PMID- 17378697
OWN - NLM
STAT- MEDLINE
DCOM- 20070404
LR  - 20220408
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 4
IP  - 1
DP  - 2007 Jan
TI  - MHC haplotype matching for unrelated hematopoietic cell transplantation.
PG  - e8
LID - e8
AB  - BACKGROUND: Current criteria for the selection of unrelated donors for 
      hematopoietic cell transplantation (HCT) include matching for the alleles of each 
      human leukocyte antigen (HLA) locus within the major histocompatibility complex 
      (MHC). Graft-versus-host disease (GVHD), however, remains a significant and 
      potentially life-threatening complication even after HLA-identical unrelated HCT. 
      The MHC harbors more than 400 genes, but the total number of transplantation 
      antigens is unknown. Genes that influence transplantation outcome could be 
      identified by using linkage disequilibrium (LD)-mapping approaches, if the 
      extended MHC haplotypes of the unrelated donor and recipient could be defined. 
      METHODS AND FINDINGS: We isolated DNA strands extending across 2 million base 
      pairs of the MHC to determine the physical linkage of HLA-A, -B, and -DRB1 
      alleles in 246 HCT recipients and their HLA-A, -B, -C, -DRB1, -DQB1 
      allele-matched unrelated donors. MHC haplotype mismatching was associated with a 
      statistically significantly increased risk of severe acute GVHD (odds ratio 4.51; 
      95% confidence interval [CI], 2.34-8.70, p < 0.0001) and with lower risk of 
      disease recurrence (hazard ratio 0.45; 95% CI, 0.22-0.92, p = 0.03). CONCLUSIONS: 
      The MHC harbors genes that encode unidentified transplantation antigens. The 
      three-locus HLA-A, -B, -DRB1 haplotype serves as a proxy for GVHD risk among 
      HLA-identical transplant recipients. The phasing method provides an approach for 
      mapping novel MHC-linked transplantation determinants and a means to decrease 
      GVHD-related morbidity after HCT from unrelated donors.
FAU - Petersdorf, Effie W
AU  - Petersdorf EW
AD  - Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, United States of America. epetersd@fhcrc.org
FAU - Malkki, Mari
AU  - Malkki M
FAU - Gooley, Ted A
AU  - Gooley TA
FAU - Martin, Paul J
AU  - Martin PJ
FAU - Guo, Zhen
AU  - Guo Z
LA  - eng
GR  - CA18029/CA/NCI NIH HHS/United States
GR  - P01 CA018029/CA/NCI NIH HHS/United States
GR  - AI33484/AI/NIAID NIH HHS/United States
GR  - P01 AI033484/AI/NIAID NIH HHS/United States
GR  - R01 CA100019/CA/NCI NIH HHS/United States
GR  - AI49213/AI/NIAID NIH HHS/United States
GR  - U24 AI049213/AI/NIAID NIH HHS/United States
GR  - CA100019/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Genetic Linkage
MH  - Graft vs Host Disease
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-B Antigens/genetics/immunology
MH  - HLA-DR Antigens/genetics/immunology
MH  - HLA-DRB1 Chains
MH  - Haplotypes/*genetics
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility/*genetics/*immunology
MH  - Humans
MH  - Infant
MH  - Major Histocompatibility Complex/*genetics/*immunology
MH  - Male
MH  - Middle Aged
MH  - Mortality
MH  - Recurrence
MH  - Treatment Outcome
PMC - PMC1796628
COIS- Competing Interests: EWP and ZG have applied for a US non-provisional 111(a) 
      patent for the haplotyping method, serial number 10/843,985. The remaining 
      authors have no conflict of interest.
EDAT- 2007/03/24 09:00
MHDA- 2007/04/05 09:00
PMCR- 2007/01/30
CRDT- 2007/03/24 09:00
PHST- 2006/06/09 00:00 [received]
PHST- 2006/11/06 00:00 [accepted]
PHST- 2007/03/24 09:00 [pubmed]
PHST- 2007/04/05 09:00 [medline]
PHST- 2007/03/24 09:00 [entrez]
PHST- 2007/01/30 00:00 [pmc-release]
AID - 06-PLME-RA-0442R3 [pii]
AID - 10.1371/journal.pmed.0040008 [doi]
PST - ppublish
SO  - PLoS Med. 2007 Jan;4(1):e8. doi: 10.1371/journal.pmed.0040008.