Evaluation of T-cell Function after Blood Transfusion in Patients Undergoing Coronary Artery Bypass Grafting
-
Nasim Golafshani
,
Narges Golafshani
,
Ali Reza Mohseni
,
Mahboubah Mohseni
,
Ahmad Najafi
,
Shervin Ziabakhsh-Tabari
,
Hossein Asgarian-Omran
,
Mohsen Tehrani
,
Aliakbar Pourfathollah
Abstract
Blood transfusion is associated with increased mortality and morbidity. This study aimed to determine the effect of blood transfusion on T-helper 1 (TH1), TH2, and TH17 function in patients undergoing coronary artery bypass grafting (CABG).
Two blood samples were obtained from patients undergoing CABG, before and 14 days after surgery. Production of interleukin (IL)-2, IL-4, interferon (IFN)-γ, IL-17A, and IL-10 by CD4+ T cells was measured using enzyme-linked immunosorbent assay (ELISA). mRNA expression of T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA3), RAR-related orphan receptor-γ (ROR-γt), signal transducer and activator of transcription 3 (STAT3), STAT4, and STAT6 were measured using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
mRNA expression of T-bet and STAT4 showed a significant decrease after blood transfusion. However, the concentration of IFN-γ in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of GATA3 and STAT6 showed a significant decrease after blood transfusion. However, the concentration of IL-4 in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of ROR-γt showed no significant decrease after blood transfusion; however, the expression of STAT3 and the concentration of IL-4 in the culture supernatant did significantly decrease following blood transfusion. IL-10 production increased significantly postoperatively.
Decreased TH1, TH2, and TH17 signaling pathway activity and increased IL-10 concentration indicate an immunomodulatory effect on the immune system after blood transfusion.
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10. Wang X, Fan H, Wang Y, Yin X, Liu G, Gao C, et al. Elevated peripheral T helper cells are associated with atrial fibrillation in patients with rheumatoid arthritis. Front Immunol. 2021;12:744254.
11. Gaudriot B, Uhel F, Gregoire M, Gacouin A, Biedermann S, Roisne A, et al. Immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation. Shock. 2015;44(3):228-33.
12. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-8.
13. Leal-Noval SR, Muñoz-Gómez M, Arellano V, Adsuar A, Jiménez-Sánchez M, Corcia Y, et al. Influence of red blood cell transfusion on CD4+ T-helper cells immune response in patients undergoing cardiac surgery. J Surgical Res. 2010;164(1):43-9.
14. Tárnok A, Schneider P. Induction of transient immune suppression and TH1/TH2 disbalance by pediatric cardiac surgery with cardiopulmonary bypass. Clin Applied Immunol Rev. 2001;1(5):291-313.
15. Paruk F, Chausse JM. Monitoring the post surgery inflammatory host response. J Emergency Critical Care Med. 2019;3.
16. Rogozynski NP, Dixon B. The TH1/TH2 paradigm: A misrepresentation of helper T cell plasticity. Immunol Lett. 2024 Aug;268:106870. TH1TH2.
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18. Khan AI, Patidar GK, Lakshmy R, Makhija N, Talwar S, Hazarika A. Effect of leukoreduction on transfusion‐related immunomodulation in patients undergoing cardiac surgery. Transfusion Med. 2020;30(6):497-504.
19. Martinez MJ, Schwingshackl A, Romero T, Roach GD, Belperio JA, Federman MD. Cell saver blood transfusions may be associated with a decrease in inflammation and improved outcome measures in pediatric cardiac surgery patients. Perfusion. 2023;38(4):717-24.
20. Valizadeh S, Chegini A, Behnaz F, Pourfatollah AA, Karbalaeifar R. Unraveling the Impact of Blood Transfusion on Transcription Factors Regulating T Helper 1, 2, 17 and Regulatory T cells. Iranian J Allergy Asthma Immunol. 2024:1-8.
21. Li C, Zhu D, Zhao Y, Guo Q, Sun W, Li L, et al. Dendritic cells therapy with cytokine-induced killer cells and activated cytotoxic T cells attenuated TH2 bias immune response. Immunol Invest. 2020;49(5):522-34.
22. Ackerman RS, Luddy KA, Icard BE, Fernández JP, Gatenby RA, Muncey AR. The effects of anesthetics and perioperative medications on immune function: a narrative review. Anesth Analg. 2021;133(3):676-89.
23. Spinella PC, Sniecinski RM, Trachtenberg F, Inglis HC, Ranganathan G, Heitman JW, et al. Effects of blood storage age on immune, coagulation, and nitric oxide parameters in transfused patients undergoing cardiac surgery. Transfusion. 2019;59(4):1209-22.
24. Saracevic A, Medved I, VLAH SH, Kozmar A, Bilic-Zulle L, Simundic A-M. The association of systemic inflammatory markers with indicators of stress and cardiac necrosis in patients undergoing aortic valve replacement and revascularization surgeries. Physiol Res. 2020;69(2):261.
