The Roles of Immune Molecules in the Acute Post-Transplant Period
Year 2024,
, 634 - 641, 30.09.2024
Aslı Özkızılcık Koçyiğit
,
Melek Pehlivan
,
Tülay Kılıçaslan Ayna
,
Mustafa Soyöz
,
Erhan Tatar
,
Mehmet Tanrısev
,
İsmail Sert
,
Zeki Soypacacı
,
Cem Tuğmen
,
İbrahim Pirim
Abstract
Purpose: Renal transplantation is a therapeutic choice that enhances the quality of life for patients suffering from end-stage renal failure. The objective of this study was to ascertain the alterations in the levels of immune molecules following transplantation and to examine the correlation between these changes and the medical records of the patients.
Materials and Methods: The gene expression of an immune molecule panel (FOXP3, TNF-α, IFN-γ, IL-18, IL-6, IL-17a, IL-12a, IL-2, IL-10, and TGF-β) in peripheral blood specimens of 30 kidney transplant patients was determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method with SYBR Green Dye. The serum proteins were quantified using Enzyme-Linked ImmunoSorbent Assay (ELISA).
Results: TGF-β exhibited the most significant alteration in gene expression levels compared to the levels before transplanting (p<0.05). A strong association was seen between the change in IFN-γ levels and the estimated glomerular filtration rate (eGFR) values of the patients (p<0.05).
Conclusion: The cytokine expression alterations may provide information on patients’ clinical condition. Individualized immune scanning after transplantations may contribute to personalized treatment of each patient. The communication between the laboratory and the clinics is important for the accurate consultation of the patients.
Ethical Statement
In compliance with the Declaration of Helsinki, Izmir Katip Celebi University Non-Interventional Clinical Research Ethics Committee approved the study (Decision No: 633, 13.02.2020).
Supporting Institution
Izmir Katip Celebi University
Project Number
2019-GAP-TIPF-0006 and 2020-TDR-SABE-011
Thanks
We express our gratitude to the staff members of the organ transplantation units in all participating hospitals for their involvement in this project. Furthermore, we express thanks to the hardworking team of the tissue typing laboratory.
References
- Turkish Nephrology Coordination [Internet]. Formula and Calculations. [Accessed date: 11 November 2021]. Available from https://nefroloji.org.tr/tr/formul-ve-hesaplamalar
- Yüksel O, Pehlivan M, Çöven HİK, et al. The changes in the expression levels of β-catenin gene in pre- and post- Kidney Transplants. Transpl Immunol 2021;69:101471.
- Kutukculer N, Clark K, Rigg KM, Forsythe JLR, Proud G, Taylor RMR SBK. The Value of Posttransplant Monitoring of Interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and Soluble CD23 in the Plasma of Renal Allograft Recipients. Transplantation 1995;59(3):333-340.
- Shimizu S, Ueda M, Ozawa S, et al. Detection of IL-2 Receptor Gene Expression in Peripheral Blood from Renal Transplant Patients. Surgery Today 2001;31(12):1058-1064.
- Rysz J, Kocur E, Blaszczak R, Bartnicki P, Stolarek RA, Piechota M. IL-2, IL-6 and IL-8 levels remain unaltered in the course of immunosuppressive therapy after renal transplantation. Cent Eur J Med 2008;3(2):199-202.
- Miller CL, Madsen JC. IL-6 Directed Therapy in Transplantation. Curr Transplant Rep 2021;8(3):191-204.
- Omrani H, Vahid Jasemi S, Sadeghi M, Golmohamadi S, Nephrology SG. Evaluation of Serum Interleukin-6 Levels in the Renal Transplant Recipients: A Systematic Review and Meta-Analysis of Case-Control Studies the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). Journal of Medical Sciences 2019;7(1):174-178.
- Waiser J, Budde K, Katalinic A, Kuerzdörfer M, Rieß R, Neumayer HH. Interleukin-6 expression after renal transplantation. Nephrology Dialysis Transplantation 1997;12(4):753-759.
- Bennett C, Waters A, Moran J, Connell J, Hall W, Hassan J. Predominant Inflammatory and Th1 biased cytokine secretion pre-and post-kidney transplantation. Eastern Journal of Medicine 2011;16:22-25.
- Haouami Y, Dhaouadi T, Sfar I, et al. The role of IL-23/IL-17 axis in human kidney allograft rejection. J Leukoc Biol 2018;104(6):1229-1239.
