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HLA Typing and Its Influence on Organ Transplantation

  • Stephen Sheldon
  • Kay Poulton
Part of the Methods In Molecular Biology™ book series (MIMB, volume 333)

Abstract

Human leukocyte antigen (HLA) molecules are expressed on almost all nucleated cells, and they are the major molecules that initiate graft rejection. There are three classical loci at HLA class I: HLA-A, -B, and -Cw, and five loci at class II: HLA-DR, -DQ, -DP, -DM, and -DO. The system is highly polymorphic, there being many alleles at each individual locus. Three methods for HLA typing are described in this chapter, including serological methods and the molecular techniques of sequence-specific priming (SSP) and sequence-specific oligonucleotide probing (SSOP). The influence of HLA matching on solid organ and bone marrow transplantation is also described. HLA matching has had the greatest clinical impact in kidney and bone marrow transplantation, where efforts are made to match at the HLA-A, -B, and -DR loci. In heart and lung transplantation, although studies have shown it would be an advantage to match especially at the DR locus, practical considerations (ischemic times, availability of donors, clinical need of recipients) make this less of a consideration. Corneal grafts are not usually influenced by HLA matching, unless being transplanted into a vascularized (or inflamed) bed.

Key Words

HLA molecules crossmatching tissue-typing serology 

References

  1. 1.
    Dausset J. (1958) Iso-leuco anticorps. Acta Haematol. 20, 156–166.CrossRefPubMedGoogle Scholar
  2. 2.
    Van Rood J. J. and Van Leeuwen A. (1963) Leucocyte grouping. A method and its applications. J. Clin. Invest. 42, 1382–1390.CrossRefGoogle Scholar
  3. 3.
    Payne R., Trip M., Weigle J., Bodmer W., and Bodmer J. (1964) A new leukocyte iso-antigen system in man. Cold Spring Harbour Symp. 29, 285–295.Google Scholar
  4. 4.
    Snell G. D. (1948) Methods for the study of histocompatibility genes. J. Genet. 49, 87–108.CrossRefPubMedGoogle Scholar
  5. 5.
    Gorer P. A. (1937) The genetic and antigenic basis for tumor transplantation. J. Pathol. Bacteriol. 44, 691–697.CrossRefGoogle Scholar
  6. 6.
    Marsh S. G. E., Albert E. D., Bodmer W. F., et al. (2002) Nomenclature for factors of the HLA system 2002. Tissue Antigens 60, 407–464.CrossRefPubMedGoogle Scholar
  7. 7.
    Terasaki P. I. and McClelland J. D. (1964) Microdroplet assay of human cytotoxins. Nature 204, 998–1000.CrossRefPubMedGoogle Scholar
  8. 8.
    Vartdal F., Gaudernack G., Funderud S., et al. (1986) HLA class I and II typing using cells positively selected from blood by immunomagnetic isolation-a fast and reliable technique. Tissue Antigens 28, 301–312.CrossRefPubMedGoogle Scholar
  9. 9.
    Olerup O. and Zetterquist H. (1993) HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours; an alternative to serological DR typing in clinical practice including donor recipient matching in cadaveric transplantation. Tissue Antigens 39, 225–235.CrossRefGoogle Scholar
  10. 10.
    Bignon J. D., Fernandez-Vina M. A., Cheneau M. L., et al. (1997) HLA DNA class II typing by PCR-SSOP: 12th International Histocompatibility Workshop experience, in HLA Genetic Diversity of HLA Functional and Medical Implication, Proceedings of the 12th International Histocompatibility Workshop, Vol. 1 (Charron D. ed.), EDK Press, Paris, pp. 21–25.Google Scholar
  11. 11.
