İmmünsüpresif ilaçlar olmadan organ nakli mümkün mü?

Yıl 2018, Cilt: 3 Sayı: 1-2, 17 - 20, 04.04.2019

Mine Ün Oytun Erbaş

Öz

Organ ve hücre nakilleri geniş çapta kabul gören tedaviler haline gelmiştir. Ancak nakillerden sonra ömür boyu kullanılması zorunlu olan immünsüpresif ilaçlar yüksek düzeyde toksiktir. İlaçları kullanmadan nakil yapılabilmesi için geliştirilen yöntemler alıcıda donöre özgü toleransı tetiklemeye çalışır. Hematopoietik kök hücre nakli sonucu oluşan kimerizmin, insanlar dahil birçok türde donöre özgü toleransı indüklediği gösterilmiştir.

Anahtar Kelimeler

Hematopoietik kök hücre nakli, immünsüpresif ilaçlar, organ nakli

Kaynakça

• 1. Lim J, Bae SC, Kim K. Understanding HLA associations from SNP summary association statistics. Sci Rep 2019;9:1337. 2. Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med 2012;4:124ra28. 3. Barry JM. Immunosuppressive drugs in renal transplantation. A review of the regimens. Drugs 1992;44:554-66. 4. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994;331:365-76. 5. Helderman JH, Van Buren DH, Amend WJ Jr, Pirsch JD. Chronic immunosuppression of the renal transplant patient. J Am Soc Nephrol 1994;4(8 Suppl):S2-9. 6. Leventhal JR, Ildstad ST. Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell Infusion: The importance of durable chimerism. Hum Immunol 2018;79:272-6. 7. Ildstad ST, Shirwan H, Leventhal J. Is durable macrochimerism key to achieving clinical transplantation tolerance? Curr Opin Organ Transplant 2011;16:343-4. 8. Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature 1984;307:168-70. 9. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349:931-40. 10. Sénéchal M, Dorent R, du Montcel ST, Ghossou JJ, Pavie A, Petitclerc T, et al. End-stage renal failure and cardiac mortality after heart transplantation. Clin Transplant 2004;18:1-6. 11. Li C, Yang CW. The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol 2009;5:513-9. 12. Orloff MS, DeMara EM, Coppage ML, Leong N, Zuo XJ, Prehn J, et al. Alterations of the interleukin-4 pathway in production of tolerance by mixed hematopoietic chimerism. Surgery 1995;118:212-9. 13. Kawai T, Cosimi AB, Sachs DH. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant 2011;16:366-71. 14. Huang CA, Fuchimoto Y, Scheier-Dolberg R, Murphy MC, Neville DM Jr, Sachs DH. Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. J Clin Invest 2000;105:173-81. 15. Khaddour K, Mewawalla P. Hematopoietic Stem Cell Transplantation. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018-. 2019 Jan 22. 16. Sargın D. Graft fonksiyonu ve kimerizm. 7. Ulusal Kemik ‹li¤i Transplantasyonu ve Kök Hücre Tedavileri Kongresi. 08-10 Mart 2012, Antalya, Türkiye. Available from: http://www.thd.org.tr/thdData/Books/232/graft-fonksiyonu-ve-kimerizm-deniz-sargin.pdf 17. Hamerton JL, Harnes DWH. Cytological identification of radiation chimeras. Nature 1956;177:239-47. 18. Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 2008;358:362-8. 19. Sachs DH, Sykes M, Kawai T, Cosimi AB. Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol 2011;23:165-73. 20. Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008;358:353-61. 21. Kaufman C, Colson YL, Wren SM, Watkins S, Simmons RL, Ildstad ST. Phenotypic characterization of a novel bone marrow-derived cell that facilitates engraftment of allogeneic bone marrow stem cells. Blood 1994;84:2436-46. 22. Fugier-Vivier IJ, Rezzoug F, Huang Y, Graul-Layman AJ, Schanie CL, Xu H, et al. Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment. J Exp Med 2005;201:373-83. 23. Colson YL, Christopher K, Glickman J, Taylor KN, Wright R, Perkins DL. Absence of clinical GVHD and the in vivo induction of regulatory T cells after transplantation of facilitating cells. Blood 2004;104:3829-35. 24. Akpek G. Kronik Graft -versus- Host Hastalı¤ı: Yeni Tanımlama ve Sınıflama Kriterleri. 9. Mezuniyet Sonrası E¤itim Kursu. Available from: http://www.thd.org.tr/thdData/userfiles/file/9_MSEK_11.pdf