title: Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes.
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.
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Hoff
authors.affiliation: Institute of Transplantation Diagnostics and Cell Therapeutics, Universitatklinikum Dusseldorf Klinik fur Kinder, Düsseldorf, Germany.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Fischer
authors.affiliation: Blood and Marrow Transplantation, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Katharine
authors.initials: K
authors.lastname: Hsu
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.affiliation: Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.affiliation: Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Blood and Marrow Transplantation, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Institute of Transplantation Diagnostics and Cell Therapeutics, University Clinic of Düsseldorf, Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Uhrberg
authors.affiliation: Blood and Marrow Transplant, University of California San Francisco Medical Center, San Francisco, California.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Venstrom
authors.affiliation: University of Colorado, Pediatric BMT and Cell Therapy, Aurora, Colorado. Electronic address: michael.verneris@UCDevnver.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001665:Binding Sites / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; C550570:MIRN148 microRNA, human; D035683:MicroRNAs
keywords: Allogeneic transplant; HLA-C; KIR; NK cells; miRNA