Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 5, May, p. 629–633

doi: 10.17219/acem/121510

Publication type: review

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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The significance of angiotensin II type 1 receptor (AT1 receptor) in renal transplant injury

Agnieszka Sas-Strózik1,A,B,C,D,E,F, Magdalena Krajewska1,E,F, Mirosław Banasik1,A,B,C,D,E,F

1 Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland

Abstract

Humoral response beyond human leukocyte antigen (HLA) is of great interest in the transplant community. We decided to summarize the data on a new antigenic target called angiotensin II type 1 receptor (AT1 receptor). Non-HLA antibodies can now be detected in routine clinical care of patients after transplantation, but their role is not fully understood. Numerous analyses showed that non-HLA response may exert a higher risk of allograft rejection and allograft loss independently of the HLA system. Non-HLA response may even have a higher rate of antibody-mediated rejection. Information regarding antigen target, as well as the pathophysiology of its antibodies and diagnostic tools, is essential for a better understanding of non-HLA humoral response. Angiotensin II type 1 receptors are the most recognized target for non-HLA antibodies. Anti-AT1R Abs (anti-angiotensin II type 1-receptor-activating antibodies) may identify renal transplant patients at higher risk of graft rejection and loss. The presence of AT1 receptor expression analyzed together with anti-AT1R Abs should be considered for better transplant immunological risk assessment. Further assessment is required for a better understanding and to create appropriate therapeutic strategies.

Key words

angiotensin AT1 receptor, non-HLA antibodies, anti-AT1R Abs, antibody-mediated rejection, renal transplantation

References (35)