25. Najafi S, Ghanavat M, Shahrabi S, Gatavizadeh Z, Saki N. The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate. Cell Biol Int. 2021;45(5):900-12.
26. Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery: Developed by the task force for cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology (ESC) Endorsed by the European Society of Anaesthesiology and Intensive Care (ESAIC). Eur Heart J. 2022;43(39):3826-924.
27. Mincheff M, Meryman H. Blood transfusion, blood storage and immunomodulation. Immunol Invest. 1995;24(1-2):303-9.
28. Morikawa Y, Furotani M, Matsuura N, Kakudo K. The Role of Antigen-Presenting Cells in the Regulation of Delayed-Type Hypersensitivity: II. Epidermal Langerhans' Cells and Peritoneal Exudate Macrophages. Cell Immunol. 1993;152(1):200-10.
29. Fredens K, Dybdahl H, Dahl R, Baandrup U. Extracellular deposit of the cationic proteins ECP and EPX in tissue infiltrations of eosinophils related to tissue damage. Apmis. 1988;96(7‐12):711-9.
30. Nielsen H, Reimert C, Pedersen A, Brünner N, Edvardsen L, Dybkjaer E, et al. Time‐dependent, spontaneous release of white cell‐and platelet‐derived bioactive substances from stored human blood. Transfusion. 1996;36(11‐12):960-5.
31. Feola M, Simoni J, Tran R, Lox CD, Canizaro PC. Toxic factors in the red blood cell membrane. J Trauma. 1989;29(8):1065-75.
32. Grover GJ, Loegering DJ. Effect of splenic sequestration of erythrocytes on splenic clearance function and susceptibility to septic peritonitis. Infec Immun. 1982;36(1):96-102.
2. Ming Y, Liu J, Zhang F, Chen C, Zhou L, Du L, et al. Transfusion of red blood cells, fresh frozen plasma, or platelets is associated with mortality and infection after cardiac surgery in a dose-dependent manner. Anesth Analg. 2020;130(2):488-97.
3. Ad N, Massimiano PS, Rongione AJ, Taylor B, Schena S, Alejo D, et al. Number and type of blood products are negatively associated with outcomes after cardiac surgery. Ann Thorac Surg. 2022;113(3):748-56.
4. Brevig J, McDonald J, Zelinka ES, Gallagher T, Jin R, Grunkemeier GL. Blood transfusion reduction in cardiac surgery: multidisciplinary approach at a community hospital. Ann Thorac Surg. 2009;87(2):532-9.
5. Irving AH, Harris A, Petrie D, Higgins A, Smith J, McQuilten ZK. Impact of patient blood management guidelines on blood transfusions and patient outcomes during cardiac surgery. J Thorac Cardiovasc Surg. 2020;160(2):437-45. e20.
6. Remy KE, Hall MW, Cholette J, Juffermans NP, Nicol K, Doctor A, et al. Mechanisms of red blood cell transfusion‐related immunomodulation. Transfusion. 2018;58(3):804-15.
7. Refaai MA, Blumberg N. Transfusion immunomodulation from a clinical perspective: an update. Expert Rev Hematol. 2013;6(6):653-63.
8. Yazdanbakhsh K, Bao W, Zhong H. Immunoregulatory effects of stored red blood cells. Hematology Am Soc Hematol Educ Program. 2011;2011(1):466-9.
9. Franke A, Lante W, Kurig E, Zöller LG, Weinhold C, Markewitz A. Hyporesponsiveness of T cell subsets after cardiac surgery: a product of altered cell function or merely a result of absolute cell count changes in peripheral blood? Eur J Cardiothorac Surg. 2006;30(1):64-71.
10. Wang X, Fan H, Wang Y, Yin X, Liu G, Gao C, et al. Elevated peripheral T helper cells are associated with atrial fibrillation in patients with rheumatoid arthritis. Front Immunol. 2021;12:744254.
11. Gaudriot B, Uhel F, Gregoire M, Gacouin A, Biedermann S, Roisne A, et al. Immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation. Shock. 2015;44(3):228-33.
12. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-8.
13. Leal-Noval SR, Muñoz-Gómez M, Arellano V, Adsuar A, Jiménez-Sánchez M, Corcia Y, et al. Influence of red blood cell transfusion on CD4+ T-helper cells immune response in patients undergoing cardiac surgery. J Surgical Res. 2010;164(1):43-9.
14. Tárnok A, Schneider P. Induction of transient immune suppression and TH1/TH2 disbalance by pediatric cardiac surgery with cardiopulmonary bypass. Clin Applied Immunol Rev. 2001;1(5):291-313.
