Recipient HLA-C Haplotypes and microRNA 148a/b Binding Sites Have No Impact on Allogeneic Hematopoietic Cell Transplantation Outcomes

Gretchen A. Hoff, Johannes C. Fischer, Katharine Hsu, Sarah Cooley, Jeffrey S. Miller, Tao Wang, Michael Haagenson, Stephen Spellman, Stephanie J. Lee, Markus Uhrberg, Jeffrey M. Venstrom, Michael R. Verneris

Research output: Contribution to journalArticlepeer-review

8 Scopus 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.

Original languageEnglish (US)
Pages (from-to)153-160
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2017

Bibliographical note

Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation

Keywords

  • Allogeneic transplant
  • HLA-C
  • KIR
  • NK cells
  • miRNA

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