Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium

Carlo Selmi, David L. Balkwill, Pietro Invernizzi, Aftab A. Ansari, Ross L. Coppel, Mauro Podda, Patrick S Leung, Thomas P. Kenny, Judith A Van de Water, Michael H. Nantz, Mark J. Kurth, M. Eric Gershwin

Research output: Contribution to journalArticle

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Abstract

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. Importandy, 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-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.

Original languageEnglish (US)
Pages (from-to)1250-1257
Number of pages8
JournalHepatology
Volume38
Issue number5
DOIs
StatePublished - Nov 2003

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Biliary Liver Cirrhosis
Xenobiotics
Bacteria
Bacterial Proteins
Serum
Antibodies
Estrogens
Dihydrolipoyllysine-Residue Acetyltransferase
Monoclonal Antibodies
Escherichia coli
Spouses
Feces
Proteins
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hepatology

Cite this

Selmi, C., Balkwill, D. L., Invernizzi, P., Ansari, A. A., Coppel, R. L., Podda, M., ... Gershwin, M. E. (2003). Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium. Hepatology, 38(5), 1250-1257. https://doi.org/10.1053/jhep.2003.50446

Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium. / Selmi, Carlo; Balkwill, David L.; Invernizzi, Pietro; Ansari, Aftab A.; Coppel, Ross L.; Podda, Mauro; Leung, Patrick S; Kenny, Thomas P.; Van de Water, Judith A; Nantz, Michael H.; Kurth, Mark J.; Gershwin, M. Eric.

In: Hepatology, Vol. 38, No. 5, 11.2003, p. 1250-1257.

Research output: Contribution to journalArticle

Selmi, C, Balkwill, DL, Invernizzi, P, Ansari, AA, Coppel, RL, Podda, M, Leung, PS, Kenny, TP, Van de Water, JA, Nantz, MH, Kurth, MJ & Gershwin, ME 2003, 'Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium', Hepatology, vol. 38, no. 5, pp. 1250-1257. https://doi.org/10.1053/jhep.2003.50446
Selmi C, Balkwill DL, Invernizzi P, Ansari AA, Coppel RL, Podda M et al. Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium. Hepatology. 2003 Nov;38(5):1250-1257. https://doi.org/10.1053/jhep.2003.50446
Selmi, Carlo ; Balkwill, David L. ; Invernizzi, Pietro ; Ansari, Aftab A. ; Coppel, Ross L. ; Podda, Mauro ; Leung, Patrick S ; Kenny, Thomas P. ; Van de Water, Judith A ; Nantz, Michael H. ; Kurth, Mark J. ; Gershwin, M. Eric. / Patients With Primary Biliary Cirrhosis React Against a Ubiquitous Xenobiotic-Metabolizing Bacterium. In: Hepatology. 2003 ; Vol. 38, No. 5. pp. 1250-1257.
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abstract = "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. Importandy, 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-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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