Eritrosit Süspansiyonlarının Depolanma Koşullarının T Hücre Canlılığı ve Proliferasyonu Üzerindeki Etkisi

Yıl 2023, , 205 - 212, 08.09.2023

Hakan Yılmaz , Salih Haldun Bal , Diğdem Yöyen Ermiş , Gözde Arslan , Fatma Dombaz Özbey , Levent Tufan Kumaş , Yasemin Heper , Barbaros Oral

https://doi.org/10.32708/uutfd.1313635

Öz

Önemli transfüzyon komplikasyonlardan biri olan transfüzyonla ilişkili immün düzenlenme (TRIM), allojeneik kan transfüzyonunun (AKT) alıcının immün sisteminde yol açtığı değişiklikler olarak tanımlanabilir. En çok suçlanan etken, kan bileşeni içindeki mononükleer (MNH) hücrelerdir. Bu nedenle çalışmamızda eritrosit süspansiyonları (ES) içindeki T hücreler (CD3+CD4+ ve CD3+CD8+) hedeflenmiş, depolama koşullarının etkisiyle canlılık, proliferasyon ve aktivasyon düzeylerindeki değişimler incelenmiştir. Bu amaçla, üç adet kan bağışçısından alınan tam kanlardan ES’ler elde edilmiştir. Her kan bileşeninden tam kan örneği (5. saat) ve ES örnekleri (0, 7, 14, 21, 42. gün) elde edilmiştir. Ayrıca bağışçıdan bağış öncesi EDTA’lı tüplere alınan iki adet örnek de çalışmaya katılmıştır. Analizler bu örneklerden ayrıştırılan MNH kullanılarak yapılmıştır. Canlılık analizleri doğrudan MNH’ler, proliferasyon ve aktivasyon analizleri MNH kültürleri aracılığıyla akan hücre ölçerde gerçekleştirilmiştir. Canlılık düzeylerinin depolama süresi ortalarında azalmaya başladığı, 42. gün ES örneklerinde hemen tamamen yok olduğu belirlenmiştir. T hücrelerin proliferasyon becerisi daha erken azalmış ve 21. gün ES örneklerinde kaybolmuştur. Aktivasyon belirteci düzeyleri MNH kültürünün sıfırıncı saatlerine göre 16 ve 72 saatlerde artış göstermiştir. Ayrıca bağışçıların yaşlarına göre de sonuçlarda belirgin farklılıklar gözlemlenmiştir. Sonuç olarak ES depolama süresi ve koşullarının etkisiyle ürün içindeki T lenfositlerin canlılığı ve proliferasyon becerileri azalmaktadır. Bu sonuçlar allojeneik T lenfositlerin TRIM gelişimiyle ilişkilerinin düşük olabileceğini; T lenfosit aktivasyon kapasitelerinin ES’den uzaklaştıklarında artmış göstermesi eritrositlerin baskılayıcı özellik gösterebildiğini; TRIM gelişiminde bağışçı ve hasta yaşı gibi demografik parametrelerin de rol oynayabileceğini düşündürmektedir.

Anahtar Kelimeler

Eritrosit süspansiyonu, canlılık, proliferasyon, immün düzenlenme, T lenfosit

The Effect of Storage Conditions of Erythrocyte Suspensions on T Cell Viability and Proliferation

Öz

Transfusion-related immunomodulation (TRIM) can be defined as changes in the immune system of the recipient caused by allogeneic blood transfusion (ABT). The most commonly blamed agent is mononuclear (MNC) cells in the blood component. Therefore, T cells (CD3+CD4+ and CD3+CD8+) in erythrocyte suspensions (ES) were targeted in our study. The effect of storage conditions on viability, proliferation, and activation levels were analysed. ESs were obtained from whole bloods donated from three donors. Whole blood sample (5th hour) and ES samples (0, 7, 14, 21, 42nd day) were achieved from each blood component. Two samples taken from donors in EDTA tubes before donation were also included in the study. MNCs were isolated from these samples and analyses were performed with these cells by flow-cytometer. T-cell viability disappeared in the 42nd-day ES samples, whereas proliferation capacity was lost in the 21st-day ES samples. Activation marker levels increased at 16 and 72 hours compared to 0 hours MNH culture. Also, distinct differences were observed among results according to the ages of the donors. In conclusion, the viability and proliferation capacity of T lymphocytes in the ES decreases with the effect of storage time and conditions. These results suggest that the relationship between allogeneic T lymphocytes and the development of TRIM may be low; the increased activation capacity of T lymphocytes when they are removed from ES suggests that erythrocytes may show suppressive properties; and demographic parameters such as donor and patient age may also play a role in the development of TRIM.

