PMID- 30316972
OWN - NLM
STAT- MEDLINE
DCOM- 20190325
LR  - 20190325
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 79
IP  - 12
DP  - 2018 Dec
TI  - Improved accuracy of clinical HLA genotyping by next-generation DNA sequencing 
      affects unrelated donor search results for hematopoietic stem cell 
      transplantation.
PG  - 848-854
LID - S0198-8859(18)30932-7 [pii]
LID - 10.1016/j.humimm.2018.10.008 [doi]
AB  - Matching of human leukocyte antigen (HLA) genes is critically important in 
      hematopoietic stem cell transplantation (HSCT). HLA genes are highly polymorphic 
      and HLA matching has historically been limited by technologies that are unable to 
      unambiguously determine HLA genotypes. Next generation DNA sequencing (NGS) 
      overcomes these limitations by enabling near full-gene sequences with phase 
      determination for heterozygous alleles. Here we examine the efficacy and utility 
      of HLA-NGS in the clinical setting. In a 54-sample validation study and 955 
      patient samples subsequently tested using HLA-NGS, we observed significant 
      improvement in the ability to unambiguously identify HLA genotypes in both the 
      validation (97.3%) and clinical (97.4%) sample cohorts compared to previous 
      standard-of care HLA genotyping methods. We modeled the clinical impact of this 
      improved diagnostic ability by comparing National Marrow Donor Program (NMDP) 
      search results for 56 patients using HLA-NGS genotypes and simulated 
      standard-of-care HLA genotypes. Surprisingly, we observed significant differences 
      in 7.1% of NMDP searches, with improved unambiguous HLA genotyping correlating 
      with improved prediction of finding well-matched and partially-matched unrelated 
      HSCT donors. These data demonstrate that HLA-NGS can provide highly accurate and 
      unambiguous HLA genotyping that facilitates donor selection for allogeneic HSCT.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Allen, Elizabeth S
AU  - Allen ES
AD  - Department of Pathology, University of California San Diego, La Jolla, CA, USA.
FAU - Yang, Bing
AU  - Yang B
AD  - Department of Pathology, University of California San Diego, La Jolla, CA, USA.
FAU - Garrett, Jodi
AU  - Garrett J
AD  - Division of Bone Marrow Transplantation, University of California San Diego, La 
      Jolla, CA, USA.
FAU - Ball, Edward D
AU  - Ball ED
AD  - Division of Bone Marrow Transplantation, University of California San Diego, La 
      Jolla, CA, USA.
FAU - Maiers, Martin
AU  - Maiers M
AD  - Center for International Blood and Marrow Transplant Research, Milwaukee, WI, 
      USA.
FAU - Morris, Gerald P
AU  - Morris GP
AD  - Department of Pathology, University of California San Diego, La Jolla, CA, USA. 
      Electronic address: gpmorris@ucsd.edu.
LA  - eng
PT  - Journal Article
DEP - 20181011
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Genotype
MH  - Genotyping Techniques/*methods
MH  - HLA Antigens/*genetics
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Histocompatibility Testing/methods
MH  - Humans
MH  - Reproducibility of Results
MH  - Transplantation, Homologous
MH  - *Unrelated Donors
OTO - NOTNLM
OT  - HLA
OT  - Hematopoietic stem cell transplantation
OT  - Next-generation DNA sequencing
EDAT- 2018/10/15 06:00
MHDA- 2019/03/26 06:00
CRDT- 2018/10/15 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/09/10 00:00 [revised]
PHST- 2018/10/10 00:00 [accepted]
PHST- 2018/10/15 06:00 [pubmed]
PHST- 2019/03/26 06:00 [medline]
PHST- 2018/10/15 06:00 [entrez]
AID - S0198-8859(18)30932-7 [pii]
AID - 10.1016/j.humimm.2018.10.008 [doi]
PST - ppublish
SO  - Hum Immunol. 2018 Dec;79(12):848-854. doi: 10.1016/j.humimm.2018.10.008. Epub 
      2018 Oct 11.