title: A high degree of HLA disparity arises from limited allelic diversity: analysis of 1775 unrelated bone marrow transplant donor-recipient pairs.
abstract: The allelic diversity and associated human leukocyte antigen (HLA) disparity of 1775 bone marrow recipients and their unrelated donors, matched for six of six (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A, -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most (>66%) of the predominantly Caucasian study population carried one or two of five to seven common alleles at each HLA locus. In spite of this limited diversity, 29% of the six of six antigen-matched transplants carried allele mismatches at HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89% carried mismatches at other HLA loci, predominantly at DP loci. The substantially greater than expected HLA allelic disparity between donor and recipient suggests extensive haplotypic diversity and underscores the importance of enhancing approaches to mitigate the deleterious effect of HLA mismatches.
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC, USA. hurleyc@georgetown.edu
authors.forename: Carolyn Katovich
authors.initials: CK
authors.lastname: Hurley
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: Harriet J
authors.initials: HJ
authors.lastname: Noreen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Williams
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: Ann B
authors.initials: AB
authors.lastname: Begovich
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Annamalai
authors.initials: A
authors.lastname: Selvakumar
authors.forename: Peter
authors.initials: P
authors.lastname: Stastny
authors.forename: Janet
authors.initials: J
authors.lastname: Hegland
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hartzman
authors.forename: Michael
authors.initials: M
authors.lastname: Carston
authors.forename: Sharavi
authors.initials: S
authors.lastname: Gandham
authors.forename: Craig
authors.initials: C
authors.lastname: Kollman
authors.forename: Gene
authors.initials: G
authors.lastname: Nelson
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Michelle
authors.initials: M
authors.lastname: Setterholm
mesh_terms: D000483:Alleles; D016026:Bone Marrow Transplantation / Q000276:immunology*; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I