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

Publication Type:

Journal Article

Source:

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (2016)

Abstract:

Natural Killer (NK) cells are important in graft versus leukemia responses following hematopoietic cell transplantation (HCT). A variety of surface receptors dictate NK cell function, including killer immunoglobulin receptor (KIR) 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 one C2 allele, while 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 (i.e., surface density), as predicted by the miR148a/b binding SNP, was also not with associated transplant outcomes. Collectively, neither HLA-C surface expression, as determined by miR148a/b, nor recipient HLA-C epitopes (C1, C2) are associated allo-HCT outcomes.