- Striz I, Eliska K, Eva H, et al. Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft. Immunol Lett 2005;99(1):30-35.
- Wyburn K, Wu H, Yin J, Jose M, Eris J, Chadban S. Macrophage-derived interleukin-18 in experimental renal allograft rejection. Nephrology Dialysis Transplantation 2005;20(4):699-706.
- Zareei N, Miri HR, Karimi MH, et al. Increasing of the interferon-γ gene expression during polyomavirus BK infection in kidney transplant patients. Microb Pathog 2019;129(January):187-194.
- Nazari B, Amirzargar A, Nikbin B, et al. Comparison of the Th1, IFN-γ Secreting Cells and FoxP3 Expression between Patients with Stable Graft Function and Acute Rejection Post Kidney Transplantation. Iran J Allergy Asthma Immunol 2013;12(3):262-268.
- Spivey TL, Uccellini L, Ascierto ML, et al. Gene expression profiling in acute allograft rejection: Challenging the immunologic constant of rejection hypothesis. J Transl Med 2011;9(1):1-22.
- Idriss HT, Naismith JH. TNFα and the TNF receptor superfamily: Structure-function relationship(s). Microsc Res Tech 2000;50(3):184-195.
- Sinuani I, Beberashvili I, Averbukh Z, Sandbank J. Role of IL-10 in the progression of kidney disease. World J Transplant 2013;3(4):91.
- Gao C, Peng F, Xie X, Peng L. The Relationship Between Blood Interleukin-10 and Cardiovascular Mortality and All-Cause Mortality After Kidney Transplantation. Published online 2021.
- Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nature Reviews Nephrology 2016;12(6):325-338.
Hribova P, Kotsch K, Brabcova I, Vitko S, Volk HD, Lacha J. Cytokines and chemokine gene expression in human kidney transplantation. Transplant Proc 2005;37(2):760-763.
- Khanna A, Plummer M, Bromberek C, Bresnahan B, Hariharan S. Expression of TGF-β and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity. Kidney Int 2002;62(6):2257-2263.
- Alvarez CM, Opelz G, Garcia LF, Süsal C. Expression of regulatory tĝ€"cell-related molecule genes and clinical outcome in kidney transplant recipients. Transplantation 2009;87(6):857-863.
- Bunnag S, Allanach K, Jhangri GS, et al. FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable Outcomes. American Journal of Transplantation 2008;8(7):1423-1433.
- Muthukumar T, Dadhania D, Ding R, et al. Messenger RNA for FOXP3 in the Urine of Renal-Allograft Recipients. New England Journal of Medicine 2005;353(22):2342-2351.
- Iwase H, Kobayashi T, Kodera Y, et al. Clinical significance of regulatory T-cell-related gene expression in peripheral blood after renal transplantation. Transplantation 2011;91(2):191-198.
Year 2024,
, 634 - 641, 30.09.2024
Aslı Özkızılcık Koçyiğit
,
Melek Pehlivan
,
Tülay Kılıçaslan Ayna
,
Mustafa Soyöz
,
Erhan Tatar
,
Mehmet Tanrısev
,
İsmail Sert
,
Zeki Soypacacı
,
Cem Tuğmen
,
İbrahim Pirim
Project Number
2019-GAP-TIPF-0006 and 2020-TDR-SABE-011
References
- Turkish Nephrology Coordination [Internet]. Formula and Calculations. [Accessed date: 11 November 2021]. Available from https://nefroloji.org.tr/tr/formul-ve-hesaplamalar
- Yüksel O, Pehlivan M, Çöven HİK, et al. The changes in the expression levels of β-catenin gene in pre- and post- Kidney Transplants. Transpl Immunol 2021;69:101471.
- Kutukculer N, Clark K, Rigg KM, Forsythe JLR, Proud G, Taylor RMR SBK. The Value of Posttransplant Monitoring of Interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and Soluble CD23 in the Plasma of Renal Allograft Recipients. Transplantation 1995;59(3):333-340.
- Shimizu S, Ueda M, Ozawa S, et al. Detection of IL-2 Receptor Gene Expression in Peripheral Blood from Renal Transplant Patients. Surgery Today 2001;31(12):1058-1064.
