Characterization of Minor HA-1 in Patients Who Underwent Living Donor Kidney Transplantation

Yıl 2010, , 265 - 269, 01.04.2010

Çiğdem Kekik Fatma Savran Oğuz Yalçın Seyhun Yaşar Çalışkan Aydın Türkmen Mahmut Çarin

https://doi.org/10.5174/tutfd.2009.02429.0

Öz

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Anahtar Kelimeler

Transplantation; minor histocompatibility antigens; rejection

Canlı Donörden Böbrek Transplantasyonu Yapılan Hastalarda Minör HA-1 Dağılımı

Öz

Amaç: Son dönem böbrek yetersizliği (SDBY) olan hastalar için hayat standartlarını arttıran bir tedavi yöntemi olan böbrek naklinde HLA uyumunun önemi bilinen bir gerçektir. Alıcı ve verici arasındaki İnsan Lökosit Antijenleri (Human Leukocyte Antigens, HLA) uyumunun, allojenik böbrek transplantasyonu sonrası graft sağkalımı üzerine önemli bir etkisi vardır. Ancak HLA identik kardeşler arası yapılan transplantlar da graft kaybı ile sonlanabilmektedir. Minör histokompatibilite antijenleri (mHag) HA-1, 19. kromozom üzerindeki diallelik genlerce kodlanan, 9 aminoasitlik düşük polimorfizm gösteren immünojenik bir peptiddir. Minör histokompatibilite antijenleri, HLA uyumlu solid organ transplantasyonlarının graft rejeksiyonu için potansiyel bir risk faktörüdür. Yaptığımız bu çalışmada böbrek transplantasyonunda mHA-1 uyumu veya uyumsuzluğunun, transplant sonrası graft sağkalımı ile ilişkisini araştırmayı amaçladık.Hastalar ve Yöntemler: Son dönem böbrek yetersizliği tanısı konmuş 59 hasta ile onların akraba vericileri çalışmaya alındı. Minör HA-1 genotipleri ise PCR-SSP yöntemiyle ticari kitler kullanılarak yapıldı.Bulgular: 59 hastada HH, RR, HR genotiplerinin sıklıkları sırası ile %17, %25 ve %58 idi. Rejeksiyon/rejeksiyon atağı saptanması ile mHA-1 uyumu açısından anlamlı bir fark saptanmadı (p=0.73, Or=1.44, güven aralığı=0.36-5.74; Fischer’s Exact Test). Kronik Allograft Nefropatisi (KAN) gelişimi ile mHA-1 uyumu açısından anlamlı bir fark saptanmadı (p=0.61, Or=2.89, güven aralığı=0.28-29.57; Fischer’s Exact Test).Sonuç: Yaptığımız çalışmada canlı donörden böbrek nakillerinde rejeksiyon ile HA-1 uyumsuzluğu arasında anlamlı bir fark saptayamadık

