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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4864-4871
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
Iain Scott,
John O'Shea,
Mike Bunce,
Jean-Marie Tiercy,
J. Rafael Argüello,
Helen Firman,
John Goldman,
H. Grant Prentice,
Ann-Margaret Little, and
J. Alejandro Madrigal
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.
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