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Title: Next-generation immunosequencing reveals pathological T cell architecture in autoimmune hepatitis
Author(s): Schultheiß, Christoph
Simnica, Donjete
Willscher, Edith
Oberle, Anna
Fanchi, Lorenzo
Bonzanni, Nicola
Wildner, Nils H.
Schulze zur Wiesch, Julian Constantin RaimarLook up in the Integrated Authority File of the German National Library
Weiler-Normann, Christina
Lohse, Ansgar W.
Binder, MaschaLook up in the Integrated Authority File of the German National Library
Issue Date: 2021
Type: Article
Language: English
Abstract: 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.
Open Access: Open access publication
License: (CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0(CC BY-NC 4.0) Creative Commons Attribution NonCommercial 4.0
Sponsor/Funder: Publikationsfond MLU
Journal Title: Hepatology
Publisher: Wiley Interscience
Publisher Place: New York [u.a.]
Volume: 73
Issue: 4
Original Publication: 10.1002/hep.31473
Page Start: 1436
Page End: 1448
Appears in Collections:Open Access Publikationen der MLU

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