en
Scientific article
English

HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation

Published inBlood, vol. 124, no. 26, p. 3996-4003
Publication date2014
Abstract

Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease.

Keywords
  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Female
  • Graft vs Host Disease
  • HLA-C Antigens/metabolism
  • Hematopoietic Stem Cell Transplantation
  • Histocompatibility/immunology
  • Humans
  • Leukemia/immunology/therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myelodysplastic Syndromes/immunology/therapy
  • Retrospective Studies
  • Treatment Outcome
  • Unrelated Donors
  • Young Adult
Citation (ISO format)
PETERSDORF, Effie W et al. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. In: Blood, 2014, vol. 124, n° 26, p. 3996–4003. doi: 10.1182/blood-2014-09-599969
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ISSN of the journal0006-4971
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