MİNÖR DOKU UYGUNLUK ANTİJENLERİNİN KARAKTERİZASYONU VE ALLOGENEİK HEMATOPOETİK KÖK HÜCRE NAKLİNDEKİ ROLÜ: TÜRKİYE’DE TEK MERKEZ DENEYİMİ
Abstract
Amaç: Minör doku uygunluk antijenleri (mHAg), polimorfik esansiyel peptitlerden
oluşan epitoplar olup sınıf I ve II HLA allele çeşitleri ile sınırlı olan
bir T hücresi yanıtı ortaya çıkarırlar. Son yıllarda, farklı popülasyonlarda
polimorfik bölgelerin dağılımı hakkında kapsamlı araştırmalar yapılmıştır.
Alıcı ve verici arasındaki mHAg uyumsuzluğu, HLA tam uyumlu transplantasyona
rağmen güçlü bir hücresel immün yanıtı başlatabilir. Çalışmamızda
çeşitli hematolojik hastalıklar nedeniyle hematopoietik kök hücre transplantasyonu
(AKHN) yapılan hastalarda mHAg sıklığının belirlenmesi
amaçlanmıştır.
Gereç ve Yöntem: Çalışma popülasyonu 200 sağlıklı bireyi, allojenik AKHN
adayları olarak HLA’sı tiplendirilmiş olan 150 hastayı ve 20 allojenik AKHN
alıcısı/donörünü içermektedir. mHAg’lar, polimeraz zincir reaksiyonu (PZR)
ve diziye özgü primer (SSP) yöntemleri kullanılarak belirlendi.
Bulgular: Hastaların alel frekansları ve genotipleri sağlıklı grup ile karşılaştırıldığında,
immünojenik veya immünojenik olmayan alel frekansları açısından
fark anlamlı değildi. Sağlıklı grupta immünojenik homozigot H aleli (HH
genotipi) olan bireyler daha azdı ve bu fark istatistiksel olarak anlamlıydı.
Çalışma popülasyonumuz küçük olmasına rağmen, 20 transplant hastasından
ve donöründen alınan verilere göre, 10 hastanın %50’sinin minör uyumsuzluk
kaynaklı Graft versus host hastalığı (GVHH) olduğu gözlendi.
Sonuç: Sağlıklı Türk popülasyonunda ve malign hematolojik hastalığı olan
hastalarda mHAg frekanslarının belirlenmesinin immün yanıtın anlaşılmasına
katkı sağlayacağını düşünmekteyiz.
Keywords
Minör Histo Uygunluk Antijenleri Allojenik Hematopoietik Kök Hücre Nakli Graft-versus-host hastalığı
Supporting Institution
İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi
Project Number
292/05012005
References
- 1. 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 polymorphism. Science 1998;279(5353):1054-7. google scholar
- 2. Schreuder GM, Pool J, Blokland E, van Els C, Bakker A, van Rood JJ, et al: A genetic analysis of human minor histocompatibility antigens demonstrates Mendelian segregation independent of HLA. Immunogenetics 1993;38(2):98-105. google scholar
- 3. Chao NJ. Minors come of age: minor histocompatibility antigens and graft-versus-host disease. Biol Blood Marrow Transplant 2004;10(4):215-23. google scholar
- 4. Falkenburg JHF, van de Corput L, Marijt EWA, Willemze R. Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol 2003;31(9):743-51. google scholar
- 5. Spierings E, Wieles B, Goulmy E. Minor histocompatibility antigens— big in tumour therapy. Trends Immunol 2004;25(2):56-60. google scholar
- 6. Bleakley M, Riddell SR. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer 2004;4(5):371-80. google scholar
- 7. Spierings E, Hendriks M, Absi L, Canossi A, Chhaya S, Crowley J, et al. Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations. PLoS Genet 2007;3(6):103. google scholar
- 8. Terlizzi SD, Zino E, Mazzi B, Magnani C, Tresoldi C, Perna SK, et al. Therapeutic and Diagnostic Applications of Minor Histocompatibility Antigen HA-1 and HA-2 Disparities in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey of Different Populations. Biol Blood Marrow Transplant 2006:12(1):95-101. google scholar
- 9. Romaniuk DS, Postovskaya AM, Khmelevskaya AA, Malko DB and Efimov GA. Rapid Multiplex Genotyping of 20 HLA-A*02:01 Restricted Minor Histocompatibility Antigens. Front Immunol 2019;10:1226. doi: 10.3389/fimmu.2019.01226. google scholar
- 10. Tseng LH, Lin MT, Martin PJ, Pei J, Smith AG, Hansen JA. Definition of the gene encoding the minor histocompatibility antigen HA-1 and typing for HA-1 from genomic DNA. Tissue Antigen 1998;52(4):305-11. google scholar