    Kennedy L. J., Poulton K. V., Thomson W., et al. (1997) HLA class I DNA typing using sequence specific oligonucleotide probes (SSOP), in HLA Genetic Diversity of HLA Functional and Medical Implication, Proceedings of the 12th International Histocompatibility Workshop, Vol. 1 (Charron D., ed.), EDK Press, Paris, pp. 216–225.Google Scholar
  12. 12.
    Cao K., Chopek M., and Fernandez-Vina M. A. (1999) High and intermediate resolution DNA typing systems for class I HLA-A, B, C genes by hybridisation with sequence specific oligonucleotide probes (SSOP). Rev, Immunogenet. 1, 177–208.Google Scholar
  13. 13.
    Buyse I., Decorte R., Baens M., et al. (1993) Rapid DNA typing of class II HLA antigens using the polymerase chain reaction and reverse dot blot hybridisation. Tissue Antigens 41, 1–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Patel R. and Terasaki P. I. (1969) Significance of the positive crossmatch test in kidney transplantation. N. Engl. J. Med. 280(14), 735–739.CrossRefPubMedGoogle Scholar
  15. 15.
    Opelz G., Wujciak T., Dohler B., Scherer S., and Mytilineos J. (1999) HLA compatibility and organ transplant survival. Rev. Immunogenet. 1, 334–342.PubMedGoogle Scholar
  16. 16.
    Dyer P. A., Johnson R. W., Martin S., et al. (1989) Evidence that matching for HLA antigens significantly increases transplant survival in 1001 renal transplants performed in the northwest region of England. Transplantation 48(1), 131–135.CrossRefPubMedGoogle Scholar
  17. 17.
    Festenstein H., Doyle P., and Holmes J. (1986) Long-term follow-up in London Transplant Group recipients of cadaver renal allografts. The influence of HLA matching on transplant outcome. N. Engl. J. Med. 314(1), 7–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Ayoub G. and Terasaki P. (1982) HLA-DR matching in multicenter, single-typing laboratory data. Transplantation 33(5), 515–517.CrossRefPubMedGoogle Scholar
  19. 19.
    Starzl T. E., Eliasziw M., Gjertson D. J., et al. (1997) HLA and cross-reactive group matching for cadaveric kidney allocation. Transplantation 64, 983–991.CrossRefPubMedGoogle Scholar
  20. 20.
    Mange K. C., Cherikh W. S., Maghirang J., and Bloom R. D. (2001) A comparison of the survival of shipped and locally transplanted cadaveric renal allografts. N. Engl. J. Med.. 34, 1237–1242.CrossRefGoogle Scholar
  21. 21.
    Oniscu G. C., Plant W., Pocock P., and Forsythe J. L. (2002) Scotland-Northern Ireland Alliance in conjunction with UK Transplant, United Kingdom. Does a kidney-sharing alliance have to sacrifice cold ischemic time for better HLA matching? Transplantation 73, 1647–1652.CrossRefPubMedGoogle Scholar
  22. 22.
    Eichhorn E. J. (2001) Prognosis determination in heart failure. Am. J. Med. 110(Suppl. 7A), 14s–36s.CrossRefPubMedGoogle Scholar
  23. 23.
    Large S. R. (2002) Is there a crisis in cardiac transplantation? Lancet 359, 803–803.CrossRefPubMedGoogle Scholar
  24. 24.
    Sheldon S., Yonan N. A., Aziz T. N., et al. (1999) The influence of histocompatibility on graft rejection and graft survival within a single centre population of heart transplant recipients. Transplantation 68, 515–519.CrossRefPubMedGoogle Scholar
  25. 25.
    Smith J. D., Rose M. L., Pomerance A., Burke M., and Yacoub M. H. (1995) Reduction of cellular rejection and increase in longer-term survival after heart transplantation after HLA-DR matching. Lancet 346(8986), 1318–1322.CrossRefPubMedGoogle Scholar
  26. 26.
    Opelz G. and Wujciak T. (1994) The influence of HLA compatibility on graft survival after heart transplantation. N. Engl. J. Med. 330(12), 816–819.CrossRefPubMedGoogle Scholar
  27. 27.
