Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis

Kerstien A. Padgett, Carlo Selmi, Thomas P. Kenny, Patrick S C Leung, David L. Balkwill, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Novosphingobium aromaticivorans, a unique ubiquitous bacterium that metabolizes xenobiotics and activates environmental estrogens, has been suggested as a pathogenic factor in the development of primary biliary cirrhosis (PBC). To define the molecular basis of PBC sera reactivity, we investigated the characteristic of the bacterial antigens involved. We cloned and sequenced four genes from N. aromaticivorans coding for immunoreactive proteins, arbitrarily named Novo 1 through Novo 4. We subsequently analyzed these proteins for their homology to known mitochondrial proteins and defined their reactivity using monoclonal antibodies (mAbs), rabbit anti-lipoic acid antibody, and PBC/control sera. Moreover, we studied their phylogenetic relation with the known PBC autoantigens. Novo proteins have an extraordinary degree of amino acid homology with all of the major human mitochondrial autoantigens PDC-E2 (Novo 1 and 2), OGDC-E2 (Novo 3), and BCOADC-E2 (Novo 4). Moreover, Novo 1-4 contain a lipoylated domain, are recognized by AMA-positive sera, and react with specific mAbs to mitochondrial antigens. Interestingly, the phylogenetic relation of the proteins emphasizes the conservation of the lipoylated domain. In conclusion, our data provide a high degree of confidence that N. aromaticivorans may potentiate the breakdown of self tolerance in genetically susceptible individuals.

Original languageEnglish
Pages (from-to)209-219
Number of pages11
JournalJournal of Autoimmunity
Volume24
Issue number3
DOIs
Publication statusPublished - May 2005

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Biliary Liver Cirrhosis
dihydrolipoamide succinyltransferase
Autoantigens
Proteins
Serum
Monoclonal Antibodies
Bacterial Antigens
Self Tolerance
Thioctic Acid
Mitochondrial Proteins
Xenobiotics
Estrogens
Rabbits
Bacteria
Antigens
Amino Acids
Antibodies
Genes

Keywords

  • Lipoic acid
  • Molecular mimicry
  • Protein homology
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis. / Padgett, Kerstien A.; Selmi, Carlo; Kenny, Thomas P.; Leung, Patrick S C; Balkwill, David L.; Ansari, Aftab A.; Coppel, Ross L.; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 24, No. 3, 05.2005, p. 209-219.

Research output: Contribution to journalArticle

Padgett, Kerstien A. ; Selmi, Carlo ; Kenny, Thomas P. ; Leung, Patrick S C ; Balkwill, David L. ; Ansari, Aftab A. ; Coppel, Ross L. ; Gershwin, M. Eric. / Phylogenetic and immunological definition of four lipoylated proteins from Novosphingobium aromaticivorans, implications for primary biliary cirrhosis. In: Journal of Autoimmunity. 2005 ; Vol. 24, No. 3. pp. 209-219.
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