Faculty Collaboration Database

Analysis of Single Nucleotide Polymorphisms in the Gamma Block of the Major Histocompatibility Complex in Association with Clinical Outcomes of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study. Biol Blood Marrow Transplant 2019 Apr;25(4):664-672

Date

12/12/2018

Pubmed ID

30537553

Pubmed Central ID

PMC6453713

DOI

10.1016/j.bbmt.2018.12.008

Scopus ID

2-s2.0-85059527914 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

HLA haplotype mismatches have been associated with an elevated risk of acute graft-versus-host disease (aGVHD) in patients undergoing HLA-matched unrelated donor (URD) hematopoietic cell transplantation (HCT). The gamma block (GB) is located in the central MHC region between beta and delta blocks (encoding HLA-B and -C and HLA-DQ and -DR antigens, respectively) and contains numerous inflammatory and immune regulatory genes, including Bf, C2, and C4 genes. A single-center study showed that mismatches in SNPs c.2918+98G, c.3316C, and c.4385C in the GB block (C4 SNPs) were associated with higher risk of grade III-IV aGVHD. We investigated the association of GB SNP (GBS) mismatches with outcomes after 10/10 and 9/10 URD HCT (n = 714). The primary outcome was acute GVHD. Overall survival, disease-free survival, transplantation-related mortality, relapse, chronic GVHD, and engraftment were also analyzed. DNA samples were GBS genotyped by identifying 338 SNPs across 20 kb using the Illumina NGS platform. The overall 100-day incidence of aGVHD grade II-IV and II-IV were 41% and 17%, respectively. The overall incidence of matching at all GBSs tested and at the C4 SNPs were 23% and 81%, respectively. Neither being matched across all GB SNPs tested (versus mismatched) nor having a higher number of GBS mismatches was associated with transplantation outcomes. There was no association between C4 SNP mismatches and outcomes except for an unexpected significant association between having 2 C4 SNP mismatches and a higher hazard ratio (HR) for relapse (association seen in 15 patients only; HR, 3.38, 95% confidence interval, 1.75 to 6.53; P = .0003). These data do not support the hypothesis that mismatching at GB is associated with outcomes after HCT.

Author List

Askar M, Sayer D, Wang T, Haagenson M, Spellman SR, Lee SJ, Madbouly A, Fleischhauer K, Hsu KC, Verneris MR, Thomas D, Zhang A, Sobecks RM, Majhail NS, Center for International Blood and Marrow Transplant Research Immunology Working Committee

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

Female
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Major Histocompatibility Complex
Male
Middle Aged
Polymorphism, Single Nucleotide
Transplantation Conditioning
Treatment Outcome