Anahtar Kelimeler

Transplantasyon, minör histokompatibilite antijenleri, rejeksiyon

Kaynakça

• Opelz G; Collaborative Transplant Study. Non-HLA trans- plantation immunity revealed by lymphocytotoxic antibod- ies. Lancet 2005;365:1570-6.
• Terasaki PI. Deduction of the fraction of immunologic and non-immunologic failure in cadaver donor transplants. In: Cecka JM, Terasaki PI, editors. Clinal transplants. Los Angeles, CA: UCLA Immunogenetics Center; 2002. p. 449-52.
• Snell GD. Methods for the study of histocompatibility genes. J Genet 1948;49:87-108.
• Tseng LH, Lin MT, Hansen JA, Gooley T, Pei J, Smith AG, et al. Correlation between disparity for the minor histo- compatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow trans- plantation. Blood 1999;94:2911-4.
• den Haan JM, Meadows LM, Wang W, Pool J, Blokland E, Bishop TL, et al. The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymor- phism. Science 1998;279:1054-7.
• Goulmy E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immu- notherapy. Immunol Rev 1997;157:125-40.
• Wallny HJ, Rammensee HG. Identification of classical minor histocompatibility antigen as cell-derived peptide. Nature 1990;343:275-8.
• Loveland B, Wang CR, Yonekawa H, Hermel E, Lindahl KF. Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Cell 1990;60:971-80.
• Rötzschke O, Falk K, Wallny HJ, Faath S, Rammensee HG. Characterization of naturally occurring minor his- tocompatibility peptides including H-4 and H-Y. Science 1990;249:283-7.
• Falk K, Rötzschke O, Rammensee HG. Cellular peptide composition governed by major histocompatibility com- plex class I molecules. Nature 1990;348:248-51.
• Goulmy E. Minor histocompatibility antigens: from trans- plantation problems to therapy of cancer. Hum Immunol 2006;67:433-8.
• Goulmy E, Gratama JW, Blokland E, Zwaan FE, van Rood JJ. A minor transplantation antigen detected by MHC- restricted cytotoxic T lymphocytes during graft-versus-host disease. Nature 1983;302:159-61.
• Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E. Feasibility of immunotherapy of relapsed leu- kemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histo- compatibility antigens. Blood 1999;93:2336-41.
• Graff RJ, Hildemann WH, Snell GD. Histocompatibility genes of mice. VI. Allografts in mice congenic at various non-H-2 histocompatibility loci. Transplantation 1966;4:425-37.
• Goulmy E, Termijtelen A, Bradley BA, van Rood JJ. Alloimmunity to human H-Y. Lancet 1976;2:1206.
• Goulmy E, Termijtelen A, Bradley BA, van Rood JJ. Y-antigen killing by T cells of women is restricted by HLA. Nature 1977;266:544-5.
• Mutis T, Gillespie G, Schrama E, Falkenburg JH, Moss P, Goulmy E. Tetrameric HLA class I-minor histocom- patibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lympho- cytes in patients with graft-versus-host disease. Nat Med 1999;5:839-42.
• Dickinson AM, Wang XN, Sviland L, Vyth-Dreese FA, Jackson GH, Schumacher TN, et al. In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nat Med 2002;8:410-4.
• Krishnan NS, Higgins RM, Lam FT, Kashi H, Jobson S, Ramaiyan K, et al. HA-1 mismatch has significant effect in chronic allograft nephropathy in clinical renal transplanta- tion. Transplant Proc 2007;39:1439-45.
• Yang J, Jaramillo A, Liu W, Olack B, Yoshimura Y, Joyce S, et al. Chronic rejection of murine cardiac allografts discordant at the H13 minor histocompatibility antigen correlates with the generation of the H13-specific CD8+ cytotoxic T cells. Transplantation 2003;76:84-91.
• Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 1991;11:298-300.
• Middleton D, Nelson SD, Martin J. Sources of HLA typing sera. Ulster Med J 1978;47:162-4.
• Olerup O, Zetterguist H. DR "low-resolution" PCR-SSP typing--a correction and an up-date. Tissue Antigens 1993;41:55-6.
• Jordan F, McWhinnie AJ, Turner S, Gavira N, Calvert AA, Cleaver SA, et al. Comparison of HLA-DRB1 typing by DNA-RFLP, PCR-SSO and PCR-SSP methods and their application in providing matched unrelated donors for bone marrow transplantation. Tissue Antigens 1995;45:103-10.
• Rodríguez PC, Arroyave IH, Mejía G, García LF. Detection of alloantibodies against non-HLA antigens in kidney trans- plantation by flow cytometry. Clin Transplant 2000;14:472-8.
• Goulmy E, Schipper R, Pool J, Blokland E, Falkenburg JH, Vossen J, et al. Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation. N Engl J Med 1996;334:281-5.
• Nishida T, Akatsuka Y, Morishima Y, Hamajima N, Tsujimura K, Kuzushima K, et al. Clinical relevance of a newly identified HLA-A24-restricted minor histocompat- ibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant. Br J Haematol 2004;124:629-35.
• Akatsuka Y, Warren EH, Gooley TA, Brickner AG, Lin MT, Hansen JA, et al. Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling. Br J Haematol 2003;123:671-5.
• Pérez-García A, De la Cámara R, Torres A, González M, Jiménez A, Gallardo D. Minor histocompatibility anti- gen HA-8 mismatch and clinical outcome after HLA- identical sibling donor allogeneic stem cell transplantation. Haematologica 2005;90:1723-4.
• Gallardo D, Aróstegui JI, Balas A, Torres A, Caballero D, Carreras E, et al. Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donor transplantation. Br J Haematol 2001;114:931-6.
• Simpson E, Scott D, James E, Lombardi G, Cwynarski K, Dazzi F, et al. Minor H antigens: genes and peptides. Eur J Immunogenet 2001;28:505-13.
• Cai J, Lee J, Jankowska-Gan E, Derks R, Pool J, Mutis T, et al. Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance. J Exp Med 2004;199:1017-23.
• Heinold A, Opelz G, Scherer S, Ruhenstroth A, Laux G, Doehler B, et al. Role of minor histocompatibility antigens in renal transplantation. Am J Transplant 2008;8:95-102.