title: 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.
abstract: 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.
authors.affiliation: Anthony Nolan Research Institute and the Department of Haematology, The Royal Free Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: O'Shea
authors.forename: M
authors.initials: M
authors.lastname: Bunce
authors.forename: J M
authors.initials: JM
authors.lastname: Tiercy
authors.forename: J R
authors.initials: JR
authors.lastname: Argüello
authors.forename: H
authors.initials: H
authors.lastname: Firman
authors.forename: J
authors.initials: J
authors.lastname: Goldman
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: A M
authors.initials: AM
authors.lastname: Little
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
mesh_terms: D020137:Base Pair Mismatch; D001853:Bone Marrow / Q000737:chemistry / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004247:DNA / Q000032:analysis; D015234:HLA-A Antigens / Q000032:analysis / Q000235:genetics; D015235:HLA-B Antigens / Q000032:analysis / Q000235:genetics; D015236:HLA-C Antigens / Q000032:analysis / Q000235:genetics; D006648:Histocompatibility / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D019520:Living Donors; D009693:Nucleic Acid Hybridization / Q000379:methods; D016133:Polymerase Chain Reaction
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D004247:DNA