PMID- 36219480
OWN - NLM
STAT- MEDLINE
DCOM- 20221214
LR  - 20230422
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 7
IP  - 22
DP  - 2022 Nov 22
TI  - Pathogenicity and impact of HLA class I alleles in aplastic anemia patients of 
      different ethnicities.
LID - 10.1172/jci.insight.163040 [doi]
LID - e163040
AB  - Acquired aplastic anemia (AA) is caused by autoreactive T cell-mediated 
      destruction of early hematopoietic cells. Somatic loss of human leukocyte antigen 
      (HLA) class I alleles was identified as a mechanism of immune escape in surviving 
      hematopoietic cells of some patients with AA. However, pathogenicity, structural 
      characteristics, and clinical impact of specific HLA alleles in AA remain poorly 
      understood. Here, we evaluated somatic HLA loss in 505 patients with AA from 2 
      multi-institutional cohorts. Using a combination of HLA mutation frequencies, 
      peptide-binding structures, and association with AA in an independent cohort of 
      6,323 patients from the National Marrow Donor Program, we identified 19 AA risk 
      alleles and 12 non-risk alleles and established a potentially novel AA HLA 
      pathogenicity stratification. Our results define pathogenicity for the majority 
      of common HLA-A/B alleles across diverse populations. Our study demonstrates that 
      HLA alleles confer different risks of developing AA, but once AA develops, 
      specific alleles are not associated with response to immunosuppression or 
      transplant outcomes. However, higher pathogenicity alleles, particularly 
      HLA-B*14:02, are associated with higher rates of clonal evolution in adult 
      patients with AA. Our study provides insights into the immune pathogenesis of AA, 
      opening the door to future autoantigen identification and improved understanding 
      of clonal evolution in AA.
FAU - Olson, Timothy S
AU  - Olson TS
AD  - Comprehensive Bone Marrow Failure Center and.
AD  - Division of Oncology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Frost, Benjamin F
AU  - Frost BF
AD  - Division of Oncology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
AD  - Division of Hematology/Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Duke, Jamie L
AU  - Duke JL
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Dribus, Marian
AU  - Dribus M
AD  - Department of Pathology and Laboratory Medicine, Tulane University School of 
      Medicine, New Orleans, Louisiana, USA.
FAU - Xie, Hongbo M
AU  - Xie HM
AD  - Department of Biomedical and Health Informatics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Prudowsky, Zachary D
AU  - Prudowsky ZD
AD  - Department of Pediatrics, Division of Hematology/Oncology, Baylor College of 
      Medicine, Houston, Texas, USA.
AD  - Texas Children's Cancer and Hematology Center, Houston, Texas, USA.
FAU - Furutani, Elissa
AU  - Furutani E
AD  - Dana Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical 
      School, Boston, Massachusetts, USA.
FAU - Gudera, Jonas
AU  - Gudera J
AD  - Dana Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical 
      School, Boston, Massachusetts, USA.
AD  - Department of Pediatrics, Dr. von Hauner Children's Hospital, LMU Klinikum 
      Munich, Munich, Germany.
FAU - Shah, Yash B
AU  - Shah YB
AD  - Comprehensive Bone Marrow Failure Center and.
AD  - Division of Oncology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
AD  - Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, 
      Pennsylvania, USA.
FAU - Ferriola, Deborah
AU  - Ferriola D
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Dinou, Amalia
AU  - Dinou A
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Pagkrati, Ioanna
AU  - Pagkrati I
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Kim, Soyoung
AU  - Kim S
AD  - Center for International Blood and Marrow Transplant Research and.
AD  - Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, 
      USA.
FAU - Xu, Yixi
AU  - Xu Y
AD  - Center for International Blood and Marrow Transplant Research and.
FAU - He, Meilun
AU  - He M
AD  - Center for International Blood and Marrow Transplant Research, National Marrow 
      Donor Program/Be The Match, Minneapolis, Minneapolis, USA.
