PMID- 10371359
OWN - NLM
STAT- MEDLINE
DCOM- 19990721
LR  - 20191103
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 5
IP  - 2
DP  - 1999
TI  - HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and 
      -DRB1 alleles: impact of serological vs. DNA typing for HLA-A and -B loci.
PG  - 77-85
AB  - High incidences of graft failure, graft-vs.-host disease (GVHD), and serious 
      infections following unrelated donor (URD) marrow transplantation, despite 
      apparent human leukocyte antigen (HLA) identity, may reflect the presence of 
      molecular disparities, including those for HLA-C alleles between the patient and 
      the URD. The level of these disparities could be significant, because as many as 
      42 alleles are currently known for HLA-C locus. We studied 84 patients and 251 
      potential URDs to evaluate 1) the extent of HLA-C disparity between the patient 
      and the URD identified by serology for HLA-A and -B and by DNA typing for -DRB1 
      and 2) the level of HLA-C disparity between patients and URDs matched by 
      high-resolution DNA typing for HLA-A, -B, and -DRB1. The DNA typing was performed 
      at the Memorial Sloan Kettering Cancer Center, and the serotyping was provided by 
      the registries. Of 251 URDs matched by HLA-A and -B serology and -DRB1 
      (sA_sB_dnaDRB1 ); 94, 75, and 82 were 6/6, 5/6, and 4/6 matches, respectively. Of 
      94 sA_sB_dnaDRB1 6/6 URDs, 51 (54.3%) were matched for both HLA-C alleles. In 
      contrast, 31 (41.3%) 5/6 (p=0.12) and 15 (18.3%) 4/6 (p < 0.01) sA_sB_dnaDRB1 
      URDs were matched for both HLA-C alleles. Following DNA typing for HLA-A and -B, 
      52 (55.3%) of 94 6/6, 30 (40%) of 75 5/6, and 25 (30.5%) of 82 4/6 sA_sB_dnaDRB1 
      URDs remained 6/6, 5/6, and 4/6 matches at the DNA level (dnaA_B_DRB1). HLA-C 
      disparities continued to exist in the dnaA_B_DRB1 URD group. Of 54 dnaA_B_DRB1 
      6/6 URDs, 41 (75.9%) were matched for both HLA-C alleles. Only 45.3% of the 5/6 
      (p=0.01) and 22.2% of the 4/6 (p < 0.01) dnaA_B_DRB1 URDs were matched for both 
      HLA-C alleles. In the 6/6 category, the frequency of HLA-C matching improved 
      (75.9 vs. 54.3%; p=0.01) following DNA matching for HLA-A and -B. In comparison 
      to mismatching for HLA-B locus, mismatching for either HLA-DRB1 or -A resulted in 
      a lower odds ratio for HLA-C disparity. The presence of a common haplotype in the 
      sA_sB_dnaDRBl (p=0.06) URD category improved the level of HLA-C matching. We 
      identified alleles that are associated with high (B*1501, B*4402, B*5101, 
      DRB1*0101, A*0201, A*1101, A*2301, and A*3201) or low (B*0702, B*0801, B*1302, 
      B*3502, DRB1*0301, DRB1*1104, A*0101, A*3001, and A*6801) probability of HLA-C 
      disparity. Overall, sA_sB_dnaDRB1 as well as dnaA_B_DRB1 matched URDs for 
      non-Caucasian patients were more likely to have HLA-C disparity in comparison to 
      the matched URDs of Caucasian patients. However, a high incidence of HLA-C 
      disparities was identified even in the URDs for Caucasian patients. Whether the 
      disparities demonstrated by this study contribute to the higher immunological 
      complications noted following URD bone marrow transplantation is unclear. Outcome 
      analysis and studies aimed at understanding the functional role of HLA-C may 
      provide an answer.
FAU - Prasad, V K
AU  - Prasad VK
AD  - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 
      10021, USA.
FAU - Kernan, N A
AU  - Kernan NA
FAU - Heller, G
AU  - Heller G
FAU - O'Reilly, R J
AU  - O'Reilly RJ
FAU - Yang, S Y
AU  - Yang SY
LA  - eng
GR  - P01 CA23766/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*03:01 antigen)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - *Bone Marrow Transplantation
MH  - DNA/analysis
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - HLA-DR Antigens/genetics/immunology
MH  - HLA-DRB1 Chains
MH  - *Histocompatibility Testing/methods
MH  - Humans
MH  - *Transplantation Immunology
EDAT- 1999/06/17 00:00
MHDA- 1999/06/17 00:01
CRDT- 1999/06/17 00:00
PHST- 1999/06/17 00:00 [pubmed]
PHST- 1999/06/17 00:01 [medline]
PHST- 1999/06/17 00:00 [entrez]
AID - S1083879199500402 [pii]
AID - 10.1053/bbmt.1999.v5.pm10371359 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 1999;5(2):77-85. doi: 
      10.1053/bbmt.1999.v5.pm10371359.