Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation

Satoko Morishima, Takashi Shiina, Shingo Suzuki, Seishi Ogawa, Aiko Sato-Otsubo, Koichi Kashiwase, Fumihiro Azuma, Toshio Yabe, Masahiro Satake, Shunichi Kato, Yoshihisa Kodera, Takehiko Sasazuki, Yasuo Morishima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

HLA-DPB1 T-cell epitope (TCE) mismatching algorithm and rs9277534 SNP at the 39 untranslated region (39UTR) in the HLA-DPB1 gene are key factors for transplant-related events in unrelated hematopoietic cell transplantation (UR-HCT). However, the association of these 2 mechanisms has not been elucidated. We analyzed 19 frequent HLA-DPB1 alleles derived from Japanese healthy subjects by next-generation sequencing of the entire HLA-DPB1 gene region and multi-SNP data of the HLA region in 1589 UR-HCT pairs. The risk of acute graft-versus-host disease (aGVHD) was analyzed in 1286 patients with single HLA-DPB1 mismatch UR-HCT. The phylogenetic tree constructed using the entire gene region demonstrated that HLA-DPB1 alleles were divided into 2 groups, HLA-DP2 and HLA-DP5. Although a phylogenetic relationship in the genomic region from exon 3 to 39UTR (Ex3-39UTR) obviously supported the division of HLA-DP2 and HLA-DP5 groups, which in exon 2 showed intermingling of HLA-DPB1 alleles in a non–HLA-DP2 and non–HLA-DP5-group manner. Multi-SNP data also showed 2 discriminative HLA-DPB1 groups according to Ex3-39UTR. Risk of grade 2-4 aGVHD was significantly higher in patient HLA-DP5 group mismatch than patient HLA-DP2 group mismatch (hazard ratio, 1.28; P 5 .005), regardless of donor mismatch HLA-DP group. Regarding TCE mismatch, increasing risk of aGVHD in patient HLA-DP5 group mismatch and TCE-nonpermissive mismatch were observed only in patients with TCE-permissive mismatch and patient HLA-DP2 group mismatch, respectively. Evolutionary analysis revealed that rs9277534 represented a highly conserved HLA-DPB1 Ex3-39UTR region and may provoke aGVHD differently to TCE mismatching algorithm, reflecting exon 2 polymorphisms. These findings enrich our understanding of the mechanism of aGVHD in HLA-DPB1 mismatch UR-HCT.

Original languageEnglish
Article numberY
Pages (from-to)808-817
Number of pages10
JournalBlood
Volume131
Issue number7
DOIs
Publication statusPublished - Feb 15 2018

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Unrelated Donors
Stem Cell Transplantation
Stem cells
Alleles
T-Lymphocyte Epitopes
Graft vs Host Disease
Grafts
Cell Transplantation
Exons
Transplantation (surgical)
Untranslated Regions
Single Nucleotide Polymorphism
Genes
HLA-DP Antigens
HLA-DPB1 antigen
Transplants
Polymorphism
Hazards
Healthy Volunteers
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Morishima, S., Shiina, T., Suzuki, S., Ogawa, S., Sato-Otsubo, A., Kashiwase, K., ... Morishima, Y. (2018). Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. Blood, 131(7), 808-817. [Y]. https://doi.org/10.1182/blood-2017-08-801449

Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. / Morishima, Satoko; Shiina, Takashi; Suzuki, Shingo; Ogawa, Seishi; Sato-Otsubo, Aiko; Kashiwase, Koichi; Azuma, Fumihiro; Yabe, Toshio; Satake, Masahiro; Kato, Shunichi; Kodera, Yoshihisa; Sasazuki, Takehiko; Morishima, Yasuo.

In: Blood, Vol. 131, No. 7, Y, 15.02.2018, p. 808-817.

Research output: Contribution to journalArticle

Morishima, S, Shiina, T, Suzuki, S, Ogawa, S, Sato-Otsubo, A, Kashiwase, K, Azuma, F, Yabe, T, Satake, M, Kato, S, Kodera, Y, Sasazuki, T & Morishima, Y 2018, 'Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation', Blood, vol. 131, no. 7, Y, pp. 808-817. https://doi.org/10.1182/blood-2017-08-801449
Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K et al. Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. Blood. 2018 Feb 15;131(7):808-817. Y. https://doi.org/10.1182/blood-2017-08-801449
Morishima, Satoko ; Shiina, Takashi ; Suzuki, Shingo ; Ogawa, Seishi ; Sato-Otsubo, Aiko ; Kashiwase, Koichi ; Azuma, Fumihiro ; Yabe, Toshio ; Satake, Masahiro ; Kato, Shunichi ; Kodera, Yoshihisa ; Sasazuki, Takehiko ; Morishima, Yasuo. / Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. In: Blood. 2018 ; Vol. 131, No. 7. pp. 808-817.
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