ArticleHepatology (Baltimore, Md.)2014
Ongoing activation of autoantigen-specific B cells in primary biliary cirrhosis.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 96 citations in OpenAlex.
- Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2015Trial
- Immune cell remodelling and the peribiliary immune niche in primary biliary cholangitis: from initiation to chronicity.eGastroenterology · 2026Review
- Review
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- Regulatory T cells-related gene in primary sclerosing cholangitis: evidence from Mendelian randomization and transcriptome data.Genes and immunity · 2024Article
- Antibodies directed against bacterial antigens in sera of Polish patients with primary biliary cholangitis.Frontiers in cellular and infection microbiology · 2024Article
- Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.BMC cancer · 2023Article
- Inflammasome and pyroptosis in autoimmune liver diseases.Frontiers in immunology · 2023Review
- Dual B-cell targeting therapy ameliorates autoimmune cholangitis.Journal of autoimmunity · 2022Article
- Article
- The Role of B Cells in Adult and Paediatric Liver Injury.Frontiers in immunology · 2021Review
- Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis.Scientific reports · 2020Article
- CD19Mediators of inflammation · 2020Article
- Gal-3 Deficiency SuppressesFrontiers in immunology · 2019Article
- Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.Nature genetics · 2018Article
- Increased Incidence of Post-transplant Lymphoproliferative Disorder in Autoimmune Liver Disease: An Irish National Experience.Journal of clinical and experimental hepatology · 2018Article
- Anti-drug Antibodies Against a Novel Humanized Anti-CD20 Antibody Impair Its Therapeutic Effect on Primary Biliary Cholangitis in Human CD20- and FcγR-Expressing Mice.Frontiers in immunology · 2018Article
- A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization.Scientific reports · 2017Article
- Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.Hepatology (Baltimore, Md.) · 2017Article
- The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis.Cellular & molecular immunology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledThe serologic hallmark of primary biliary cirrhosis (PBC), the antimitochondrial response to the E2 component of the pyruvate dehydrogenase complex (PDC-E2), has unique features, including continuous high titers of immunoglobulin M (IgM) and IgG reactivity throughout all stages of disease, capable not only of target enzyme inhibition, but also crossreactive with chemical xenobiotics that share molecular homology with the inner lipoyl domain of PDC-E2; such chemicals have been proposed as potential etiological agents. We used flow cytometry and enzyme-linked immunospot assay (ELISPOT) to examine B-cell subsets in 59 subjects, including 28 with PBC, 13 with primary sclerosing cholangitis (PSC), and 18 healthy controls. Strikingly, in PBC, although there were no significant differences in B-cell phenotype subpopulations, 10% of the total IgG and IgA plasmablast population and 23% of the IgM plasmablast population were uniquely reactive with PDC-E2, detected in the CXCR7+ CCR10low plasmablast population. In contrast, plasmablast reactivity to a control antigen, tetanus toxoid, was minimal and similar in all groups. Additionally, we isolated plasmablast-derived polyclonal antibodies and compared reactivity with plasma-derived antibodies and noted a distinct noncirculating tissue source of xenobiotic crossreacting antibodies. The high levels of autoantigen specific peripheral plasmablasts indicate recent activation of naive or memory B cells and a continuous and robust activation. The presence of CXCR7+ CCR10low PDC-E2-specific ASCs suggests a mechanistic basis for the migration of circulating antigen specific plasmablasts to the mucosal epithelial ligands CXCL12 and CCL28.
conclusionOur findings suggest a sustained rigorous B-cell response in PBC, likely activated and perpetuated by cognate autoantigen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.