An Overview of HLA Typing for Hematopoietic Stem Cell Transplantation

  • Katy Latham
  • Ann-Margaret Little
  • J. Alejandro Madrigal
Part of the Methods in Molecular Biology book series (MIMB, volume 1109)


The selection of a related or an unrelated hematopoietic stem cell donor for a patient requires accurate matching of human leukocyte antigen (HLA) genes in order to maximize the beneficial effects of the transplant. There are various different factors a laboratory must consider in order to achieve an HLA type including the number of samples being processed, level of resolution to be achieved, cost of providing the various tests, and turnaround time required. Each method has its advantages and disadvantages, and in most laboratories, a combination of methods may be used.

Key words




Dr. Raymond Fernando and Mr. Franco Tavarozzi are thanked for providing Fig. 2.


  1. 1.
    Warrens A, Lechler R (eds) (2000) HLA in health and disease. Academic, London, pp 139–146Google Scholar
  2. 2.
    Mallal S, Nolan D, Witt C et al (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir. Lancet 359:727–732PubMedCrossRefGoogle Scholar
  3. 3.
    Abi-Rached L, Jobin MJ, Kulkarni S et al (2011) The shaping of modern human immune systems by multiregional admixture with archaic humans. Science 334:89–94PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Klein K (1986) Natural history of the major histocompatibility complex. Wiley, Toronto, ONGoogle Scholar
  5. 5.
    Cao K, Chopek M, Fernandez-Vina MA (1999) High and intermediate resolution DNA typing systems for class I HLA-A, B, C genes by hybridization with sequence-specific oligonucleotide probes (SSOP). Rev Immunogenet 1:177–208PubMedGoogle Scholar
  6. 6.
    Trajanoski D, Fidler SJ (2012) HLA typing using bead-based methods. Methods Mol Biol 882:47–65PubMedCrossRefGoogle Scholar
  7. 7.
    Olerup O, Zetterquist H (1992) 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 39:225–235PubMedCrossRefGoogle Scholar
  8. 8.
    Bunce M, O’Neill CM, Barnardo MC et al (1995) Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens 46:355–367PubMedCrossRefGoogle Scholar
  9. 9.
    Newton CR, Graham A, Heptinstall LE et al (1989) Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res 17:2503–2516PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    van der Vlies SA, Voorter CE, van den Berg-Loonen EM (1998) A reliable and efficient high resolution typing method for HLA-C using sequence-based typing. Tissue Antigens 52:558–568PubMedCrossRefGoogle Scholar
  11. 11.
    Turner S, Ellexson ME, Hickman HD et al (1998) Sequence-based typing provides a new look at HLA-C diversity. J Immunol 161:1406–1413PubMedGoogle Scholar
  12. 12.
    Swelsen WT, Voorter CE, van den Berg-Loonen EM (2005) Sequence-based typing of the HLA-A10/A19 group and confirmation of a pseudogene coamplified with A*3401. Hum Immunol 66:535–542PubMedCrossRefGoogle Scholar
  13. 13.
    Kotsch K, Wehling J, Blasczyk R (1999) Sequencing of HLA class II genes based on the conserved diversity of the non-coding regions: sequencing based typing of HLA-DRB genes. Tissue Antigens 53:486–497PubMedCrossRefGoogle Scholar
  14. 14.
    Sayer DC, Goodridge DM, Christiansen FT (2004) Assign 2.0: software for the analysis of Phred quality values for quality control of HLA sequencing-based typing. Tissue Antigens 64:556–565PubMedCrossRefGoogle Scholar
  15. 15.
    Rozemuller EH, Tilanus MG (2000) Bioinformatics: analysis of HLA sequence data. Rev Immunogenet 2:492–517PubMedGoogle Scholar
  16. 16.
    Shiina T, Suzuki S, Ozaki Y et al (2012) Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers. Tissue Antigens 80:305–316PubMedCrossRefGoogle Scholar
  17. 17.
    Lind C, Ferriola D, Mackiewicz K et al (2012) Filling the gaps—the generation of full genomic sequences for 15 common and well-documented HLA class I alleles using next-generation sequencing technology. Hum Immunol 74:318–324Google Scholar
  18. 18.
    Liu L, Li Y, Li S et al (2012) Comparison of next generation sequencing systems. J Biomed Biotechnol 2012:251364. doi: 10.1155/2012/251364 PubMedCentralPubMedGoogle Scholar
  19. 19.
    Moonsamy PV, Williams T, Bonella P et al (2013) High throughput HLA genotyping using 454 sequencing and the Fluidigm Access Array™ system for simplified amplicon library preparation. Tissue Antigens 81:141–149PubMedCrossRefGoogle Scholar
  20. 20.
    Eid J, Fehr A, Gray J et al (2009) Real-time DNA sequencing from single polymerase molecules. Science 323:133–138PubMedCrossRefGoogle Scholar
  21. 21.
    Maitra RD, Kim J, Dunbar WB (2012) Recent advances in nanopore sequencing. Electrophoresis 33:3418–3428PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Valcarcel D, Sirra J, Wang T et al (2011) One antigen mismatched related versus HLA matched unrelated donor haematopoietic stem cell transplantation in adults with acute leukemia: center for International Blood and Marrow Transplant Research results in the ERA or molecular HLA typing. Biol Blood Marrow Transplant 17:640–648PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Buchler T, Gallardo D, Rodriguez-Luaces M, Pujal JM, Granena A (2002) Frequency of HLA-DPB1 disparities detected by reference strand-mediated conformation analysis in HLA-A, -B, and -DRB1 matched siblings. Hum Immunol 63:139–142PubMedCrossRefGoogle Scholar
  24. 24.
    Bioinformatics.NMDP.Org. Policies (
  25. 25.
    Flomenberg N, Baxter-Lowe LA, Confer D et al (2004) Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood 104:1923–1930PubMedCrossRefGoogle Scholar
  26. 26.
    Petersdorf EW, Anasetti C, Martin PJ et al (2004) Limits of HLA mismatching in unrelated hematopoietic cell transplantation. Blood 104:2976–2980PubMedCrossRefGoogle Scholar
  27. 27.
    Shaw BE, Potter MN, Mayor NP et al (2003) The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation. Bone Marrow Transplant 31:1001–1008PubMedCrossRefGoogle Scholar
  28. 28.
    Fleischauer K, Shaw BE, Gooley T et al (2012) Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated donor haemopoietic cell transplantation: a retrospective study. Lancet Oncol 13:366–374CrossRefGoogle Scholar
  29. 29.
    Bone Marrow Donors Worldwide ( Accessed Feb 2013
  30. 30.
    Eapen M, Klein JP, Sanz GF et al (2011) Effect of donor–recipient HLA matching at HLA A, B, C, andDRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol 12:1214–1221PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, Marsh SGE (2011) The IMGT/HLA database. Nucleic Acids Res 39:1171–1176CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, New York 2014

Authors and Affiliations

  • Katy Latham
    • 1
  • Ann-Margaret Little
    • 2
  • J. Alejandro Madrigal
    • 1
  1. 1.Anthony Nolan Research InstituteUniversity College LondonLondonUK
  2. 2.Histocompatibility and Immunogenetics, Greater Glasgow and ClydeGartnavel General HospitalGlasgowUK

Personalised recommendations