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; Fischer, Gottfried F; Gervais, Thibaut; Haagenson, Michael D; Horowitz, Mary M; Hsu, Katharine; Jindra, Pavel; Madrigal, Alejandro; Oudshoorn, Machteld; Ringdén, Olle; Schroeder, Marlis L; Spellman, Stephen R; Tiercy, Jean-Marie; Velardi, Andrea; Witt, Campbell S; O'Huigin, Colm; Apps, Richard; Carrington, Mary

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Title		HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation
Authors		Petersdorf, Effie W Gooley, Theodore A Malkki, Mari Bacigalupo, Andrea P Cesbron, Anne Du Toit, Ernette Ehninger, Gerhard Egeland, Torstein Fischer, Gottfried F Gervais, Thibaut Haagenson, Michael D Horowitz, Mary M Hsu, Katharine Jindra, Pavel Madrigal, Alejandro Oudshoorn, Machteld Ringdén, Olle Schroeder, Marlis L Spellman, Stephen R Tiercy, Jean-Marie Velardi, Andrea Witt, Campbell S O'Huigin, Colm Apps, Richard Carrington, Mary show all authors [1 - 25]
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		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
Identifiers		DOI: 10.1182/blood-2014-09-599969 PMID: 25323824
Full text		Article (Published version) (675 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Research group		Compatibilité tissulaire et transplantation clinique (562)
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. https://archive-ouverte.unige.ch/unige:78607