- 11. den Haan JM, Sherman NE, Blokland E, Huczko E, Koning F, Drijfhout JW, et al. Identification of a graft versus host disease-associated human minor histocompatibility antigen. Science 1995:9;268(5216):1476-80. google scholar
- 12. Goulmy E, Schipper R, Pool J, Blokland E, Falkenburg JH, Vossen J, et al. Mismatches of minor histocompatibity antigens between HLA identical donors and recipients and the development of graft -versus host disease after bone marrow transplantation. New Engl J Med 1996:334(5):281-5. google scholar
- 13. Tanaka J. Target antigens for graft-versus-host disease (GVHD) and graft-versus-leukemia/tumor (GVL/T). Nihon Rinsho 2003;61(9):1512-9. google scholar
- 14. Kotzampasaki EM, Spyropoulou-Vlachou MS, Kalofoutis C, Vrani V, Kalofoutis A, Stavropoulos-Giokas C, et al: Minor histocompatibility antigen HA-1 anf HPA-5 polymorphisms in HLA identical related bone marrow transplantation. Transplant Proc 2004;36(6):1735-8. google scholar
- 15. Falkenburg JH, Smit WM, Willemze R. Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia. Immunol Rev 1997;157:223-30. google scholar
- 16. Goulmy E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev 1997;157:125-40. google scholar
- 17. Lansford JL, Dharmasiri U, Chai S, Hunsucker SA, Bortone DS, Keating JE, et al. Computational modeling and confirmation of leukemia-associated minör histocompatibility antigens. Blood Adv 2018;28;2(16):2052-62. google scholar
- 18. Falkenburg JH, Marijt WAF, Heemskerk MHM, Willemze R. Minor histocompatibility antigens as targets of graft-versus-leukemia reactions. Curr Opin Hematol 2002;9(6):497-502. google scholar
- 19. Ferrera JL. Paradigm shift for graft versus host disease. Bone Marrow Transplant 1994;14(2):183-4. google scholar
- 20. Ferrera JL, Antin JH. The pathophysiology of graft versus host disease. In: Thomas ED, Blume KG, Forman SJ, editors. Hematopoietic cell transplantation. USA: Blackwell Science; 1999.p.305-15. google scholar
- 21. Hagglund H, Boström L, Remberger M, Ljungman P, Nilsson B, Ringden O. Risk factors for acute graft versus host disease in 219 consecutive HLA identical bone marrow transplant recipients. Bone Marrow Transplant 1995;16(6):747-53. google scholar
- 22. Tseng LH, Lin MT, Hansen JA, Gooley T, Pei J, Smith AG et al. Correlation between Disparity for the Minor Histocompatibility Antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation. Blood 1999; 94(8):2911-4. google scholar
- 23. Wang W, Huang H, Halagan M, Vierra-Green C, Heuer M, Brelsford JE, et al. Chromosome Y-encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant. Blood Adv 2018;9;2(19):2419-29. google scholar
- 24. Goulmy E. Minor histocompatibility antigens: allo target molecules for tumor-specific immunotherapy. Cancer J 2004;10(1):1-7. google scholar
- 25. Hambach L, Goulmy E. Immunotherapy of cancer through targeting of minor histocompatibility antigens. Curr Opin Immunol 2005;17(2):202-10. google scholar
- 26. Gustincich S, Manfiolett G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Bio Techniques 1991;11(3):298-302. google scholar
CHARACTERIZATION OF MINOR HISTOCOMPATIBILITY ANTIGENS AND THEIR ROLE IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: SINGLE CENTER EXPERIENCE IN TURKEY
Abstract
Objective: The minor histocompatibility antigens (mHAgs) are the
epitopes composed of polymorphic essential peptides, and they create T
cell response limited to a variety of class I and II HLA alleles. In recent
years, there has been extensive research on the distribution of
polymorphic regions in different populations. The incompatibility between
recipient and donor, may initiate a strong cellular immune response
despite HLA full-matched transplantation. We determined the frequency
of minor antigens among hematopoietic stem cell transplantation (HSCT)
recipients who underwent transplantation for various hematological
diseases.
