Blood Journal
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Molecular Typing Shows a High Level of HLA Class I Incompatibility in Serologically Well Matched Donor/Patient Pairs: Implications for Unrelated Bone Marrow Donor Selection

  1. Iain Scott,
  2. John O’Shea,
  3. Mike Bunce,
  4. Jean-Marie Tiercy,
  5. J. Rafael Argüello,
  6. Helen Firman,
  7. John Goldman,
  8. H. Grant Prentice,
  9. Ann-Margaret Little, and
  10. J. Alejandro Madrigal
  1. 1 From the Anthony Nolan Research Institute and the Department of Haematology, The Royal Free Hospital, London, UK; the Department of Haematology, Imperial College School of Medicine, London, UK; The Nuffield Department of Surgery, Oxford Transplant Centre, Churchill Hospital, Oxford, UK; and the Transplantation Immunology Unit, Hopital Cantonal Universitaire, Geneva, Switzerland.


In comparison with HLA-matched sibling bone marrow transplants, unrelated donor transplants are associated with increased graft-versus-host disease and graft failure. This is likely in part due to HLA incompatibilities not identified by current matching strategies. High resolution DNA-based typing methods for HLA class II loci have improved donor selection and treatment outcome in unrelated donor bone marrow transplantation. By using DNA-based typing methods for HLA-A and -B on a cohort of 100 potential bone marrow donor/patient pairs, we find that serological typing for HLA class I is limited in its ability to identify incompatibilities in unrelated pairs. Furthermore, the incompatibilities identified are associated with the presence at high frequency of alloreactive cytotoxic T-lymphocyte precursors. DNA typing also indicates that HLA-C mismatches are common in HLA-A and -B serologically matched pairs. Such mismatches appear to be significantly less immunogenic with respect to cytotoxic T-lymphocyte recognition, but are expected to influence natural killer cell activity. Thus, improved resolution of HLA class I shows many previously undisclosed mismatches that appear to be immunologically functional. Use of high resolution typing methods in routine matching is expected to improve unrelated donor selection and transplant outcome.

  • Submitted April 22, 1998.
  • Accepted August 13, 1998.
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