ArticleJournal of autoimmunity2011
Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity.
Article in Journal of autoimmunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 47 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
- Detection of Diagnostic Antibodies in Immune-Mediated Diseases: A Focus on Antigens and Technologies.Chembiochem : a European journal of chemical biology · 2026Review
- New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage.World journal of gastroenterology · 2023Review
- Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients.Clinical and experimental immunology · 2021Article
- Identification of a xenobiotic as a potential environmental trigger in primary biliary cholangitis.Journal of hepatology · 2018Article
- Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.Hepatology (Baltimore, Md.) · 2017Article
- The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis.Hepatology (Baltimore, Md.) · 2017Article
- Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update.Journal of managed care & specialty pharmacy · 2016Review
- Environmental Basis of Autoimmunity.Clinical reviews in allergy & immunology · 2016Review
- A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis.Expert review of molecular diagnostics · 2016Review
- Xenobiotics and loss of tolerance in primary biliary cholangitis.World journal of gastroenterology · 2016Review
- The clinical significance of posttranslational modification of autoantigens.Clinical reviews in allergy & immunology · 2014Review
- Environmental factors in primary biliary cirrhosis.Seminars in liver disease · 2014Review
- Antimitochondrial antibody recognition and structural integrity of the inner lipoyl domain of the E2 subunit of pyruvate dehydrogenase complex.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers.Clinical and experimental immunology · 2013Article
- Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary biliary cirrhosis.Hepatology (Baltimore, Md.) · 2013Article
- Environment and primary biliary cirrhosis: electrophilic drugs and the induction of AMA.Journal of autoimmunity · 2013Article
- The X-factor in primary biliary cirrhosis: monosomy X and xenobiotics.Auto- immunity highlights · 2012Review
- Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?Trends in molecular medicine · 2012Article
- Autoimmunity in 2011.Clinical reviews in allergy & immunology · 2012Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC.
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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.