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Causal effects of immune cell phenotypes on the risk of autoimmune liver diseases: a bidirectional two-sample Mendelian randomization study

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机构: [1]State Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China. [2]The Key Laboratory of Molecular Pathology in Tumors of Guangxi Higher Education Institutions, Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China. [3]Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China. [4]Precision Regenerative Medicine Research Centre, Medical Science Division, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China.
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关键词: Immune phenotype autoimmune liver diseases (AILDs) Mendelian randomization (MR) genomewide association study (GWAS)

摘要:
Currently, the relationship between immune cell phenotypes and susceptibility to autoimmune liver diseases (AILDs) remains underexplored. This study aims to investigate potential causal associations between immune cell phenotypes and AILDs using a bioinformatics approach.We utilized a two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cell phenotypes and susceptibility to AILDs, including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The data of 731 immune cell phenotypes were sourced from a study cohort with 3,757 individuals, while all AILDs summary data were obtained from an open-access database containing the data of AIH, PBC and PSC from 485,234, 24,510 and 14,890 subjects, respectively.For AIH, its incidence was negatively influenced by three phenotypes of natural killer (NK) cells [HLA-DR+ NK absolute count (AC), HLA-DR+ NK %NK, and HLA-DR+ NK %CD3- lymphocyte] and two phenotypes of monocytes (CD14+ CD16+ monocyte AC, CD16 on CD14- CD16+ monocyte), as well as positively affected by HLA-DR on plasmacytoid dendritic cell (DC) and HLA-DR on CD33- HLA-DR+ myeloid cell. For PBC, its susceptibility was positively impacted by three phenotypes of B cells, i.e., CD27 on CD24+ CD27+ B cell, CD27 on IgD+ CD38- unswitched memory (unsw mem) B cell, and CD27 on memory B cell. For PSC, its risk was negatively correlated with CD28 on CD45RA- CD4 not regulatory T (Treg) cell and FSC-A on CD4+ NK cell.This study suggests a potential causal relationship between immune cells and AILDs, providing preliminary insights into their immunological basis and informing the potential therapeutic targets for further functional studies in treating AILDs.Copyright © 2025 AME Publishing Company. All rights reserved.

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大类 | 4 区 医学
小类 | 4 区 胃肠肝病学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 胃肠肝病学
第一作者:
第一作者机构: [1]State Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China. [2]The Key Laboratory of Molecular Pathology in Tumors of Guangxi Higher Education Institutions, Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
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通讯作者:
通讯机构: [1]State Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China. [2]The Key Laboratory of Molecular Pathology in Tumors of Guangxi Higher Education Institutions, Department of Pathology, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
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