Augmentation of the Antibody Response by Lipoic Acid in Mice II. Restoration of the Antibody Response in Immunosuppressed Mice

Ohmori, Hitoshi; Yamauchi, Toshihiko; Yamamoto, Ichiro

doi:10.1254/jjp.42.275

Cited by 16 publications

(5 citation statements)

References 13 publications

(9 reference statements)

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“…Lipoic acid has been shown to be a mitogen, augmenting antibody responses in vitro [20] and restoring antibody responses in immunosuppressed mice [21]. The finding that the immunodominant region is located within the lipoyl-containing domain prompted us to investigate the possible role of lipoic acid in antibody binding.…”

Section: Resultsmentioning

confidence: 99%

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

et al. 1989

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Autoantibodies in the sera of patients with primary biliary cirrhosis, shown previously to recognise the E2 polypeptide of the mammalian pyruvate dehydrogenase complex (PDC), have been demonstrated to react with the E2 component of PDC from bacteria (E. coli) and yeast (S. cerevisiae). Limited tryptic digestion, which cleaves E2 into well-characterised domains, followed by Western blotting indicates that the main immunodominant region of PDC E2 lies within the lipoic acid-containing domains of the polypeptide.

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Section: Resultsmentioning

confidence: 99%

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

et al. 1989

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“…3). The E-3 binding domains contain a 36 mammalian lipoamide dehydrogenase (E3) will not only complement the overall pyruvate dehydrogenase complex activity of lpd (E3) mutants of E. coli in a coupled enzyme reaction (34) but also will bind to the E1-E2 partial complexes in extracts of cross-reacting material-negative Ipd mutants to produce an active high molecular mass complex (I. T. Creaghan and J.R.G., unpublished observations). The longest and most highly conserved region of sustained homology between E2p.R and E2p.E is in a 123-residue segment of the innercore domains where 40o of the residues are identical and a further 32% are conservatively substituted at the 0.1 scoring limit of MDM (Fig.…”

Section: Comparison Of Mammalian Andmentioning

confidence: 99%

Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis.

Fussey

Guest

James

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

244

102

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Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial antibodies in the serum. It is possible that the PBC-specific immunoreactive trypsin-sensitive antigens on the inner mitochondrial membrane, termed M2, are important in the pathogenesis of this autoimmune disease. We have previously shown that a major M2"a" antigen is the E2 component of the pyruvate dehydrogenase multienzyme complex located within mitochondria. Analysis of the primary structure of the E2 components of all three 2-oxo acid dehydrogenase complexes reveals a high degree of homology with a similar highly segmented structure including lipoyl domains, E3-binding domains, C-terminal catalytic domains, and interdomain linker sequences. Immunoblotting of PBC patients' sera against purified E2 protein from 2-oxoglutarate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex reveals that these polypeptides are also autoantigens in this disease. Sera from 29 of 40 (72.5%) PBC patients gave a positive response against bovine 2-oxoglutarate dehydrogenase complex E2 and from 25 of 40 (62.5%) PBC patients gave a positive response against bovine branched-chain 2-oxo acid dehydrogenase complex E2. All 40 PBC patients (100%) have autoantibodies directed against at least one of the E2 components of the family of 2-oxo acid dehydrogenase complexes.

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“…Lipoic acid is known to stimulate antibody responses both in vitro (10) and in immunosuppressed mice (11). The presence of at least one lipoyl moiety in all E2 components (and protein X) suggests that lipoate may have a role to play in the "autoimmune" response to these proteins.…”

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confidence: 99%

Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region.

Fussey

Ali

Guest

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

136

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Primary bilary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2-oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoyl domains; (ii) the presence of a lipoyl residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These rmdings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group.

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Augmentation of the Antibody Response by Lipoic Acid in Mice II. Restoration of the Antibody Response in Immunosuppressed Mice

Abstract: Abstract-Lipoic acid (Lip) was examined for its effect on the in vivo antibody response in mice.

Cited by 16 publications

References 13 publications

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

Characterisation of the reactivity of autoantibodies in primary biliary cirrhosis

Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis.

Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region.

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