Antimitochondrial Antibodies and Reactivity to N. Aromaticivorans Proteins in Icelandic Patients with Primary Biliary Cirrhosis and Their Relatives

Ólafsson, Sigurđur; Guðjónsson, Hallgrímur; Selmi, Carlo; Amano, Katsushi; Invernizzi, Pietro; Podda, Mauro; Gershwin, Eric

doi:10.1111/j.1572-0241.2004.40397.x

Cited by 49 publications

(36 citation statements)

References 28 publications

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“…The sensitivity is highest in Africans (93.9%), followed by in Asians (88.7%), then in Europeans (81.5%) and lowest in South Americans (75.8%). Different geographical area and selecting cases according to genetic and environmental factors could explain the discrepancy [65,66]. As in the majority of autoimmune diseases, PBC is likely to be genetically complex.…”

Section: Discussionmentioning

confidence: 99%

The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis

Zhao²,

Wang

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:The aim of this study was to evaluate the diagnostic value of anti-mitochondrial antibodies (AMAs) and/or the M2 subtype (AMA-M2) in patients with primary biliary cirrhosis (PBC). AMA/AMA-M2 data were obtained by searching electronic databases. Studies showing AMA/ AMA-M2 results in patients with PBC and control groups with other liver diseases or healthy livers were included. The quality of the involved studies was assessed using the QUADAS tool. The pooled sensitivity and specificity were calculated, and stratified analysis was performed according to possible heterogeneity sources. The pooled AMA (all methods) sensitivity and specificity were 84.5% (95% confidence interval (CI) 83.3%-85.6%) and 97.8% (95% CI 97.6%-98.0%), respectively. The positive and negative likelihood ratios were 25.201 (95% CI 17.583-36.118) and 0.162 (95% CI 0.131-0.199), respectively. The current evidence suggests that AMA and AMA-M2 show favorable accuracy for the diagnosis of PBC with high specificity and sensitivity. AMA is a better and more comprehensive marker than AMA-M2. The accuracy established in this meta-analysis is based on clinical studies using patient cohorts from different ethnicities.Keywords: anti-mitochondrial antibody (AMA); anti-mitochondrial antibody/the M2 subtype (AMA-M2); diagnosis; meta-analysis; primary biliary cirrhosis.

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Section: Discussionmentioning

confidence: 99%

The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis

Zhao²,

Wang

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…14,15 Finally, we have recently demonstrated that patients with PBC from the genetically peculiar population of Iceland did not present similar antimitochondrial patterns, while only one affected relative could be identified among 85 first-degree relatives. 16 Several studies have addressed the hypothesis that less specific immunological disturbances rather than a definitive diagnosis of PBC might in fact be shared by family members of patients. Interestingly, as many as 70% of PBC relatives had some degree of immunological impairment in studies from the early 1970s, 17,18 while somewhat conflicting results came, more recently, from two studies of patterns of immunological disorders in family members.…”

Section: Familial Pbcmentioning

confidence: 99%

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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“…Finally, our group has recently provided serological data suggesting that a ubiquitous xenobiotic-metabolizing Gram-negative bacterium, Novosphingobium aromaticivorans, is the best candidate yet for the induction of PBC, as it elicits a specific antibody reaction (estimated to be 100-to 1,000-fold higher than against E. coli), and its 16S rRNA specific sequences were detected in human fecal samples [38]. Further studies included the reproduction of these data in a distinct cohort of patients [39] and the cloning and sequencing of the four lipoilated proteins from N. aromaticivorans. In this latter case, the phylogenetic relation between this isolated proteins and PBC autoantigens identifies a strong degree of amino acid homology with the known human mitochondrial antigens [40].…”

Section: Xenobiotics and Infectious Agentsmentioning

confidence: 95%

The Chemical Pathway to Primary Biliary Cirrhosis

Selmi

Cocchi

Zuin

et al. 2008

Clinic Rev Allerg Immunol

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Primary biliary cirrhosis (PBC) is a female predominant chronic disease of autoimmune pathogenesis and unknown etiology, although data suggest that genetic predisposition and environmental factors concur to its onset. Among nongenetic factors, several lines of evidence spanning from geoepidemiology to experimental findings support the role of xenobiotics, i.e., chemicals that are capable to induce molecular mimicry through cross reactivity. Indeed, specific xenobiotics are hypothesized to substitute lipoic acid residues on PBC-specific autoepitopes thus triggering autoimmunity. This is supported by data obtained with patient sera reactivities as well as animal models. The scenario is further complicated by the possibility that xenobiotic-metabolizing bacteria might also play a role. We will review the available evidence in this intriguing and rapidly growing field of research and critically discuss its potential implications.

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Antimitochondrial Antibodies and Reactivity to N. Aromaticivorans Proteins in Icelandic Patients with Primary Biliary Cirrhosis and Their Relatives

Abstract: Interestingly, despite the homogenous genetic background, the group of Icelandic patients with PBC was heterogeneous in their AMA reactive patterns and also reacted with N. aromaticivorans proteins.

Cited by 49 publications

References 28 publications

The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis

The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis

Genes and (auto)immunity in primary biliary cirrhosis

The Chemical Pathway to Primary Biliary Cirrhosis

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