PMID- 33971035
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20221207
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 74
IP  - 4
DP  - 2021 Oct
TI  - Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in 
      Children of European Ancestry.
PG  - 2032-2046
LID - 10.1002/hep.31893 [doi]
AB  - BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in 
      adults is associated with possession of human leukocyte antigen (HLA) class I 
      (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on 
      geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, 
      AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically 
      different from their adult counterparts. We aimed to define the relationship 
      between HLA profile and disease course, severity, and outcome in juvenile AILD. 
      APPROACH AND RESULTS: We studied 236 children of European ancestry (152 female 
      [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with 
      AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 
      14.5 years). Class I and II HLA genotyping was performed using 
      PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype 
      impart predisposition to all three forms of AILD. Homozygosity 
      for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which 
      independently confers susceptibility to AIH in adults, was infrequent in AIH-1 
      and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all 
      forms of AILD. Distinct HLA class II alleles predispose to the different 
      subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to 
      AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis 
      at disease onset, and possession of these two genes in addition to DRB1*07 is 
      associated with a more severe disease in all three subgroups. CONCLUSIONS: Unique 
      HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be 
      useful in predicting responsiveness to immunosuppressive treatment and course.
CI  - (c) 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of 
      American Association for the Study of Liver Diseases.
FAU - Ma, Yun
AU  - Ma Y
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Su, Haibin
AU  - Su H
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Department of Liver Disease of Chinese PLA General Hospital, The Fifth Medical 
      Center of Chinese PLA General Hospital, Beijing, China.
FAU - Yuksel, Muhammed
AU  - Yuksel M
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Koc University Research Centre for Translational Medicine, Istanbul, Turkey.
FAU - Longhi, Maria Serena
AU  - Longhi MS
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical 
      School, Boston, MA, USA.
FAU - McPhail, Mark J
AU  - McPhail MJ
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Wang, Pengyun
AU  - Wang P
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Bansal, Sanjay
AU  - Bansal S
AD  - Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, 
      United Kingdom.
FAU - Wong, Guan-Wee
AU  - Wong GW
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Department of Medicine, Ng Teng Fong General Hospital, Singapore.
FAU - Graham, Jonathon
AU  - Graham J
AUID- ORCID: 0000-0003-1637-7024
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Yang, Li
AU  - Yang L
AUID- ORCID: 0000-0003-3821-9342
AD  - Department of Gastroenterology & Hepatology, West China Hospital, Sichuan 
      University, Chengdu, China.
FAU - J Thompson, Richard
AU  - J Thompson R
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, 
      United Kingdom.
FAU - Doherty, Derek G
AU  - Doherty DG
AD  - Discipline of Immunology, School of Medicine, Trinity College Dublin, Dublin, 
      Ireland.
FAU - Hadzic, Nedim
AU  - Hadzic N
AD  - Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, 
      United Kingdom.
FAU - Zen, Yoh
AU  - Zen Y
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Quaglia, Alberto
AU  - Quaglia A
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Department of Cellular Pathology, Royal Free London NHS Foundation Trust, UCL 
      Cancer Institute, Research Department of Pathology, London, United Kingdom.
FAU - Heneghan, Michael A
AU  - Heneghan MA
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Samyn, Marianne
AU  - Samyn M
AD  - Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, 
      United Kingdom.
FAU - Vergani, Diego
AU  - Vergani D
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
FAU - Mieli-Vergani, Giorgina
AU  - Mieli-Vergani G
AD  - Institute of Liver Studies, MowatLabs, Department of Inflammation Biology, School 
      of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's 
      College London, London, United Kingdom.
AD  - Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, 
      United Kingdom.
LA  - eng
GR  - G0902288/MRC_/Medical Research Council/United Kingdom
GR  - R01 DK108894/DK/NIDDK NIH HHS/United States
GR  - R01 DK124408/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210621
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (HLA-B8 Antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Cholangitis, Sclerosing/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/genetics
MH  - HLA-A1 Antigen/genetics
MH  - HLA-B8 Antigen/genetics
MH  - HLA-DR3 Antigen/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - Hepatitis, Autoimmune/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Severity of Illness Index
MH  - White People/*genetics
PMC - PMC8463472
MID - NIHMS1710701
EDAT- 2021/05/11 06:00
MHDA- 2022/01/11 06:00
PMCR- 2021/11/01
CRDT- 2021/05/10 18:05
PHST- 2021/04/03 00:00 [revised]
PHST- 2020/12/02 00:00 [received]
PHST- 2021/04/28 00:00 [accepted]
PHST- 2021/05/11 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2021/05/10 18:05 [entrez]
PHST- 2021/11/01 00:00 [pmc-release]
AID - 10.1002/hep.31893 [doi]
PST - ppublish
SO  - Hepatology. 2021 Oct;74(4):2032-2046. doi: 10.1002/hep.31893. Epub 2021 Jun 21.