Faculty Collaboration Database

Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes. Biol Blood Marrow Transplant 2017 Jan;23(1):153-160

Date

10/18/2016

Pubmed ID

27746218

Pubmed Central ID

PMC5198579

DOI

10.1016/j.bbmt.2016.09.028

Scopus ID

2-s2.0-85006371528 (requires institutional sign-in at Scopus site)   12 Citations

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.

Author List

Hoff GA, Fischer JC, Hsu K, Cooley S, Miller JS, Wang T, Haagenson M, Spellman S, Lee SJ, Uhrberg M, Venstrom JM, Verneris MR

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

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

Adolescent
Adult
Aged
Binding Sites
Child
Child, Preschool
Female
HLA-C Antigens
Haplotypes
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Killer Cells, Natural
Male
MicroRNAs
Middle Aged
Polymorphism, Genetic
Transplantation, Homologous
Treatment Outcome
Young Adult