A high degree of HLA disparity arises from limited allelic diversity: analysis of 1775 unrelated bone marrow transplant donor-recipient pairs.
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.
Hurley
Carolyn Katovich
CK
Department of Oncology, Georgetown University, Washington, DC, USA. hurleyc@georgetown.edu
Fernandez-Vina
Marcelo
M
Hildebrand
William H
WH
Noreen
Harriet J
HJ
Trachtenberg
Elizabeth
E
Williams
Thomas M
TM
Baxter-Lowe
Lee Ann
LA
Begovich
Ann B
AB
Petersdorf
Effie
E
Selvakumar
Annamalai
A
Stastny
Peter
P
Hegland
Janet
J
Hartzman
Robert J
RJ
Carston
Michael
M
Gandham
Sharavi
S
Kollman
Craig
C
Nelson
Gene
G
Spellman
Stephen
S
Setterholm
Michelle
M
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
D006680:HLA Antigens; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I