    Kerman R. H., Van-Buren C. T., Lewis R. M., Frazier O. H., Cooley D., and Kahan B. D. (1988) The impact of HLA A, B, and DR blood transfusions and immune responder status on cardiac allograft recipients treated with cyclosporine. Transplantation 45(2), 333–337.CrossRefPubMedGoogle Scholar
  28. 28.
    Schulman L. L., Weinberg A. D., McGregor C., Galantowicz M. E., Suciu-Foca N. M., and Itescu S. (1998) Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am. J. Respir. Crit. Care Med. 157, 1833–1837.PubMedGoogle Scholar
  29. 29.
    Schulman L. L., Weinberg A. D., McGregor C., Suciu-Foca N. M., and Itescu S. (2001) Influence of donor and recipient HLA locus mismatching on the development of obliterative bronchiolitis after lung transplantation. Am. J. Respir. Crit. Care Med. 163, 437–442.PubMedGoogle Scholar
  30. 30.
    van den Berg J. W., Hepkema B. G., Geertsma A., et al. (2001) Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches. Transplantation 71(3), 368–373.CrossRefPubMedGoogle Scholar
  31. 31.
    Chalermskulrat W., Neuringer I. P., Schmitz J. L., et al. (2003) Human leukocyte antigen mismatches predispose to the severity of bronchiolitis obliterans syndrome after lung transplantation. Chest 123(6), 1825–1831.CrossRefPubMedGoogle Scholar
  32. 32.
    Donaldson P., Underhill J., Doherty D., et al. (1993) Influence of human leukocyte antigen matching on liver allograft survival and rejection: “the dualistic effect.” Hepatology 17, 1008–1015.CrossRefPubMedGoogle Scholar
  33. 33.
    Niederkorn J. Y. (2002) Immune privilege in the anterior chamber of the eye. Crit. Rev. Immunol. 22, 13–46.PubMedGoogle Scholar
  34. 34.
    Bartels M. C., Doxiadis I. N., Colen T. P., and Beekhuis W. H. (2003) Longterm outcome in high-risk corneal transplantation and the influence of HLA-A and HLA-B matching. Cornea 22, 552–556.CrossRefPubMedGoogle Scholar
  35. 35.
    Charron D. (2003) Immunogenomics of hematopoietic stem cell transplantation. Transfus. Clin. Biol. 10, 156–158.CrossRefPubMedGoogle Scholar
  36. 36.
    Hurley C. K., Wade J. A., Oudshoorn M., et al, on behalf of the Quality Assurance and Donor Registries Working Groups of the World Marrow Donor Association. (1999) A special report: histocompatibility testing guidelines for haematopoietic stem cell transplantation using volunteer donors. Hum. Immunol. 60, 347–360.CrossRefPubMedGoogle Scholar
  37. 37.
    Mickelson E. M., Petersdorf E., Anasetti C., Martin P., and Hansen J. A. (1998) HLA matching in haematopoietic cell transplantation, in HLA 1998 (Gjertson D. W. and Terasaki P. L., eds.), American Society for Histocompatibility and Immunogenetics, Lenexa, KS, pp. 47–56.Google Scholar
  38. 38.
    Gaudieri S., Longman-Jacobson N., Tay G. K., and Dawkins R. L. (2001) Sequence analysis of the MHC class I region reveals the basis of the genomic matching technique. Hum. Immunol. 62(3), 279–285.CrossRefPubMedGoogle Scholar
  39. 39.
    Petersdorf E. W., Hansen J. A., Martin P. J., et al. (2001) Major histocompatibility complex class I alleles and antigens in haematopoietic cell transplantation. N. Engl. J. Med. 345, 1794–1800.CrossRefPubMedGoogle Scholar
  40. 40.
    Kollman C., Howe C. W. S., Anasetti C., et al. (2001) Donor characteristics as risk factors after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 97(7), 2043–2051.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Stephen Sheldon
    • 1
  • Kay Poulton
    • 1
  1. 1.Transplantation Laboratory, Central Manchester and ManchesterChildren’s University Hospitals NHS Trust, Manchester Royal InfirmaryManchesterEngland

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