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

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.

• Authors: Effie W Petersdorf, Theodore A Gooley, Mari Malkki, Andrea P Bacigalupo, Anne Cesbron, Ernette Du Toit, Gerhard Ehninger, Torstein Egeland, Gottfried F Fischer, Thibaut Gervais, Michael D Haagenson, Mary M Horowitz, Katharine Hsu, Pavel Jindra, Alejandro Madrigal, Machteld Oudshoorn, Olle Ringdén, Marlis L Schroeder, Stephen R Spellman, Jean-Marie Tiercy, Andrea Velardi, Campbell S Witt, Colm O'Huigin, Richard Apps, Mary Carrington, International Histocompatibility Working Group in Hematopoietic Cell Transplantation
• Journal: Blood (Blood) Vol. 124 Issue 26 Pg. 3996-4003 (Dec 18 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 25323824 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• HLA-C Antigens

Topics

• 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