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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jun 7, 2008; 14(21): 3374-3387
Published online Jun 7, 2008. doi: 10.3748/wjg.14.3374
Autoimmune liver serology: Current diagnostic and clinical challenges
Dimitrios P Bogdanos, Pietro Invernizzi, Ian R Mackay, Diego Vergani
Dimitrios P Bogdanos, Diego Vergani, Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill Campus, London SE5 9RS, United Kingdom
Pietro Invernizzi, Division of Internal Medicine and Liver Unit, San Paolo Hospital School of Medicine, University of Milan, Milan 20142, Italy
Ian R Mackay, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
Correspondence to: Diego Vergani, Professor, Institute of Liver Studies, King’s College London School of Medicine at King’s College Hospital, Denmark Hill Campus, London SE5 9RS, United Kingdom. diego.vergani@kcl.ac.uk
Telephone: +44-20-32993305
Fax: +44-20-32993700
Received: March 20, 2008
Revised: April 12, 2008
Accepted: April 19, 2008
Published online: June 7, 2008
Abstract

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians’ requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Keywords: Autoantigen, Autoimmune hepatitis, Autoantibody, Primary biliary cirrhosis, Primary sclerosing cholangitis, Liver disease