  1. Sellares J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: The dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388–399.
  2. Terasaki PI. Humoral theory of transplantation. Am J Transplant. 2003;3(6):665–673.
  3. Cai J, Terasaki PI. Humoral theory of transplantation: Mechanism, prevention, and treatment. Hum Immunol. 2005;66(4):334–342.
  4. Terasaki PI, Cai J. Humoral theory of transplantation: Further evidence. Curr Opin Immunol. 2005;17(5):541–545.
  5. Dragun D, Philippe A, Catar R. Role of non-HLA antibodies in organ transplantation. Curr Opin Organ Transplant. 2012;17(4):440–445.
  6. Taniguchi M, Rebellato LM, Cai J, et al. Higher risk of kidney graft failure in the presence of anti-angiotensin II type-1 receptor antibodies. Am J Transplant. 2013;13(10):2577–2589.
  7. Giral M, Foucher Y, Dufay A, et al. Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant. 2013;13(10):2567–2576.
  8. Banasik M, Boratynska M, Koscielska-Kasprzak K, et al. The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes. Transpl Int. 2014;27(10):1029–1038.
  9. Gasc JM, Shanmugam S, Sibony M, Corvol P. Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension. 1994;24(5):531–537.
  10. Gurley SB, Riquier-Brison ADM, Schnermann J, et al. AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metab. 2011;13(4):469–475.
  11. Reinsmoen NL, Lai CH, Heidecke H, et al. Anti-angiotensin type 1 receptor antibodies associated with antibody-mediated rejection in donor HLA antibody negative patients. Transplantation. 2010;90(12):1473–1477.
  12. Hunyady L, Catt KJ. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 2006;20(5):953–970.
  13. Dragun D. Humoral responses directed against non-human leukocyte antigens in solid-organ transplantation. Transplantation. 2008;86(8):1019–1025.
  14. Miller JA, Scholey JW. The impact of renin-angiotensin system polymorphisms on physiological and pathophysiological processes in humans. Curr Opin Nephrol. 2004;13(1):101–106.
  15. Dragun D, Muller DN, Brasen JH, et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. NEJM. 2005;352(6):558–569.
  16. Dzau VJ. Theodore Cooper Lecture: Tissue angiotensin and pathobiology of vascular disease: A unifying hypothesis. Hypertension. 2001;37(4):1047–1052.
  17. Banasik M, Boratynska M, Koscielska-Kasprzak K, et al. Non-HLA antibodies: Angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss. Transplant Proc. 2014;46(8):2618–2621.
  18. Banasik M, Boratynska M, Koscielska-Kasprzak K, et al. The impact of de novo donor-specific anti-human leukocyte antigen antibodies on 5-year renal transplant outcome. Transplant Proc. 2013;45(4):1449–1452.
  19. Sas A, Donizy P, Koscielska-Kasprzak K, et al. Histopathological relevance of angiotensin II type 1 receptor in renal transplant biopsy. Transplant Proc. 2018;50(6):1847–1849.
  20. Sas-Strózik A, Donizy P, Koscielska-Kasprzak K, et al. Angiotensin II type 1 receptor (AT1R) expression in renal transplant biopsies and anti-AT1R antibodies in serum indicates the risk of transplant loss. Transplant Proc. https://doi.org/10.1016/j.transproceed.2020.01.126
  21. Michielsen LA, van Zuilen AD, Krebber MM, Verhaar MC, Otten HG. Clinical value of non-HLA antibodies in kidney transplantation: Still an enigma? Transplantation Rev. 2016;30(4):195–202.
  22. Wang S, Zhang C, Wang J, et al. Endothelial cells in antibody-mediated rejection of kidney transplantation: Pathogenesis mechanisms and therapeutic implications. J Immunol Res. 2017;2017:8746303.
  23. Reinsmoen NL. Role of angiotensin II type 1 receptor-activating antibodies in solid organ transplantation. Hum Immunol. 2013;74(11):1474–1477.
  24. Kranzhofer R, Schmidt J, Pfeiffer CA, Hagl S, Libby P, Kubler W. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1999;19(7):1623–1629.
  25. Rouet-Benzineb P, Gontero B, Dreyfus P, Lafuma C. Angiotensin II induces nuclear factor – kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway. J Mol Cell Cardiol. 2000;32(10):1767–1778.
  26. Oliveira L, Costa-Neto CM, Nakaie CR, Schreier S, Shimuta SI, Paiva AC. The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure. Physiol Rev. 2007;87(2):565–592.
  27. Zhang H, Unal H, Gati C, et al. Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell. 2015;161(4):833–844.
  28. Xia Y, Kellems RE. Angiotensin receptor agonistic autoantibodies and hypertension: Preeclampsia and beyond. Circ Res. 2013;113(1):78–87.
  29. Crowley SD, Gurley SB, Herrera MJ, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. PNAS. 2006;103(47):17985–17990.
  30. Banasik M, Boratynska M, Koscielska-Kasprzak K, et al. Long-term follow-up of non-HLA and anti-HLA antibodies: Incidence and importance in renal transplantation. Transplant Proc. 2013;45(4):1462–1465.
  31. Fuss A, Hope CM, Deayton S, et al. C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies. Nephrology (Carlton). 2015;20(7):467–473.
  32. Lefaucheur C, Viglietti D, Bouatou Y, et al. Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Kidney Int. 2019;96(1):189–201.
  33. Velidedeoglu E, Cavaillé-Coll MW, Bala S, Belen OA, Wang Y, Albrecht R. Summary of 2017 FDA Public Workshop: Antibody-mediated rejection in kidney transplantation. Transplantation. 2018;102(6):e257–e264. doi:10.1097/TP.0000000000002141
  34. Carroll RP, Riceman M, Hope CM, et al. Angiotensin II type-1 receptor antibody (AT1Rab) associated humoral rejection and the effect of peri operative plasma exchange and candesartan. Hum Immunol. 2016;77(12):1154–1158.
  35. Weidanz JA, Jacobson LM, Muehrer RJ, et al. ATR blockade reduces IFN-gamma production in lymphocytes in vivo and in vitro. Kidney Int. 2005;67(6):2134–2142.
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