Anahtar Kelimeler

Erythrocyte suspension, viability, proliferation, immunomodulation, T lymphocyte

Kaynakça

• 1. Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973;5(1):253–9.
• 2. Gantt CL. Red blood cells for cancer patients. Lancet 1981;2(8242):363.
• 3. Mowbray JF, Gibbings C, Liddell H, et al. Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells. Lancet 1985;1(8435):941–3.
• 4. Peters WR, Fry RD, Fleshman JW, Kodner IJ. Multiple blood transfusions reduce the recurrence rate of Crohn’s disease. Dis Colon Rectum 1989;32(9):749–53.
• 5. Sloand E, Kumar P, Klein HG, Merritt S, Sacher R. Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection. Transfusion 1994;34(1):48–53.
• 6. Chang H, Hall GA, Geerts WH, et al. Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection. Vox Sang 2000;78(1):13–8.
• 7. Kneyber MCJ, Hersi MI, Twisk JWR, Markhorst DG, Plötz FB. Red blood cell transfusion in critically ill children is independently associated with increased mortality. Intensive Care Med 2007;33(8):1414–22.
• 8. Gauvin F, Spinella PC, Lacroix J, et al. Association between length of storage of transfused red blood cells and multiple organ dysfunction syndrome in pediatric intensive care patients. Transfusion 2010;50(9):1902–13.
• 9. Kneyber MCJ, Grotenhuis F, Berger RFM, et al. Transfusion of leukocyte-depleted RBCs is independently associated with increased morbidity after pediatric cardiac surgery. Pediatr Crit Care Med 2013;14(3):298–305.
• 10. Zhu X, Yu B, You P, et al. Ubiquitin released in the plasma of whole blood during storage promotes mRNA expression of Th2 cytokines and Th2-inducing transcription factors. Transfus Apher Sci 2012;47(3):305–11.
• 11. Baumgartner JM, Silliman CC, Moore EE, Banerjee A, McCarter MD. Stored red blood cell transfusion induces regulatory T cells. J Am Coll Surg 2009;208(1):110–9.
• 12. Chen G, Zhang F jiang, Gong M, Yan M. Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients. J Zhejiang Univ Sci B 2007;8(8):560–5.
• 13. Ghio M, Contini P, Negrini S, et al. Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion: role of transforming growth factor-β(1), soluble Fas ligand, and soluble Class I human leukocyte antigen. Transfusion 2011;51(7):1567–73.
• 14. Muszynski JA, Bale J, Nateri J, et al. Supernatants from stored red blood cell (RBC) units, but not RBC-derived microvesicles, suppress monocyte function in vitro. Transfusion 2015;55(8):1937–45.
• 15. Long K, Meier C, Ward M, et al. Immunologic profiles of red blood cells using in vitro models of transfusion. J Surg Res 2013;184(1):567–71.
• 16. Bal SH, Oral HB. Transfusion-related immunomodulation. Turkish J Immunol 2016;4(3):37–46.
• 17. Nascimento JEA do, Zampieri-Filho JP, Bordin JO. Implications of perioperative allogeneic red blood cell transfusion on the immune-inflammatory response. Hematol Transfus Cell Ther 2021;43(1):58–64.
• 18. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): An update. Blood Rev 2007;21(6):327–48.
• 19. Cholette JM, Pietropaoli AP, Henrichs KF, et al. Longer RBC Storage Duration Is Associated With Increased Postoperative Infections in Pediatric Cardiac Surgery. Pediatr Crit Care Med 2015;16(3):227–35.
• 20. Rodieck W, Hallensleben M, Robert J, et al. Impact of perioperative blood transfusions on postoperative renal function and survival after resection of colorectal liver metastases. World J Surg Oncol 2022;20(1):100.
• 21. Bal SH, Heper Y, Kumaş LT, et al. Effect of storage period of red blood cell suspensions on helper T-cell subpopulations. Blood Transfus 2018;16(3):262–72.
• 22. Bal SH, Kumaş LT, Heper Y, et al. Impact of Storage Period on CD4 + /CD8 + T Lymphocyte Ratio in Erythrocyte Suspensions Eritrosit Süspansiyonlarında Depolanma Sürecinin CD4 + /CD8 + T Lenfositleri Oranı Üzerine Etkisi. Turk J Immunol 2020;8(2):44–9.
• 23. Belloni P, Meschini R, Palitti F. Effects of storage conditions of human whole blood on the viability of lymphocytes. Int J Radiat Biol 2008;84(7):613–9.
• 24. Jerram A, Guy TV, Beutler L, et al. Effects of storage time and temperature on highly multiparametric flow analysis of peripheral blood samples; implications for clinical trial samples. Biosci Rep 2021;41(2).
• 25. Shen G, Krienke S, Schiller P, et al. Microvesicles released by apoptotic human neutrophils suppress proliferation and IL-2/IL-2 receptor expression of resting T helper cells. Eur J Immunol 2017;47(5):900–10.
• 26. Hodge GL, Hodge SJ, Nairn J, et al. Poststorage leuko-depleted plasma inhibits T-cell proliferation and Th1 response in vitro: characterization of TGFbeta-1 as an important immunomodulatory component in stored blood. Transplantation 2005;80(1):95–101.
• 27. Bernard A, Meier C, Ward M, et al. Packed red blood cells suppress T-cell proliferation through a process involving cell-cell contact. J Trauma - Inj Infect Crit Care 2010;69(2):320–7.
• 28. Long K, Meier C, Bernard A, et al. T-cell suppression by red blood cells is dependent on intact cells and is a consequence of blood bank processing. Transfusion 2014;54(5):1340–7.
• 29. Chang H, Voralia M, Meenakshi B, Sher GD, Branch DR. Irreversible loss of donor blood leucocyte activation may explain a paucity of transfusion-associated graft-versus-host disease from stored blood. Br J Haematol 2000;111(1):146–56.
• 30. Goel R, Johnson DJ, Scott AV, et al. Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients. Transfusion 2016;56(7):1690–8.
• 31. Rapido F, Brittenham GM, Bandyopadhyay S, et al. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest 2017;127(1):375–82.
• 32. Atzil S, Arad M, Glasner A, et al. Blood transfusion promotes cancer progression: a critical role for aged erythrocytes. Anesthesiology 2008;109(6):989–97.
• 33. Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood 2010;115(21):4284–92.
• 34. Gerner MC, Bileck A, Janker L, et al. Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways. J Biol Chem 2021;296:100487.