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

Petersdorf, Effie W
Gooley, Theodore A
Malkki, Mari
Bacigalupo, Andrea P
Cesbron, Anne
Du Toit, Ernette
Ehninger, Gerhard
Egeland, Torstein
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Published in Blood. 2014, vol. 124, no. 26, p. 3996-4003
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 AdolescentAdultAgedAllelesFemaleGraft vs Host DiseaseHLA-C Antigens/metabolismHematopoietic Stem Cell TransplantationHistocompatibility/immunologyHumansLeukemia/immunology/therapyMaleMiddle AgedMultivariate AnalysisMyelodysplastic Syndromes/immunology/therapyRetrospective StudiesTreatment OutcomeUnrelated DonorsYoung Adult
PMID: 25323824
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Research group Compatibilité tissulaire et transplantation clinique (562)
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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 https://archive-ouverte.unige.ch/unige:78607

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Deposited on : 2015-12-14

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