BACKGROUND/AIMS: Antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex, PDC-E2, and other mitochondrial 2-oxoacid dehydrogenases (AMA-M2) are the hallmark for diagnosis of primary biliary cirrhosis (PBC). AMA-M2 formation as an early step in the pathogenesis of PBC has recently been assumed to be triggered by bacterial mimics of the E2 subunit and certain reactant xenobiotics. We report a case of symptomatic PBC diagnosed after sequential immunization with a lactobacillus vaccine for recurrent vaginitis over years. METHODS: Serum AMA-M2 specificity of the patient was evaluated by indirect immunofluorescence, immunoblotting and ELISA. Serum antibody responses against pyruvate dehydrogenase complex-E2 subunit (PDC-E2(212-226)), the major PBC-specific mitochondrial autoepitope, and microbial mimics revealed cross-reactivity with beta-galactosidase of Lactobacillus delbrueckii (LACDE BGAL(266-280)) which shows a high local homology with that of Lactobacillus species administered via the vaccine. The relative affinity of antibody reactivity to LACDE BGAL(266-280) was significantly higher than that against human PDC-E2(212-226). CONCLUSIONS: We conclude that lactobacillus vaccination therapy may be another culprit for the development of PBC in genetically susceptible women.
BACKGROUND/AIMS: Antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex, PDC-E2, and other mitochondrial 2-oxoacid dehydrogenases (AMA-M2) are the hallmark for diagnosis of primary biliary cirrhosis (PBC). AMA-M2 formation as an early step in the pathogenesis of PBC has recently been assumed to be triggered by bacterial mimics of the E2 subunit and certain reactant xenobiotics. We report a case of symptomatic PBC diagnosed after sequential immunization with a lactobacillus vaccine for recurrent vaginitis over years. METHODS: Serum AMA-M2 specificity of the patient was evaluated by indirect immunofluorescence, immunoblotting and ELISA. Serum antibody responses against pyruvate dehydrogenase complex-E2 subunit (PDC-E2(212-226)), the major PBC-specific mitochondrial autoepitope, and microbial mimics revealed cross-reactivity with beta-galactosidase of Lactobacillus delbrueckii (LACDE BGAL(266-280)) which shows a high local homology with that of Lactobacillus species administered via the vaccine. The relative affinity of antibody reactivity to LACDE BGAL(266-280) was significantly higher than that against humanPDC-E2(212-226). CONCLUSIONS: We conclude that lactobacillus vaccination therapy may be another culprit for the development of PBC in genetically susceptible women.
Authors: Daniel Smyk; Eirini I Rigopoulou; Harold Baum; Andrew K Burroughs; Diego Vergani; Dimitrios P Bogdanos Journal: Clin Rev Allergy Immunol Date: 2012-04 Impact factor: 8.667
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Authors: Jinjun Wang; Madhu S Budamagunta; John C Voss; Mark J Kurth; Kit S Lam; Ling Lu; Thomas P Kenny; Christopher Bowlus; Kentaro Kikuchi; Ross L Coppel; Aftab A Ansari; M Eric Gershwin; Patrick S C Leung Journal: J Immunol Date: 2013-07-26 Impact factor: 5.422
Authors: Daniel S Smyk; Dimitrios P Bogdanos; Albert Pares; Christos Liaskos; Charalambos Billinis; Andrew K Burroughs; Eirini I Rigopoulou Journal: Tuberc Res Treat Date: 2012-10-30