- Rysz J, Kocur E, Blaszczak R, Bartnicki P, Stolarek RA, Piechota M. IL-2, IL-6 and IL-8 levels remain unaltered in the course of immunosuppressive therapy after renal transplantation. Cent Eur J Med 2008;3(2):199-202.
- Miller CL, Madsen JC. IL-6 Directed Therapy in Transplantation. Curr Transplant Rep 2021;8(3):191-204.
- Omrani H, Vahid Jasemi S, Sadeghi M, Golmohamadi S, Nephrology SG. Evaluation of Serum Interleukin-6 Levels in the Renal Transplant Recipients: A Systematic Review and Meta-Analysis of Case-Control Studies the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). Journal of Medical Sciences 2019;7(1):174-178.
- Waiser J, Budde K, Katalinic A, Kuerzdörfer M, Rieß R, Neumayer HH. Interleukin-6 expression after renal transplantation. Nephrology Dialysis Transplantation 1997;12(4):753-759.
- Bennett C, Waters A, Moran J, Connell J, Hall W, Hassan J. Predominant Inflammatory and Th1 biased cytokine secretion pre-and post-kidney transplantation. Eastern Journal of Medicine 2011;16:22-25.
- Haouami Y, Dhaouadi T, Sfar I, et al. The role of IL-23/IL-17 axis in human kidney allograft rejection. J Leukoc Biol 2018;104(6):1229-1239.
- Striz I, Eliska K, Eva H, et al. Interleukin 18 (IL-18) upregulation in acute rejection of kidney allograft. Immunol Lett 2005;99(1):30-35.
- Wyburn K, Wu H, Yin J, Jose M, Eris J, Chadban S. Macrophage-derived interleukin-18 in experimental renal allograft rejection. Nephrology Dialysis Transplantation 2005;20(4):699-706.
- Zareei N, Miri HR, Karimi MH, et al. Increasing of the interferon-γ gene expression during polyomavirus BK infection in kidney transplant patients. Microb Pathog 2019;129(January):187-194.
- Nazari B, Amirzargar A, Nikbin B, et al. Comparison of the Th1, IFN-γ Secreting Cells and FoxP3 Expression between Patients with Stable Graft Function and Acute Rejection Post Kidney Transplantation. Iran J Allergy Asthma Immunol 2013;12(3):262-268.
- Spivey TL, Uccellini L, Ascierto ML, et al. Gene expression profiling in acute allograft rejection: Challenging the immunologic constant of rejection hypothesis. J Transl Med 2011;9(1):1-22.
- Idriss HT, Naismith JH. TNFα and the TNF receptor superfamily: Structure-function relationship(s). Microsc Res Tech 2000;50(3):184-195.
- Sinuani I, Beberashvili I, Averbukh Z, Sandbank J. Role of IL-10 in the progression of kidney disease. World J Transplant 2013;3(4):91.
- Gao C, Peng F, Xie X, Peng L. The Relationship Between Blood Interleukin-10 and Cardiovascular Mortality and All-Cause Mortality After Kidney Transplantation. Published online 2021.
- Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nature Reviews Nephrology 2016;12(6):325-338.
Hribova P, Kotsch K, Brabcova I, Vitko S, Volk HD, Lacha J. Cytokines and chemokine gene expression in human kidney transplantation. Transplant Proc 2005;37(2):760-763.
- Khanna A, Plummer M, Bromberek C, Bresnahan B, Hariharan S. Expression of TGF-β and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity. Kidney Int 2002;62(6):2257-2263.
- Alvarez CM, Opelz G, Garcia LF, Süsal C. Expression of regulatory tĝ€"cell-related molecule genes and clinical outcome in kidney transplant recipients. Transplantation 2009;87(6):857-863.
- Bunnag S, Allanach K, Jhangri GS, et al. FOXP3 Expression in Human Kidney Transplant Biopsies Is Associated with Rejection and Time Post Transplant but Not with Favorable Outcomes. American Journal of Transplantation 2008;8(7):1423-1433.
- Muthukumar T, Dadhania D, Ding R, et al. Messenger RNA for FOXP3 in the Urine of Renal-Allograft Recipients. New England Journal of Medicine 2005;353(22):2342-2351.
- Iwase H, Kobayashi T, Kodera Y, et al. Clinical significance of regulatory T-cell-related gene expression in peripheral blood after renal transplantation. Transplantation 2011;91(2):191-198.