Original Article
  

Unraveling the Impact of Blood Transfusion on Transcription Factors Regulating T Helper 1, 2, 17 and Regulatory T cells

Abstract

T helper 1 (TH1) and TH2 lymphocytes are the most important components of the immune system affected by blood transfusion. This study aimed`` to evaluate the effect of blood transfusion on gene expression of transcription factors related to the development of TH1, TH2, TH17 and regulatory T cells (Tregs).
In this cross-sectional study, 20 patients diagnosed with abdominal aortic aneurysms requiring surgical repair were studied from January 2018 to August 2020. We utilized real-time PCR to evaluate the expression of transcription factor genes associated with TH1, TH2, TH17, and Treg, namely T-box-expressed-in-T-cells (T-bet), GATA-binding protein 3 (GATA-3), retinoid-related orphan receptor (RORγt), and fork head box protein 3 (Foxp3), respectively. The sampling occurred before anesthesia, 24- and 72 hours post-transfusion, and at the time of discharge.
The results showed that the T-bet gene expression, compared to the time before transfusion, was significantly decreased 24 hours after blood transfusion and upon discharge while GATA3 genes exhibited a significant reduction both 24 and 72 hours after the transfusion, as compared to the pre-transfusion levels and the time of patient discharge. The Foxp3 gene demonstrated an increase at all study stages, with a notable surge, particularly 72 hours after red blood cell (RBC) transfusion. Conversely, the expression of RORγt gene, consistently decreased throughout all stages of the study.
RBC transfusion in abdominal aortic aneurysm patients altered the balance of transcription gene expression of TH1, TH2, TH17, and Treg cells.

1. Cronenwett J, Murphy T, Zelenock G, Whitehouse Jr W, Lindenauer S, Graham L, et al. Actuarial analysis of variables associated with rupture of small abdominal aortic aneurysms. Surgery. 1985;98(3):472.
2. Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. The Lancet. 2005;365(9470):1577-89.
3. Ilyas S, Shaida N, Thakor AS, Winterbottom A, Cousins C. Endovascular aneurysm repair (EVAR) follow-up imaging: the assessment and treatment of common postoperative complications. Clinical Radiology. 2015;70(2):183-96.
4. Haynes SL, Wong JC, Torella F, Dalrymple K, Pilsworth L, McCollum CN. The influence of homologous blood transfusion on immunity and clinical outcome in aortic surgery. European Journal of Vascular and Endovascular Surgery. 2001 Sep 1;22(3):244-50. PMID: 11506518 DOI: 10.1053/ejvs.2001.1408
5. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood reviews. 2007;21(6):327-48.
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. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood reviews. 2007 Nov 1;21(6):327-48. PMID: 17804128 DOI: 10.1016/j.blre.2007.07.003
8. 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. Journal of Surgical Research. 2010;164(1):43-99.
9. Englesbe MJ, Pelletier SJ, Diehl KM, Sung RS, Wahl WL, Punch J, et al. Transfusions in surgical patients. J Am Coll Surg. 2005;200(2):249-54
10. Kumar BV, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity. 2018;48(2):202-13.
11. Luckheeram RV, Zhou R, Verma AD, Xia B. CD4+ T cells: differentiation and functions. Clin Dev Immunol. 2012;2012:925135.
12. Thieu VT, Yu Q, Chang H-C, Yeh N, Nguyen ET, Sehra S, et al. Stat4 is required for T-bet to promote IL-12-dependent Th1 fate determination. Immunity. 2008;29(5):679.
13. Paul WE, Zhu J. How are T H 2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225-35.
14. Zhu J, Paul WE. Heterogeneity and plasticity of T helper cells. Cell research. 2010;20(1):4-12.
15. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor FOXP3. Science. 2003;299:1057–61.
16. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100(6):655-6969.
17. Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat Rev Immunol. 2012;12(3):191–200.
18. Kitamura N, Kaminuma O, Mori A, Hashimoto T, Kitamura F, Miyagishi M, et al.Correlation between mRNA expression of Th1/Th2 cytokines and their specific transcription factors in human helper T-cell clones. Immunol Cell Biol. 2005;83(5):536–41.
19. Duggan E, Caraher E, Gately K, O’Dwyer M, McGovern E, Kelleher D, et al. Tumor necrosis factor-alpha and interleukin-10 gene expression in peripheral blood mononuclear cells after cardiac surgery. Crit Care Med. 2006;34(8):2134–9.
20. Steinman L. A brief history of Th 17, the first major revision in the Th 1/Th 2 hypothesis of T cell–mediated tissue damage. Nature medicine. 2007;13(2):139-45.
21. Dong C. TH 17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008;8(5):337-48.
22. Wong ML, Medrano JF. Real-time PCR for mRNA quantitation. Biotechniques. 2005;39(1):75-85.
23. Behnaz F, Karbalaeifar R, Chegini A, Mohseni G, Valizadeh S. Effect of dexmedetomidine on transcription factors and inflammatory cytokines in elective aortic aneurysm repair surgery. Journal of Cellular and Molecular Anesthesia. 2020;5(3).
24. Wei L, Meng QG, Bi ZG. Result of a randomized clinical trial comparing different types of anesthesia on the immune function of patients with osteosarcoma undergoing radical resection. Panminerva Med 2013;55(6):211-6.
25. Liu J, Dong W, Wang T, Liu L, Zhan L, Shi Y, Han J. Effects of etomidate and propofol on immune function in patients with lung adenocarcinoma. American journal of translational research. 2016;8(12):5748.
26. Torrance HD, Brohi K, Pearse RM, Mein CA, Wozniak E, Prowle JR, et al. Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma. Ann Surg. 2015;261(4):751-9.
27. Zhu M, Zhu Z, Yang J, Hu K, Li Y. Impact of perioperative blood transfusion on gene expression biomarkers in patients with gastrointestinal cancer. Transfus Apher Sci. 2018;57(5):656-60.
28. Fragkou PC, Torrance HD, Pearse RM, Ackland GL, Prowle JR, Owen HC, et al. Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study. Critical Care. 2014;18(5):541.
29. Qian Y, Tang Q, Wang Z, Sun J, Li Q. Effect of allograft blood transfusion on Th1/Th2 balance and T cell surface antigens expression. Clin Chim Acta. 2006;366(1-2):361.
Files
IssueVol 23 No 1 (2024) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v23i1.14958
Keywords
Abdominal aortic aneurysm Blood transfusion Helper-inducer T-Lymphocyte Regulatory T-Cells T helper 1 cells T helper 2 cells T helper 17 cells Transcription factors
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Valizadeh S, Chegini A, Behnaz F, Pourfatollah A, samiee S, Karbalaeifar R. Unraveling the Impact of Blood Transfusion on Transcription Factors Regulating T Helper 1, 2, 17 and Regulatory T cells. Iran J Allergy Asthma Immunol. 2024;23(1):107-114.