Impact of highly conserved HLA haplotype on acute graft-versus-host disease

Satoko Morishima, Seishi Ogawa, Aiko Matsubara, Takakazu Kawase, Yasuhito Nannya, Koichi Kashiwase, Masahiro Satake, Hiroo Saji, Hidetoshi Inoko, Shunichi Kato, Yoshihisa Kodera, Takehiko Sasazuki, Yasuo Morishima

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Abstract

Although the effects of human leukocyte antigen (HLA) locus matching on clinical outcome in unrelated hematopoietic stem cell transplantations have been characterized, the biologic implications of HLA haplotypes have not been defined. We demonstrated the genetic fixity of Japanese conserved extended haplotypes by multi-single nucleotide polymorphism analysis in 1810 Japanese donor-recipient pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially completely conserved at least in the 3.3-Mb HLA region from HLA-A to -DPB1, and extended far beyond HLA-A. The risk of acute graft-versus-host disease (GVHD) of these HLA haplotypes was assessed with multivariate Cox regression in 712 patients transplanted from HLA fully (HLA-A, B, C, DRB1, DQB1, and DPB1) matched unrelated donors. HP-P2 itself reduced the risk of grade 2 to 4 acute GVHD (hazard ratio [HR] = 0.63; P = .032 compared with HP-P2-negative), whereas HP-P3 tended to increase the risk (HR = 1.38; P = .07). Among 381 patients with HP-P1, HP-P1/P3 (HR = 3.35; P = .024) significantly increased the risk of acute GVHD compared with homozygous HP-P1. This study is the first to demonstrate that a genetic difference derived from HLA haplotype itself is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation.

Original languageEnglish
Pages (from-to)4664-4670
Number of pages7
JournalBlood
Volume115
Issue number23
DOIs
Publication statusPublished - Jun 10 2010

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Graft vs Host Disease
HLA Antigens
Grafts
Haplotypes
Hazards
Hematopoietic Stem Cell Transplantation
Stem cells
Transplantation (surgical)
Unrelated Donors
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Alleles
Odds Ratio
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Morishima, S., Ogawa, S., Matsubara, A., Kawase, T., Nannya, Y., Kashiwase, K., ... Morishima, Y. (2010). Impact of highly conserved HLA haplotype on acute graft-versus-host disease. Blood, 115(23), 4664-4670. https://doi.org/10.1182/blood-2009-10-251157

Impact of highly conserved HLA haplotype on acute graft-versus-host disease. / Morishima, Satoko; Ogawa, Seishi; Matsubara, Aiko; Kawase, Takakazu; Nannya, Yasuhito; Kashiwase, Koichi; Satake, Masahiro; Saji, Hiroo; Inoko, Hidetoshi; Kato, Shunichi; Kodera, Yoshihisa; Sasazuki, Takehiko; Morishima, Yasuo.

In: Blood, Vol. 115, No. 23, 10.06.2010, p. 4664-4670.

Research output: Contribution to journalArticle

Morishima, S, Ogawa, S, Matsubara, A, Kawase, T, Nannya, Y, Kashiwase, K, Satake, M, Saji, H, Inoko, H, Kato, S, Kodera, Y, Sasazuki, T & Morishima, Y 2010, 'Impact of highly conserved HLA haplotype on acute graft-versus-host disease', Blood, vol. 115, no. 23, pp. 4664-4670. https://doi.org/10.1182/blood-2009-10-251157
Morishima S, Ogawa S, Matsubara A, Kawase T, Nannya Y, Kashiwase K et al. Impact of highly conserved HLA haplotype on acute graft-versus-host disease. Blood. 2010 Jun 10;115(23):4664-4670. https://doi.org/10.1182/blood-2009-10-251157
Morishima, Satoko ; Ogawa, Seishi ; Matsubara, Aiko ; Kawase, Takakazu ; Nannya, Yasuhito ; Kashiwase, Koichi ; Satake, Masahiro ; Saji, Hiroo ; Inoko, Hidetoshi ; Kato, Shunichi ; Kodera, Yoshihisa ; Sasazuki, Takehiko ; Morishima, Yasuo. / Impact of highly conserved HLA haplotype on acute graft-versus-host disease. In: Blood. 2010 ; Vol. 115, No. 23. pp. 4664-4670.
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