immunomodulation in patients with sepsis. Expert Rev. Mol. Diagn. 2021; 21 (1): 17-29. https://doi.org/10.1080/14737159.2020.1851199.
- Bryant-Hudson K.M., Carr D.J. PD-L1-expressing dendritic cells contribute to viral resistance during acute HSV-1 infection. Clin. Dev. Immunol. 2012; 2012: 924619. https://doi.org/10.1155/2012/924619.
- Jubel J.M., Barbati Z.R., Burger C., Wirtz D.C., Schildberg F.A. The Role of PD-1 in Acute and Chronic Infection. Front Immunol. 2020; 11: 487. https://doi.org/10.3389/fimmu.2020.00487.
- Schönrich G., Martin J., Raftery M.J. The PD-1/PD-L1 Axis and Virus Infections: A Delicate Balance. Front Cell Infect. Microbiol. 2019; 9: 207. https://doi.org/10.3389/fcimb.2019.00207.
- Yekedüz E., Dursun B., Aydin G.Q., Yazgan S.C., Öztürk H.H., Azap A., Utkan G., Ürün Y. Clinical course of COVID-19 infection in elderly patient with melanoma on nivolumab. J. Oncol. Pharm. Pract. 2020; 26 (5): 1289-94. https://doi.org/10.1177/1078155220924084.
- Ahmed H., Patel K., Greenwood D.C., Halpin S., Lewthwaite P., Salawu A., Eyre L., Breen A., O'Connor R., Jones A., Sivan M. Long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome coronavirus (MERS) outbreaks after hospitalisation or ICU admission: a systematic review and meta-analysis. J. Rehabil. Med. 2020; 52 (5): jrm00063. https://doi.org/10.2340/16501977-2694.
- Garg P., Arora U., Kumar A., Wig N. The "Post-COVID" syndrome: how deep is the damage? J. Med. Virol. 2021; 93 (2): 673-4. https://doi.org/10.1002/jmv.26465.
- Halpin S., O'Connor R., Sivan M. Long COVID and chronic COVID syndromes. J. Med. Virol. 2021; 93 (1): 1242-3. https://doi.org/10.1002/jmv.26587.
- Мещерякова Л.М., Левина А.А., Цыбульская М.М., Соколова Т.В. Основные механизмы регуляции обмена железа и их клиническое значение. Онкогематология. 2014; 3: 67-71. https://doi.org/10.17650/1818-8346-2014-9-3-67-71.
- Wang C., Deng R., Gou L., Fu Z., Zhang X., Shao F., Wang G., Fu W., Xiao J., Ding X., Li T., Xiao X., Chengbin Li C. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann. Transl. Med. 2020; 8 (9): 593. https://doi.org/10.21037/atm-20-3391.
Supplementary files
![](/img/style/loading.gif)