Material and Methods: The study population included 200 healthy
individuals, 150 HLA-typed patients who were candidates for allogeneic
HSCT, and 20 recipients/donors with allogeneic transplants. Minor HAgs
identified by using polymerase chain reaction (PCR) and sequence specific
primer (SSP) methods.
Results: When the allele frequencies and genotypes of the patients were
compared with those of the healthy group, the difference was not
significant regarding to immunogenic or non-immunogenic allele
frequencies. The individuals with immunogenic homozygous H allele (HH
genotype) were a few more in the healthy group, and this difference
proved to be statistically significant. In fact, our study population
Insufficient though the number was, based on the data received from 20
transplant patients and donors, GvHD was observed in 5 of 10 patients
who had minor incompatibility.
Conclusion: We assume that determining the mHAg frequencies in the
healthy Turkish population and in patients with malignant hematological
diseases will likely contribute to the understanding of the immune
response.
Keywords
Minor Histocompatibility Antigens Allogeneic Hematopoietic Stem Cell Transplantation Graft-versus-host disease.
Project Number
292/05012005
References
- 1. 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 polymorphism. Science 1998;279(5353):1054-7. google scholar
- 2. Schreuder GM, Pool J, Blokland E, van Els C, Bakker A, van Rood JJ, et al: A genetic analysis of human minor histocompatibility antigens demonstrates Mendelian segregation independent of HLA. Immunogenetics 1993;38(2):98-105. google scholar
- 3. Chao NJ. Minors come of age: minor histocompatibility antigens and graft-versus-host disease. Biol Blood Marrow Transplant 2004;10(4):215-23. google scholar
- 4. Falkenburg JHF, van de Corput L, Marijt EWA, Willemze R. Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol 2003;31(9):743-51. google scholar
- 5. Spierings E, Wieles B, Goulmy E. Minor histocompatibility antigens— big in tumour therapy. Trends Immunol 2004;25(2):56-60. google scholar
- 6. Bleakley M, Riddell SR. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer 2004;4(5):371-80. google scholar
- 7. Spierings E, Hendriks M, Absi L, Canossi A, Chhaya S, Crowley J, et al. Phenotype Frequencies of Autosomal Minor Histocompatibility Antigens Display Significant Differences among Populations. PLoS Genet 2007;3(6):103. google scholar
- 8. Terlizzi SD, Zino E, Mazzi B, Magnani C, Tresoldi C, Perna SK, et al. Therapeutic and Diagnostic Applications of Minor Histocompatibility Antigen HA-1 and HA-2 Disparities in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey of Different Populations. Biol Blood Marrow Transplant 2006:12(1):95-101. google scholar
- 9. Romaniuk DS, Postovskaya AM, Khmelevskaya AA, Malko DB and Efimov GA. Rapid Multiplex Genotyping of 20 HLA-A*02:01 Restricted Minor Histocompatibility Antigens. Front Immunol 2019;10:1226. doi: 10.3389/fimmu.2019.01226. google scholar
- 10. Tseng LH, Lin MT, Martin PJ, Pei J, Smith AG, Hansen JA. Definition of the gene encoding the minor histocompatibility antigen HA-1 and typing for HA-1 from genomic DNA. Tissue Antigen 1998;52(4):305-11. google scholar
