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Autoantibodies in autoimmune liver disease: biomarkers versus epiphenomena
  1. Carlo Selmi1,
  2. M Eric Gershwin2
  1. 1Department of Medicine, IRCCS Istituto Clinico Humanitas, University of Milan, Italy
  2. 2Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, California, USA
  1. Correspondence to Professor M Eric Gershwin, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, GBSF suite 6510, 451 E Health Sciences Drive, Davis, CA 95616, USA; megershwin{at}ucdavis.edu

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Serum autoantibodies have steadily established themselves as critical biomarkers for the diagnosis of autoimmune diseases. This is well illustrated in the case of primary biliary cirrhosis (PBC) in which antimitochondrial antibodies (AMAs) are a major diagnostic criterion, being both sensitive and specific, despite lacking prognostic significance. The mitochondrial autoantigen was identified >20 years ago1 and rigorous dissection of the immune response subsequently led to the development of molecular methods to increase the test specificity and sensitivity, and the identification of autoreactive CD4 and CD8 cells. This example of AMAs reminds us that the recognition of an autoantigen can become a milestone in understanding the disease. This paradigm may well be illustrated in data described in this issue of Gut by Terjung and colleagues (see page 808). In this report, the authors demonstrate that β tubulin isotype 5 (TBB-5), the atypical pANCA autoantigen, further suggesting that the TBB-5 bacterial precursor FtsZ leads to tolerance breakdown and chronic inflammation.2

The history of autoantibodies reactive with the cytoplasm of neutrophils (ANCAs) has been a difficult and conflicting field. Similar to antinuclear antibodies, ANCAs are a non-uniform family of antibodies recognising diverse cytoplasmic constituents of human neutrophilic …

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