15. Paruk F, Chausse JM. Monitoring the post surgery inflammatory host response. J Emergency Critical Care Med. 2019;3.
16. Rogozynski NP, Dixon B. The TH1/TH2 paradigm: A misrepresentation of helper T cell plasticity. Immunol Lett. 2024 Aug;268:106870. TH1TH2.
17. Squiccimarro E, Labriola C, Malvindi PG, Margari V, Guida P, Visicchio G, et al. Prevalence and clinical impact of systemic inflammatory reaction after cardiac surgery. J Cardiothorac Vasc Anesth. 2019;33(6):1682-90.
18. Khan AI, Patidar GK, Lakshmy R, Makhija N, Talwar S, Hazarika A. Effect of leukoreduction on transfusion‐related immunomodulation in patients undergoing cardiac surgery. Transfusion Med. 2020;30(6):497-504.
19. Martinez MJ, Schwingshackl A, Romero T, Roach GD, Belperio JA, Federman MD. Cell saver blood transfusions may be associated with a decrease in inflammation and improved outcome measures in pediatric cardiac surgery patients. Perfusion. 2023;38(4):717-24.
20. Valizadeh S, Chegini A, Behnaz F, Pourfatollah AA, Karbalaeifar R. Unraveling the Impact of Blood Transfusion on Transcription Factors Regulating T Helper 1, 2, 17 and Regulatory T cells. Iranian J Allergy Asthma Immunol. 2024:1-8.
21. Li C, Zhu D, Zhao Y, Guo Q, Sun W, Li L, et al. Dendritic cells therapy with cytokine-induced killer cells and activated cytotoxic T cells attenuated TH2 bias immune response. Immunol Invest. 2020;49(5):522-34.
22. Ackerman RS, Luddy KA, Icard BE, Fernández JP, Gatenby RA, Muncey AR. The effects of anesthetics and perioperative medications on immune function: a narrative review. Anesth Analg. 2021;133(3):676-89.
23. Spinella PC, Sniecinski RM, Trachtenberg F, Inglis HC, Ranganathan G, Heitman JW, et al. Effects of blood storage age on immune, coagulation, and nitric oxide parameters in transfused patients undergoing cardiac surgery. Transfusion. 2019;59(4):1209-22.
24. Saracevic A, Medved I, VLAH SH, Kozmar A, Bilic-Zulle L, Simundic A-M. The association of systemic inflammatory markers with indicators of stress and cardiac necrosis in patients undergoing aortic valve replacement and revascularization surgeries. Physiol Res. 2020;69(2):261.
25. Najafi S, Ghanavat M, Shahrabi S, Gatavizadeh Z, Saki N. The effect of inflammatory factors and their inhibitors on the hematopoietic stem cells fate. Cell Biol Int. 2021;45(5):900-12.
26. Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery: Developed by the task force for cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology (ESC) Endorsed by the European Society of Anaesthesiology and Intensive Care (ESAIC). Eur Heart J. 2022;43(39):3826-924.
27. Mincheff M, Meryman H. Blood transfusion, blood storage and immunomodulation. Immunol Invest. 1995;24(1-2):303-9.
28. Morikawa Y, Furotani M, Matsuura N, Kakudo K. The Role of Antigen-Presenting Cells in the Regulation of Delayed-Type Hypersensitivity: II. Epidermal Langerhans' Cells and Peritoneal Exudate Macrophages. Cell Immunol. 1993;152(1):200-10.
29. Fredens K, Dybdahl H, Dahl R, Baandrup U. Extracellular deposit of the cationic proteins ECP and EPX in tissue infiltrations of eosinophils related to tissue damage. Apmis. 1988;96(7‐12):711-9.
30. Nielsen H, Reimert C, Pedersen A, Brünner N, Edvardsen L, Dybkjaer E, et al. Time‐dependent, spontaneous release of white cell‐and platelet‐derived bioactive substances from stored human blood. Transfusion. 1996;36(11‐12):960-5.
31. Feola M, Simoni J, Tran R, Lox CD, Canizaro PC. Toxic factors in the red blood cell membrane. J Trauma. 1989;29(8):1065-75.
32. Grover GJ, Loegering DJ. Effect of splenic sequestration of erythrocytes on splenic clearance function and susceptibility to septic peritonitis. Infec Immun. 1982;36(1):96-102.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Blood transfusion Coronary artery bypass Cytokines Immunomodulation T-lymphocytes TH1 cells TH2 cells TH1 TH2 | ||
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How to Cite
1.
Golafshani N, Golafshani N, Mohseni AR, Mohseni M, Najafi A, Ziabakhsh-Tabari S, Asgarian-Omran H, Tehrani M, Pourfathollah A. Evaluation of T-cell Function after Blood Transfusion in Patients Undergoing Coronary Artery Bypass Grafting. Iran J Allergy Asthma Immunol. 2024;:1-6.
