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HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood 2014 Dec 18;124(26):3996-4003 PMID: 25323824 PMCID: PMC4271183

Pubmed ID

25323824

DOI

10.1182/blood-2014-09-599969

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.

Author List

Petersdorf EW, Gooley TA, Malkki M, Bacigalupo AP, Cesbron A, Du Toit E, Ehninger G, Egeland T, Fischer GF, Gervais T, Haagenson MD, Horowitz MM, Hsu K, Jindra P, Madrigal A, Oudshoorn M, Ringdén O, Schroeder ML, Spellman SR, Tiercy JM, Velardi A, Witt CS, O'Huigin C, Apps R, Carrington M, International Histocompatibility Working Group in Hematopoietic Cell Transplantation

Author

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84919465848   58 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Alleles
Female
Graft vs Host Disease
HLA-C Antigens
Hematopoietic Stem Cell Transplantation
Histocompatibility
Humans
Leukemia
Male
Middle Aged
Multivariate Analysis
Myelodysplastic Syndromes
Retrospective Studies
Treatment Outcome
Unrelated Donors
Young Adult
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70