Antimitochondrial and other autoantibodies

Bogdanos, Dimitrios P.; Baum, Harold; Vergani, Diego

doi:10.1016/s1089-3261(03)00104-1

Cited by 99 publications

(135 citation statements)

References 112 publications

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“…34 These include Sp100 and PML proteins, which generate a nuclear dot staining pattern, and two components of the NPC specifically associated with a perinuclear pattern (i.e., gp210, and p62). In recent years, the clinical significance of ANA in PBC has been widely investigated and data seem to indicate that, different from AMA, 35 PBC-specific ANA correlate with disease severity in crosssectional studies. 34 NOTE.…”

Section: Discussionmentioning

confidence: 99%

Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

et al. 2006

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Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15-year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti-NPC(؉) patients (26% vs. 5%, P ‫؍‬ .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In conclusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression. (HEPATOLOGY 2006;43:1135-1144

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Section: Discussionmentioning

confidence: 99%

Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

et al. 2006

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“…To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells P rimary biliary cirrhosis (PBC) is a chronic inflammatory cholestatic disease of unknown origin that affects small and medium intrahepatic bile ducts. 1 A wide range of data suggest an autoimmune pathogenesis for the disease, mostly based on the presence of serum anti-mitochondrial autoantibodies (AMAs) 2 and autoreactive T cells directed against the same autoantigens. 3 Infectious agents have been proposed as triggers in susceptible individuals through a mechanism known as molecular mimicry.…”

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confidence: 99%

Altered Monocyte Responses to Defined TLR Ligands in Patients With Primary Biliary Cirrhosis *

et al. 2005

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The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (

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“…1 Antimitochondrial antibodies (AMAs) directed against subunits of the 2-oxo-acid dehydrogenase complexes (OADC, collectively named M2) are a prominent feature of the disease. 2 The immunodominant target of the AMAs is the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). 2,3 The principal B-cell [3][4][5] and T-cell 6,7 PDC-E2 epitopes have shown to colocalize within the inner lipoyl-binding domain of the subunit, overlapping amino acid 212-226 (PDC-E2 212-226 ), a region physically exposed on the molecule's surface.…”

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confidence: 99%

“…2 The immunodominant target of the AMAs is the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). 2,3 The principal B-cell [3][4][5] and T-cell 6,7 PDC-E2 epitopes have shown to colocalize within the inner lipoyl-binding domain of the subunit, overlapping amino acid 212-226 (PDC-E2 212-226 ), a region physically exposed on the molecule's surface. 8 The stimulus responsible for the breakdown of immunological tolerance and the development of autoimmune responses against this short sequence of PDC-E2 is still unclear.…”

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confidence: 99%

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic†

et al. 2005

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The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2 212-226 and hsp's is a cross-reactive target. Having found that this same motif is present only in ␤-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to crossreactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL 266-280 LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57%) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12%; P < .001) had anti-BGAL 266-280 antibodies, mainly of the IgG4 subclass. ECOLI PDC-E2 reactivity was virtually absent. BGAL 266-280 /PDC-E2 212-226 reactivity of the IgG3 isotype was found in 52 (52%) AMA-positive PBC patients but in only 1 of the controls (P < .001). LACDE BGAL 266-280 /PDC-E2 212-226 reactivity was due to crossreactivity as confirmed via competition ELISA. Antibody affinity for BGAL 266-280 was greater than for PDC-E2 mimics. Preincubation of a multireactive serum with BGAL 266-280 reduced the inhibition of enzymatic activity by 40%, while marginal effect (12%) or no effect (2%) was observed in human or ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.

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Antimitochondrial and other autoantibodies

Cited by 99 publications

References 112 publications

Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

Altered Monocyte Responses to Defined TLR Ligands in Patients With Primary Biliary Cirrhosis *

Primary biliary cirrhosis is characterized by IgG3 antibodies cross‐reactive with the major mitochondrial autoepitope and its Lactobacillus mimic†

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