Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes
Year: 2016
Type: article
Study design: Observational Study
Abstract: Natural killer cells are important in graft-versus-leukemia responses after hematopoietic cell transplantation (HCT). A variety of surface receptors dictates natural killer cell function, including killer cell immunoglobulin-like receptor recognition of HLA-C. Previous single-center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic HCT outcomes; specifically, recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least 1 C2 allele, whereas the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes. In this analysis we aimed to validate these findings in a large multicenter study. We also set out to determine whether surface expression of recipient HLA-C, determined by polymorphism in a microRNA (miR-148a/b) binding site within the 3'-region of the HLA-C transcript, was associated with transplant outcomes. In this large registry cohort, we were unable to confirm the prior findings regarding recipient HLA-C epitope status and outcome. Additionally, HLA-C surface expression (ie, surface density), as predicted by the miR-148a/b binding single nucleotide polymorphism, was also not with associated transplant outcomes. Collectively, neither HLA-C surface expression, as determined by miR-148a/b, nor recipient HLA-C epitopes (C1, C2) are associated with allogeneic HCT outcomes.
Institutions: University of Minnesota, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, Memorial Sloan Kettering Cancer Center, Medical College of Wisconsin, National Marrow Donor Program, Fred Hutch Cancer Center, University of California San Francisco Medical Center, University of Colorado Denver
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
Awards: Immunobiology of Allogeneic Hematopoietic Cell Transplantation, Genetic epidemiology of hematopoietic cell transplant outcomes, Lymphoid Tissue Inducer/NK22 Cells and Post-transplant Immune Recovery, Inducing NK cells to remember and fight cancer, Cancer Center Support Grant, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research, Medical Student Summer Research Program in Infection and Immunity, Cancer Center Support Grant, NK cells, their receptors and cancer therapy, Off-the-Shelf Immune Effector Cells for Hematological Malignancies
OpenAlex ID: W2531680868