Clin Immunol
Department of Medicine, Division of Clinical Immunology, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:
Published: November 2023
Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and non-alcoholic steatohepatitis (NASH) are chronic liver diseases (CLDs) of distinct etiologies that represent a public health risk with limited therapeutic options. A common feature among CLDs is an aggressive T cell response resulting in destruction of liver tissue and fibrosis. Here, we assessed the presence and nature of T cell inflammation in late-stage human AIH, PSC and NASH and examined whether targeting the T cell response can improve disease pathology in a mouse model (Traf6ΔTEC) of spontaneous AIH. T cell infiltration and ensuing inflammatory pathways were present in human AIH and PSC and to a lesser extent in NASH. However, we observed qualitative differences in infiltrating T cell subsets and upregulation of inflammatory pathways among these diseases, while mouse and human AIH exhibited similar immunogenic signatures. While gene expression profiles differed among diseases, we identified 52 genes commonly upregulated across all diseases that included the JAK3 tyrosine kinase. Therapeutic targeting of chronic AIH with the JAK inhibitor tofacitinib reduced hepatic T cell infiltration, AIH histopathology and associated immune parameters in treated Traf6ΔTEC mice. Our results indicate that targeting T cell responses in established hepatic autoimmune inflammation is a feasible strategy for developing novel therapeutic approaches to treat AIH and possibly other CLDs irrespective of etiology.
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http://dx.doi.org/10.1016/j.clim.2023.109807 | DOI Listing |
Cureus
December 2024
Internal Medicine, Tobago Regional Health Authority, Scarborough, TTO.
Autoimmune hepatitis (AIH) is rare, and the diagnosis is not always clear-cut. It is associated with increased morbidity and mortality for the pregnant mother and fetus. Frequent pregnancy testing of women in childbearing years who have a known diagnosis of AIH may be necessary, even after counseling on family planning takes place.
View Article and Find Full Text PDFLiver Int
February 2025
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background And Aim: Discriminating between idiosyncratic drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) is critical yet challenging. We aim to develop and validate a machine learning (ML)-based model to aid in this differentiation.
Methods: This multicenter cohort study utilised a development set from Beijing Friendship Hospital, with retrospective and prospective validation sets from 10 tertiary hospitals across various regions of China spanning January 2009 to May 2023.
J Clin Invest
January 2025
Institute for Research in Biomedicine (IRB), Bellinzona, Switzerland.
Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones.
View Article and Find Full Text PDFJ Clin Invest
January 2025
How are autoreactive T cells induced and regulated in patients with autoimmune disease? This question lies at the core of understanding autoimmune disease pathologies, yet it has remained elusive due to host variability and the complexity of the immune system. In this issue of the JCI, Kramer and colleagues used autoimmune hepatitis (AIH) as a model to explore the maintenance of autoreactive CD4+ T cells specific to O-phosphoseryl-tRNA:selenocysteine tRNA synthase (SepSecS). The findings provide insight into the interaction between T cells and B cells in AIH pathogenesis that may reflect a shared mechanism among other autoimmune diseases.
View Article and Find Full Text PDFSaudi Med J
January 2025
From the Department of Surgery (Aljiffry, Dahal, Baeisa, Alzahrani, Saleem, Alshahrany), from the Department of Medicine (Hijji, Alsahafi, Alghamdi, Mosli), from the Faculty of Medicine (Aljiffry, Daha, Baeisa, Alzahrani, Alshahrany, Hijji, Alsahafi, Saleem, Alghamdi, Mosli), King Abdulaziz University, from the Inflammatory Bowel Disease Research Group (Alsahafi, Mosli), and from the Gastrointestinal Oncology Unit (Saleem, Alghamdi), King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia.
Objectives: To evaluate the features and frequency of hepatobiliary diseases in individuals with Inflammatory bowel disease (IBD).
Methods: This retrospective study included all IBD patients at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The primary focus was on the prevalence of hepatobiliary diseases, such as primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH), and others.
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