PMID- 32692457
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20211204
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 73
IP  - 4
DP  - 2021 Apr
TI  - Next-Generation Immunosequencing Reveals Pathological T-Cell Architecture in 
      Autoimmune Hepatitis.
PG  - 1436-1448
LID - 10.1002/hep.31473 [doi]
AB  - BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic liver disease that 
      regularly relapses when immunosuppression is tapered. It is thought to be driven 
      by T-cells, whereas the etiologic impact of an apparently deregulated B lineage 
      system, as evidenced by hypergammaglobulinemia and autoantibodies, remains 
      elusive. We set out to investigate T and B cell repertoires supporting chronic 
      inflammation in AIH. APPROACH AND RESULTS: T and B cell receptor (TCR/BCR) and 
      human leukocyte antigen (HLA) next-generation immunosequencing were used to 
      record immune signatures from a cohort of 60 patients with AIH and disease 
      controls. Blood and liver B lineage immune metrics were not indicative of a 
      dominant directional antigen selection apart from a slight skewing of IGHV-J 
      genes. More importantly, we found strong AIH-specific TRBV-J skewing not 
      attributable to the HLA-DRB1 specificities of the cohort. This TCR repertoire 
      bias was generated as a result of peripheral T cell (de)selection and persisted 
      in disease remission. Using a clustering algorithm according to antigenic 
      specificity, we identified liver TCR clusters that were shared between patients 
      with AIH but were absent or deselected in patients with other liver pathologies. 
      CONCLUSIONS: Patients with AIH show profound and persisting T-cell architectural 
      changes that may explain high relapse rates after tapering immunosuppression. 
      Liver T-cell clusters shared between patients may mediate liver damage and 
      warrant further study.
CI  - (c) 2020 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of 
      American Association for the Study of Liver Diseases.
FAU - Schultheiss, Christoph
AU  - Schultheiss C
AUID- ORCID: 0000-0001-9789-5776
AD  - Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University 
      Halle-Wittenberg, Halle (Saale), Germany.
FAU - Simnica, Donjete
AU  - Simnica D
AD  - Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University 
      Halle-Wittenberg, Halle (Saale), Germany.
FAU - Willscher, Edith
AU  - Willscher E
AD  - Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University 
      Halle-Wittenberg, Halle (Saale), Germany.
FAU - Oberle, Anna
AU  - Oberle A
AD  - Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus 
      Wad Tumorzentrum, University Cancer Center Hamburg, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Fanchi, Lorenzo
AU  - Fanchi L
AD  - ENPICOM B.V., 's-Hertogenbosch, the Netherlands.
FAU - Bonzanni, Nicola
AU  - Bonzanni N
AD  - ENPICOM B.V., 's-Hertogenbosch, the Netherlands.
FAU - Wildner, Nils H
AU  - Wildner NH
AD  - First Department of Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Schulze Zur Wiesch, Julian
AU  - Schulze Zur Wiesch J
AD  - First Department of Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Weiler-Normann, Christina
AU  - Weiler-Normann C
AD  - First Department of Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Lohse, Ansgar W
AU  - Lohse AW
AD  - First Department of Medicine, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Binder, Mascha
AU  - Binder M
AD  - Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University 
      Halle-Wittenberg, Halle (Saale), Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210208
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B-Lymphocytes/immunology
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - HLA-DRB1 Chains/genetics
MH  - *Hepacivirus
MH  - Hepatitis C/blood/*immunology
MH  - Hepatitis, Autoimmune/blood/*immunology/therapy
MH  - High-Throughput Nucleotide Sequencing/*methods
MH  - Humans
MH  - Immunosuppression Therapy/methods
MH  - Liver Cirrhosis, Biliary/blood/*immunology
MH  - Male
MH  - Middle Aged
MH  - Receptors, Antigen, B-Cell/genetics
MH  - Receptors, Antigen, T-Cell/*genetics
MH  - Recurrence
MH  - T-Lymphocytes/*immunology
MH  - Young Adult
EDAT- 2020/07/22 06:00
MHDA- 2021/10/27 06:00
CRDT- 2020/07/22 06:00
PHST- 2020/06/08 00:00 [revised]
PHST- 2020/03/20 00:00 [received]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/07/22 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2020/07/22 06:00 [entrez]
AID - 10.1002/hep.31473 [doi]
PST - ppublish
SO  - Hepatology. 2021 Apr;73(4):1436-1448. doi: 10.1002/hep.31473. Epub 2021 Feb 8.