Academic Journal

Dysregulated peripheral proteome reveals NASH-specific signatures identifying patient subgroups with distinct liver biology

التفاصيل البيبلوغرافية
العنوان: Dysregulated peripheral proteome reveals NASH-specific signatures identifying patient subgroups with distinct liver biology
المؤلفون: Natalie Stiglund, Hannes Hagström, Per Stål, Martin Cornillet, Niklas K. Björkström
المصدر: Frontiers in Immunology, Vol 14 (2023)
بيانات النشر: Frontiers Media S.A., 2023.
سنة النشر: 2023
المجموعة: LCC:Immunologic diseases. Allergy
مصطلحات موضوعية: NAFLD, MAFLD, NASH, serum proteome, biomarker, cytokine signaling, Immunologic diseases. Allergy, RC581-607
الوصف: Background and aimsNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The prognosis may vary from simple steatosis to more severe outcomes such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. The understanding of the biological processes leading to NASH is limited and non-invasive diagnostic tools are lacking.MethodsThe peripheral immunoproteome in biopsy-proven NAFL (n=35) and NASH patients (n=35) compared to matched, normal-weight healthy controls (n=15) was studied using a proximity extension assay, combined with spatial and single cell hepatic transcriptome analysis.ResultsWe identified 13 inflammatory serum proteins that, independent of comorbidities and fibrosis stage, distinguished NASH from NAFL. Analysis of co-expression patterns and biological networks further revealed NASH-specific biological perturbations indicative of temporal dysregulation of IL-4/-13, -10, -18, and non-canonical NF-kβ signaling. Of the identified inflammatory serum proteins, IL-18 and EN-RAGE as well as ST1A1 mapped to hepatic macrophages and periportal hepatocytes, respectively, at the single cell level. The signature of inflammatory serum proteins further permitted identification of biologically distinct subgroups of NASH patients.ConclusionNASH patients have a distinct inflammatory serum protein signature, which can be mapped to the liver parenchyma, disease pathogenesis, and identifies subgroups of NASH patients with altered liver biology.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-3224
Relation: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1186097/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2023.1186097
URL الوصول: https://doaj.org/article/16a52c2c1efd4aefb802ca99e201fe8a
رقم الانضمام: edsdoj.16a52c2c1efd4aefb802ca99e201fe8a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16643224
DOI:10.3389/fimmu.2023.1186097