- 11. den Haan JM, Sherman NE, Blokland E, Huczko E, Koning F, Drijfhout JW, et al. Identification of a graft versus host disease-associated human minor histocompatibility antigen. Science 1995:9;268(5216):1476-80. google scholar
- 12. Goulmy E, Schipper R, Pool J, Blokland E, Falkenburg JH, Vossen J, et al. Mismatches of minor histocompatibity antigens between HLA identical donors and recipients and the development of graft -versus host disease after bone marrow transplantation. New Engl J Med 1996:334(5):281-5. google scholar
- 13. Tanaka J. Target antigens for graft-versus-host disease (GVHD) and graft-versus-leukemia/tumor (GVL/T). Nihon Rinsho 2003;61(9):1512-9. google scholar
- 14. Kotzampasaki EM, Spyropoulou-Vlachou MS, Kalofoutis C, Vrani V, Kalofoutis A, Stavropoulos-Giokas C, et al: Minor histocompatibility antigen HA-1 anf HPA-5 polymorphisms in HLA identical related bone marrow transplantation. Transplant Proc 2004;36(6):1735-8. google scholar
- 15. Falkenburg JH, Smit WM, Willemze R. Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia. Immunol Rev 1997;157:223-30. google scholar
- 16. Goulmy E. Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. Immunol Rev 1997;157:125-40. google scholar
- 17. Lansford JL, Dharmasiri U, Chai S, Hunsucker SA, Bortone DS, Keating JE, et al. Computational modeling and confirmation of leukemia-associated minör histocompatibility antigens. Blood Adv 2018;28;2(16):2052-62. google scholar
- 18. Falkenburg JH, Marijt WAF, Heemskerk MHM, Willemze R. Minor histocompatibility antigens as targets of graft-versus-leukemia reactions. Curr Opin Hematol 2002;9(6):497-502. google scholar
- 19. Ferrera JL. Paradigm shift for graft versus host disease. Bone Marrow Transplant 1994;14(2):183-4. google scholar
- 20. Ferrera JL, Antin JH. The pathophysiology of graft versus host disease. In: Thomas ED, Blume KG, Forman SJ, editors. Hematopoietic cell transplantation. USA: Blackwell Science; 1999.p.305-15. google scholar
- 21. Hagglund H, Boström L, Remberger M, Ljungman P, Nilsson B, Ringden O. Risk factors for acute graft versus host disease in 219 consecutive HLA identical bone marrow transplant recipients. Bone Marrow Transplant 1995;16(6):747-53. google scholar
- 22. Tseng LH, Lin MT, Hansen JA, Gooley T, Pei J, Smith AG et al. Correlation between Disparity for the Minor Histocompatibility Antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation. Blood 1999; 94(8):2911-4. google scholar
- 23. Wang W, Huang H, Halagan M, Vierra-Green C, Heuer M, Brelsford JE, et al. Chromosome Y-encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant. Blood Adv 2018;9;2(19):2419-29. google scholar
- 24. Goulmy E. Minor histocompatibility antigens: allo target molecules for tumor-specific immunotherapy. Cancer J 2004;10(1):1-7. google scholar
- 25. Hambach L, Goulmy E. Immunotherapy of cancer through targeting of minor histocompatibility antigens. Curr Opin Immunol 2005;17(2):202-10. google scholar
- 26. Gustincich S, Manfiolett G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Bio Techniques 1991;11(3):298-302. google scholar
Details
| Primary Language | English |
|---|---|
| Journal Section | Research Articles |
| Authors | |
| Project Number | 292/05012005 |
| Publication Date | November 16, 2022 |
| Submission Date | June 16, 2022 |
| Published in Issue | Year 2022 Volume: 5 Issue: 3 |
