Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic‐metabolizing bacterium

@article{Selmi2003PatientsWP,
  title={Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic‐metabolizing bacterium},
  author={Carlo Selmi and David L. Balkwill and Pietro Invernizzi and Aftab A. Ansari and Ross L. Coppel and Mauro Podda and Patrick S. C. Leung and Thomas P. Kenny and Judy A. Van de Water and Michael H. Nantz and Mark J Kurth and Merrill Eric Gershwin},
  journal={Hepatology},
  year={2003},
  volume={38}
}
Infectious and environmental agents have been proposed as immunologic triggers for primary biliary cirrhosis (PBC). Recently, a ubiquitous organism that metabolizes organic compounds and estrogens, Novosphingobium aromaticivorans, has been defined. Importantly, 2 bacterial proteins have homology with the E2 component of the pyruvate dehydrogenase complex (PDC‐E2). Sera from 97 patients with PBC, 46 first‐degree relatives, 10 spouses, and 195 controls were studied for reactivity against N… 
Serum Reactivity Against Bacterial Pyruvate Dehydrogenase: Increasing the Specificity of Anti-Mitochondrial Antibodies for the Diagnosis of Primary Biliary Cirrhosis
TLDR
It is demonstrated that weak cross-reactivity with E. coli PDC-E2 occurs in non-PBC sera at lower dilutions and that such reactivity is not due to AMA-positivity, and the use of a specific buffer could reduce non-specific serum reactivity.
Antimitochondrial Antibodies and Reactivity to N. Aromaticivorans Proteins in Icelandic Patients with Primary Biliary Cirrhosis and Their Relatives
TLDR
Interestingly, despite the homogenous genetic background, the group of Icelandic patients with PBC was heterogeneous in their AMA reactive patterns and also reacted with N. aromaticivorans proteins.
Xenobiotics and autoimmunity: does acetaminophen cause primary biliary cirrhosis?
TLDR
Quantitative structure-activity relationship (QSAR) data indicates that acetaminophen metabolites are particularly immunoreactive with AMA, and it is submitted that in genetically susceptible hosts, electrophilic modification of lipoic acid in PDC-E2 byacetaminophen or similar drugs can facilitate a loss of tolerance and lead to the development of PBC.
Pathogen infections and primary biliary cholangitis
TLDR
Multiple mechanisms can result in the loss of tolerance to mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably one of the dominant pathways, especially in female patients, and improving environmental hygiene and increased prevalence of PBC, may argue against the aetiological role of bacterial infection.
Primary biliary cirrhosis following Lactobacillus vaccination for recurrent vaginitis.
TLDR
It is concluded that lactobacillus vaccination therapy may be another culprit for the development of PBC in genetically susceptible women.
Chemical Xenobiotics and Mitochondrial Autoantigens in Primary Biliary Cirrhosis: Identification of Antibodies against a Common Environmental, Cosmetic, and Food Additive, 2-Octynoic Acid 1
TLDR
It is hypothesized that in PBC the lipoyl domain of the immunodominant E2 component of pyruvate dehydrogenase (PDC-E2) is replaced by a chemical xenobiotic mimic, which is sufficient to break self-tolerance.
Environment and primary biliary cirrhosis: electrophilic drugs and the induction of AMA.
TLDR
It is postulated that chemical xenobiotics modification of the lipoyl domain of PDC-E2 is sufficient to break self-tolerance, with subsequent production of AMA in patients with PBC, and data on the immunological characterization of antigen and Ig isotype specificities against one such lipoic acid mimic strongly support a xenobiotic etiology in PBC.
Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic
TLDR
IgG3 antibodies to BGAL LACDE cross‐react with the major mitochondrial autoepitope and are characteristic of PBC.
Xenobiotic Induced Model of Primary Biliary Cirrhosis
TLDR
Th is model of xenobiotic induced PBC is suitable for studying the early events in PBC pathogenesis and for developing new therapeutics in P BC.
The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis
TLDR
It is demonstrated that the conformation of PDC‐E2 ILD is altered when conjugated with 2OA, compared to conjugation with lipoic acid, which is critical for understanding xenobiotic modification and loss of tolerance in PBC.
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TLDR
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TLDR
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  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
In vivo and in vitro, it is found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture, and the human betaretrovirus is referred to as the putative agent because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue.
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TLDR
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