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Patients With Primary Biliary Cirrhosis React Against A Ubiquitous Xenobiotic–Metabolizing Bacterium
Open accessAbstract
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. aromaticivorans and Escherichia coli. The reactivity was defined by absorption, affinity purification, and using monoclonal antibodies to PDC–E2. Stool samples from 20 patients with PBC and 34 controls were analyzed by polymerase chain reaction (PCR) for the presence of N. aromaticivorans. Sera from 100% of anti–PDC–E2 positive (77/77), 33% of anti–BCOADC E2 positive (1/3), and 12% of antimitochondrial antibody (AMA) negative patients with PBC (2/17) reacted with titers up to 10-6 against two known lipoylated bacterial proteins (47 and 50 kd) from N. aromaticivorans, including patients with early disease. This titer was approximately 100– to 1,000–fold higher than against E. coli and verified by absorption, use of affinity–purified sera, and monoclonal antibody reagents. Moreover, 78 of 80 AMA–positive and 5 of 17 AMA–negative patients with PBC had antibodies against 3 other N. aromaticivorans proteins. In contrast, 0 of 195 control sera reacted against N. aromaticivorans. Approximately 25% of patients and controls had N. aromaticivorans in their fecal specimens. In conclusion, based on protein homology, capacity to metabolize xenobiotics as well as modulate estrogens, its presence in feces, and specific immunologic response, we propose that N. aromaticivorans is a candidate for the induction of PBC.
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“The existence of disease clustering points to environmental triggers, and research has supported both infectious and chemical triggers.22 28 57–61”
From The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018) · cites this paper as [61]
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Metadata
- Authors
- Selmi, C., Balkwill, D. L., Invernizzi, P., Ansari, A. A., Coppel, R. L., Podda, M., Leung, P. S., Kenny, T. P., Van De Water, J., Nantz, M. H., Kurth, M. J., & Gershwin, E. M.
- Affiliations
- University of Milan (IT)
- Florida State University (US)
- Emory University (US)
- Monash University (AU)
- University of California, Davis (US)
- Corresponding author
- Gershwin, Eric M.
- ORCID
- Venue
- Hepatology
- Published
- 2003-11
- Volume
- 38
- Issue
- 5
- Pages
- 1250-1257
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2151434633
- Cited by
- 312
- References
- 38
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 11 · 2022: 10 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 14 · 2017: 4 · 2016: 4 · 2015: 16 · 2014: 9 · 2013: 25 · 2012: 19
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK 39588)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 39588)
- National Institute of Environmental Health Sciences (ES103019)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- primary biliary cirrhosis, Novosphingobium aromaticivorans, autoantibodies, pyruvate dehydrogenase E2, antimitochondrial antibodies, fecal bacteria, Escherichia coli
- MeSH terms
- Amino Acid Sequence, Bacterial Infections, Bacterial Proteins, Feces, Female, Humans, Liver Cirrhosis, Biliary, Male, Molecular Sequence Data, Pyruvate Dehydrogenase Complex, Xenobiotics, Case-Control Studies, Sequence Homology, Amino Acid, Molecular Mimicry, Alphaproteobacteria, Dihydrolipoyllysine-Residue Acetyltransferase
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