FAU - Zheng, Shannon
AU  - Zheng S
AD  - Division of Hematology/Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Nijim, Sally
AU  - Nijim S
AD  - Division of Hematology/Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Lin, Ping
AU  - Lin P
AD  - Division of Hematology/Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Xu, Chong
AU  - Xu C
AD  - Department of Pathology and Laboratory Medicine, Hospital of the University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
AD  - Parker Institute for Cancer Immunotherapy and Center for Cellular 
      Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Nakano, Taizo A
AU  - Nakano TA
AD  - Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, 
      Colorado, USA.
FAU - Oved, Joseph H
AU  - Oved JH
AD  - Comprehensive Bone Marrow Failure Center and.
AD  - Department of Pediatric Transplant and Cell Therapy, Memorial Sloan Kettering 
      Cancer Center, New York, New York, USA.
FAU - Carreno, Beatriz M
AU  - Carreno BM
AD  - Department of Pathology and Laboratory Medicine, Hospital of the University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
AD  - Parker Institute for Cancer Immunotherapy and Center for Cellular 
      Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Bolon, Yung-Tsi
AU  - Bolon YT
AD  - Center for International Blood and Marrow Transplant Research, National Marrow 
      Donor Program/Be The Match, Minneapolis, Minneapolis, USA.
FAU - Gadalla, Shahinaz M
AU  - Gadalla SM
AD  - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National 
      Cancer Institute, NIH, Rockville, Maryland, USA.
FAU - Marsh, Steven Ge
AU  - Marsh SG
AD  - Anthony Nolan Research Institute and University College London Cancer Institute, 
      Royal Free Campus, London, United Kingdom.
FAU - Paczesny, Sophie
AU  - Paczesny S
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, South Carolina, USA.
FAU - Lee, Stephanie J
AU  - Lee SJ
AD  - Center for International Blood and Marrow Transplant Research and.
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
FAU - Monos, Dimitrios S
AU  - Monos DS
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Shimamura, Akiko
AU  - Shimamura A
AD  - Dana Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical 
      School, Boston, Massachusetts, USA.
FAU - Bertuch, Alison A
AU  - Bertuch AA
AD  - Department of Pediatrics, Division of Hematology/Oncology, Baylor College of 
      Medicine, Houston, Texas, USA.
AD  - Texas Children's Cancer and Hematology Center, Houston, Texas, USA.
FAU - Gragert, Loren
AU  - Gragert L
AD  - Department of Pathology and Laboratory Medicine, Tulane University School of 
      Medicine, New Orleans, Louisiana, USA.
FAU - Spellman, Stephen R
AU  - Spellman SR
AD  - Center for International Blood and Marrow Transplant Research, National Marrow 
      Donor Program/Be The Match, Minneapolis, Minneapolis, USA.
FAU - Babushok, Daria V
AU  - Babushok DV
AD  - Comprehensive Bone Marrow Failure Center and.
AD  - Division of Hematology/Oncology, Department of Medicine, University of 
      Pennsylvania, Philadelphia, Pennsylvania, USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R03 HL160678/HL/NHLBI NIH HHS/United States
GR  - K08 HL132101/HL/NHLBI NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20221122
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Anemia, Aplastic/genetics/pathology
MH  - Alleles
MH  - Histocompatibility Antigens Class I/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA Antigens/genetics
PMC - PMC9746824
OTO - NOTNLM
OT  - Autoimmune diseases
OT  - Autoimmunity
OT  - Clonal selection
OT  - Hematology
OT  - Hematopoietic stem cells
EDAT- 2022/10/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/11/22
CRDT- 2022/10/11 12:03
PHST- 2022/06/27 00:00 [received]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/10/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/10/11 12:03 [entrez]
PHST- 2022/11/22 00:00 [pmc-release]
AID - 163040 [pii]
AID - 10.1172/jci.insight.163040 [doi]
PST - epublish
SO  - JCI Insight. 2022 Nov 22;7(22):e163040. doi: 10.1172/jci.insight.163040.