Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.

Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate u...

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Main Authors: Michele May-Sien Tana, Arielle Klepper, Amy Lyden, Angela Oliveira Pisco, Maira Phelps, Breann McGee, Kelsey Green, Sandy Feng, Joseph DeRisi, Emily Dawn Crawford, Craig S Lammert
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264307&type=printable
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author Michele May-Sien Tana
Arielle Klepper
Amy Lyden
Angela Oliveira Pisco
Maira Phelps
Breann McGee
Kelsey Green
Sandy Feng
Joseph DeRisi
Emily Dawn Crawford
Craig S Lammert
author_facet Michele May-Sien Tana
Arielle Klepper
Amy Lyden
Angela Oliveira Pisco
Maira Phelps
Breann McGee
Kelsey Green
Sandy Feng
Joseph DeRisi
Emily Dawn Crawford
Craig S Lammert
author_sort Michele May-Sien Tana
collection DOAJ
description Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.
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language English
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publisher Public Library of Science (PLoS)
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spelling doaj-art-b3e90cb41e634ac896060b18bbbe5c0d2025-08-20T02:46:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01173e026430710.1371/journal.pone.0264307Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.Michele May-Sien TanaArielle KlepperAmy LydenAngela Oliveira PiscoMaira PhelpsBreann McGeeKelsey GreenSandy FengJoseph DeRisiEmily Dawn CrawfordCraig S LammertAutoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264307&type=printable
spellingShingle Michele May-Sien Tana
Arielle Klepper
Amy Lyden
Angela Oliveira Pisco
Maira Phelps
Breann McGee
Kelsey Green
Sandy Feng
Joseph DeRisi
Emily Dawn Crawford
Craig S Lammert
Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
PLoS ONE
title Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
title_full Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
title_fullStr Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
title_full_unstemmed Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
title_short Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.
title_sort transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0264307&type=printable
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