High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism

Takakazu Kawase, Yasuo Morishima, Keitaro Matsuo, Koichi Kashiwase, Hidetoshi Inoko, Hiroh Saji, Shunichi Kato, Takeo Juji, Yoshihisa Kodera, Takehiko Sasazuki

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combination is little known, and its molecular mechanism to induce acute graft-versus-host disease (aGVHD) remains to be elucidated. A total of 5210 donor-patient pairs who underwent transplantation through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of the HLA allele mismatch combinations and amino acid substitution positions in 6 HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations (high-risk mismatch) for severe aGVHD were identified, and the number of high-risk mismatches was highly associated with the occurrence of severe aGVHD regardless of the presence of mismatch combinations other than high-risk mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class I were identified as those responsible for severe aGVHD. These findings provide evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule. Furthermore, the identification of high-risk mismatch, that is, nonpermissive mismatch, would be beneficial for the selection of a suitable donor.

Original languageEnglish
Pages (from-to)2235-2241
Number of pages7
JournalBlood
Volume110
Issue number7
DOIs
Publication statusPublished - Oct 1 2007

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Graft vs Host Disease
Grafts
Alleles
Tissue Donors
Amino Acid Substitution
Substitution reactions
Amino Acids
HLA-DRB1 Chains
HLA-A Antigens
HLA-B Antigens
Hematopoietic Stem Cell Transplantation
Stem cells
Japan
Transplantation
Bone Marrow
Molecules

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism. / Kawase, Takakazu; Morishima, Yasuo; Matsuo, Keitaro; Kashiwase, Koichi; Inoko, Hidetoshi; Saji, Hiroh; Kato, Shunichi; Juji, Takeo; Kodera, Yoshihisa; Sasazuki, Takehiko.

In: Blood, Vol. 110, No. 7, 01.10.2007, p. 2235-2241.

Research output: Contribution to journalArticle

Kawase, T, Morishima, Y, Matsuo, K, Kashiwase, K, Inoko, H, Saji, H, Kato, S, Juji, T, Kodera, Y & Sasazuki, T 2007, 'High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism', Blood, vol. 110, no. 7, pp. 2235-2241. https://doi.org/10.1182/blood-2007-02-072405
Kawase, Takakazu ; Morishima, Yasuo ; Matsuo, Keitaro ; Kashiwase, Koichi ; Inoko, Hidetoshi ; Saji, Hiroh ; Kato, Shunichi ; Juji, Takeo ; Kodera, Yoshihisa ; Sasazuki, Takehiko. / High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism. In: Blood. 2007 ; Vol. 110, No. 7. pp. 2235-2241.
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