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

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

doi:10.1016/j.jaut.2005.01.012

Cited by 95 publications

(65 citation statements)

References 37 publications

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“…First, the aminoacid sequences of four different proteins from N. aromaticivorans present one of the highest degrees of homology with the main AMA autoepitopes. 143 This has been confirmed by the cloning, sequencing, and expression of these four proteins by Padgett et al 144 that also defined the recombinant proteins using well-defined monoclonal antibodies. Second, although first isolated from sewage samples, N. aromaticivorans can be found in several environmental media, including water.…”

Section: Molecular Mimicrymentioning

confidence: 74%

Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strenghtens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.

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Section: Molecular Mimicrymentioning

confidence: 74%

Genes and (auto)immunity in primary biliary cirrhosis

et al. 2005

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“…Notwithstanding a substantial shared sequence homology, in a fewer cases a cross reactivity by 2-OADC-specific autoantibodies and/or T cells has been also demonstrated. This is the case for Escherichia coli [100,101,103], Novosphingobium aromaticivorans [32,104,105], Salmonella Minnesota [106], Pseudomonas aeruginosa [107], Haemophilus influenzae [103], Yersinia enterocolitica [103], Streptococcus intermedius [108], Lactobacillus delbrueckii [109], Paracoccus denitrificans [110], Mycoplasma [111,112], Mycobacterium gordonae [113], Borrelia burgdorferi [114], Trypanosomes [115], and Ascaridia galli [115] (Table 1). Moreover, microbial antigens or DNA have been found in liver specimens, gallbladder bile, and fecal samples of patients with PBC as for N. aromaticivorans [104], Propionibacterium acnes [116], and Epstein Barr virus [117].…”

Section: Infectious Agents: Numerous Studies Limited Evidencementioning

confidence: 98%

“…Taken together these studies suggest that multiple agents and multiple mechanisms could be involved in the pathogenesis of PBC. Interestingly, among microbial pathogens N. aromaticivorans is supported by the most solid data, considering also its ability to metabolize halogenated compounds [32,104,105,118].…”

Section: Chlamydia Pneumoniaementioning

confidence: 99%

“…The mitochondrial antigens recognized by both B and T cell autoimmune responses in PBC are ubiquitously expressed in nucleated cells and highly conserved in phylogenesis [32]. It has been proven that mitochondrial antigens are not cryptic to the immune system and that the immune system is normally tolerant to mitochondrial self-antigens, even if responsive against bacterial homologues.…”

Section: The Immunobiology Of the Biliary Epitheliummentioning

confidence: 99%

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Infectious Agents and Xenobiotics in the Etiology of Primary Biliary Cirrhosis

et al. 2010

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Abstract. Primary biliary cirrhosis (PBC)is a chronic autoimmune cholestatic liver disease that manifests a latitudinal gradient in prevalence and incidence. The mechanisms leading to the initiation and perpetuation of PBC remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. PBC is also characterized by a high concordance rate in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. From a diagnostic standpoint, PBC is characterized by the highest specificity of serum autoantibodies directed at mitochondrial proteins. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics that will be critically discussed in the present review article.

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“…The reactivity against PDC-E2 is also 100 to 1000 fold greater than that seen with E. coli antigens. One study showed 100% reactivity with the bacterium in PBC patients compared to none in the control group [32]. Another study demonstrated that autoreactive AMA and T-cell mediated autoimmunity can be induced in the biliary ducts after immunization with this bacterium [33].…”

Section: Microbial Exposurementioning

confidence: 99%

Primary Biliary Cirrhosis: Environmental Risk Factors

2010

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Abstract. Primary biliary cirrhosis (PBC) is an autoimmune disease of unclear etiology. It is a chronic, progressive condition that causes intrahepatic ductal destruction ultimately leading to symptoms of cholestasis, cirrhosis and liver failure. The disease predominantly affects middle aged Caucasian women. It has a predilection to certain regions and is found in higher incidences in North America and Northern Europe. It also has a genetic predisposition with a concordance rate of 60% among monozygotic twins. Combinations of genetic and environmental factors are proposed in the pathogenesis of this disease with a compelling body of evidence that suggests a role for both these factors. This review will elucidate data on the proposed environmental agents involved the disease's pathogenesis including xenobiotic and microbial exposure and present some of the supporting epidemiologic data.

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

Cited by 95 publications

References 37 publications

Genes and (auto)immunity in primary biliary cirrhosis

Genes and (auto)immunity in primary biliary cirrhosis

Infectious Agents and Xenobiotics in the Etiology of Primary Biliary Cirrhosis

Primary Biliary Cirrhosis: Environmental Risk Factors

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