The peculiar autoimmunity of primary biliary cirrhosis

  title={The peculiar autoimmunity of primary biliary cirrhosis},
  author={Ian R. Mackay and Senga Whittingham and Shahnaz Fida and Mark A. Myers and Nobuhiro Ikuno and Merrill Eric Gershwin},
  journal={Immunological Reviews},
Summary: Autoantibodies to mitochondria (AMA, anti‐M2) are a serologic hallmark of primary biliary cirrhosis (PBC). These react with three structurally and functionally related multienzymic complexes, the 2‐oxoacid dehydrogenase complexes, but chiefly with the E2 subunit of pyruvate dehydrogenase complex (PDC‐E2). Their very close (95%) and specific association with PBC underpins the autoimmune concept of pathogenesis of that disease, notwithstanding several non‐congruent features. Detailed… 
Autoimmunity and primary biliary cirrhosis.
  • I. Mackay
  • Biology, Medicine
    Bailliere's best practice & research. Clinical gastroenterology
  • 2000
An accumulation uniquely in PBC of PDC-E2-like material at the plasma membrance of biliary epithelial cells (BECs) provides a credible 'tissue-specific' target for an autoimmune attack by T and B lymphocytes at the site of the actual pathology.
Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients
It is hypothesized that AMAs and their antigens formed ICs in PBC sera, and sera of PBC and four autoimmune diseases are analyzed using immune complexome analysis, in which ICs are separated from serum and are identified by nano‐liquid chromatography‐tandem mass spectrometry.
Etiopathogenesis of primary biliary cirrhosis: an overview of recent developments
Key advances in the field of primary biliary cirrhosis research are summarized as the true complexities of the disease process begin to be unraveled.
The causes of primary biliary cirrhosis: Convenient and inconvenient truths
It is emphasized that the potential initiator of PBC includes inter alia particular environmental xenobiotics; pathogenesis is aided and abetted by genetic weaknesses in mechanisms of immune regulation; and subsequent multilineage immunopathology impacts upon uniquely susceptible BECs to culminate clinically in the chronic autoimmune cholangiolitis of P BC.
Molecular diagnostics of primary biliary cirrhosis.
Critical analysis of all published data regarding PBC serology between 1985 and 2007 was performed in order to suggest a diagnostic algorithm for the serological diagnosis of PBC, and molecular-based assays have been developed for the detection of P BC-specific ANA.
Antimitochondrial Antibodies and Reactivity to N. Aromaticivorans Proteins in Icelandic Patients with Primary Biliary Cirrhosis and Their Relatives
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.
Etiopathogenesis of primary biliary cirrhosis.
The available evidence on etiopathogenesis of PBC is critically reviewed and interpretations of complex data, new developments and theories, and nominate directions for future research are presented.
The immunobiology and pathophysiology of primary biliary cirrhosis.
A better understanding of the mechanism for selective biliary cell destruction is resulted and genome-wide association studies suggest an important role for the IL-12 pathway in disease susceptibility.
Antimitochondrial and other autoantibodies.


Antimitochondrial antibodies in primary biliary cirrhosis.
increasing evidence, including the specific association of AMA with PBC, suggests that AMA is not an epiphenomenon of the disease but plays a significant role in the pathogenesis of PBC.
The association of primary biliary cirrhosis and systemic sclerosis is not accounted for by cross reactivity between mitochondrial and centromere antigens.
Antitochondrial antibodies and anticentromere antibodies present discrete autoantibody populations which may coexist in the same patient and may influence the clinical picture but have both structural and immunologically independent antigenic targets.
Primary biliary cirrhosis: an orchestrated immune response against epithelial cells
The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.
Primary biliary cirrhosis: paradigm or paradox for autoimmunity.
The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase
A 603-bp fragment that codes for a polypeptide containing all of the autoreactivity of the original rat liver cDNA clone is identified and it appears that for this autoantigen, the target of the autoantibodies corresponds to a functional site of the dihydrolipoamide acetyltransferase.
Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region.
It is indicated 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 thelipoyl cofactor with an octanoyl group.
Three-dimensional structure of the major autoantigen in primary biliary cirrhosis.
Autoantibodies against "nuclear dots" in primary biliary cirrhosis.
Knowledge on the structure and putative function of two nuclear autoantigens, the Sp100 and PML proteins, which are present in so-called nuclear dots (NDs) and against which autoantibodies arepresent in a subpopulation of PBC patients are summarized.
The predominance of IgG3 and IgM isotype antimitochondrial autoantibodies against recombinant fused mitochondrial polypeptide in patients with primary biliary cirrhosis
It is reported that IgG3 is the predominant isotype of antimitochondrial autoantibodies in a group of 74 primary biliary cirrhosis patients, significant in light of the genomic im‐munoglobulin in heavy chain gene arrangement.
Natural and disease associated autoantibodies to the autoantigen, dihydrolipoamide acetyltransferase, recognise different epitopes.
Naturally occurring autoantibodies are ubiquitous and may serve physiological functions. We examined the relationship of natural and disease-associated autoantibodies in the context of autoantibodies