HLA-DRB1,3,4,5 and-DQB1 allele frequencies and HLA-DR/DQ linkage disequilibrium of 231 German caucasoid patients and their corresponding 821 potential unrelated stem cell transplants
HUMAN IMMUNOLOGY
Authors: Knipper, AJ; Hakenberg, P; Enczmann, J; Kuhrober, A; Kiesel, U; Kogler, G; Wernet, P
Abstract
Allelic matching within the HLA-DRB1 and -DQB1 loci significantly improves thr clinical outcome of hematopoietic stem cell transplantation. Consequently, allelic typing of these loci is strongly recommended for the unrelated stem cell donor selection. In this study, the HLA-DRB1,3,4,5 and -DQB1 alleles of 231 patients and their corresponding 821 nonrandom potential stem cell donors were determined to define compatible donor/recipient pairs. Highly accurate HLA typing data were achieved by PCR-SSOP and a combination of group specific PCR-SSP and subsequent sequencing-based typing of nearly the whole second exon of each locus. The alleles DRB1*07, *09 and *10 were analyzed by PCR-reverse dot blot hybridization instead of sequencing. Additionally, DRB1 homozygosity was verified by temperature gradient gel electrophoresis. The identified 2104 HLA-DRB1 and HLA-DQB1 alleles as well as data on HLA-DRB3, -DRB4, and -DRB5 alleles were applied to a statistical program and absolute and relative delta values of DR/DQ linkages were calculated. The achieved data on the HLA-DRB1 allele distribution and on DR/DQ associations in terms of subtypes significantly ensure the typing reliability, since rare allele combinations will result in further investigations. Furthermore, detailed data on the DR/DQ allele associations allow estimations of thr number of HLA-A, -B, and -DR marched unrelated stem cell donors necessary for the identification of DRB and DQB subtype identical donors. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.
Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation
BLOOD
Authors: Fernandez-Vina, Marcelo A.; Klein, John P.; Haagenson, Michael; Spellman, Stephen R.; Anasetti, Claudio; Noreen, Harriet; Baxter-Lowe, Lee Ann; Cano, Pedro; Flomenberg, Neal; Confer, Dennis L.; Horowitz, Mary M.; Oudshoorn, Machteld; Petersdorf, Effie W.; Setterholm, Michelle; Champlin, Richard; Lee, Stephanie J.; de Lima, Marcos
Abstract
A single mismatch in highly expressed HLA-A, -B, -C, and -DRB1 loci (HEL) is associated with worse outcomes in hematopoietic stem cell transplantation, while less is known about the cumulative impact of mismatches in the lesser expressed HLA loci DRB3/4/5, DQ, and DP (LEL). We studied whether accumulation of LEL mismatches is associated with deleterious effects in 3853 unrelated donor transplants stratified according to number of matches in the HEL. In the 8/8 matched HEL group, LEL mismatches were not associated with any adverse outcome. Mismatches at HLA-DRB1 were associated with occurrence of multiple LEL mismatches. In the 7/8 HEL group, patients with 3 or more LEL mismatches scored in the graft-versus-host vector had a significantly higher risk of mortality (1.45 and 1.43) and transplant-related mortality (1.68 and 1.54) than the subgroups with 0 or 1 LEL mismatches. No single LEL locus had a more pronounced effect on clinical outcome. Three or more LEL mismatches are associated with lower survival after 7/8 HEL matched transplantation. Prospective evaluation of matching for HLA-DRB3/4/5, -DQ, and -DP loci is warranted to reduce posttransplant risks in donor-recipient pairs matched for 7/8 HEL.