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Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis

Authors

  • Eirini I. Rigopoulou,

    1. Academic Liver Unit and Research Laboratory of Internal Medicine, Department of Medicine, University of Thessaly, Larissa, Greece
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    • *These Authors contributed equally.

  • Edward T. Davies,

    1. Department of Immunology, King's College London School of Medicine at King's College Hospital, London, UK
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    • *These Authors contributed equally.

  • Dimitrios-Petrou Bogdanos,

    1. Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK
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    • *These Authors contributed equally.

  • Christos Liaskos,

    1. Academic Liver Unit and Research Laboratory of Internal Medicine, Department of Medicine, University of Thessaly, Larissa, Greece
    2. Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK
    3. Centre for Research and Technology-Thessaly (CERETETH), Institute of Biomedical Technology (BIOMED), Larissa, Greece
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  • Maria Mytilinaiou,

    1. Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK
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  • George K. Koukoulis,

    1. Department of Pathology, Larissa Medical School, University of Thessaly, Larissa, Greece
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  • George N. Dalekos,

    1. Academic Liver Unit and Research Laboratory of Internal Medicine, Department of Medicine, University of Thessaly, Larissa, Greece
    2. Centre for Research and Technology-Thessaly (CERETETH), Institute of Biomedical Technology (BIOMED), Larissa, Greece
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  • Diego Vergani

    1. Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UK
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Correspondence
Professor Diego Vergani, Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK
Tel: +44 203 299 3305
Fax: +44 203 299 3700
e-mail: diego.vergani@kcl.ac.uk

Abstract

Background/Aims: Primary biliary cirrhosis (PBC) is characterised by the presence of immunoglobulin (Ig) G antimitochondrial antibodies (AMA), which are routinely detected by indirect immunofluorescence (IFL) using composite rodent tissue substrate. The IgG subclass distribution and clinical significance of IFL-detected AMA in patients with PBC have not been previously studied in detail.

Methods: We have examined IgG subclass-specific AMA detected by IFL on rodent liver, kidney and stomach tissue substrate using affinity-purified IgG subclass monospecific antisera as revealing reagents in 95 AMA-positive PBC patients from Greece.

Results: AMA of any of the IgG1, IgG2 or IgG3 subclasses were present in 89/95 (93.7%) patients. Among those 89, 55 (61.8%) had IgG1, 2, 3 AMA positivity; eight (9%) had IgG1, 2; seven (7.9%) had IgG2, 3; eight (9%) had IgG1, 3; nine (10.1%) had IgG1 subclass and two (2.2%) single IgG3 AMA reactivity. IgG4 AMA was absent. IgG3 titres were higher than IgG2 and IgG1 (P<0.001) and IgG1 higher than IgG2 (P<0.001). IgG3 AMA-positive patients had a histologically more advanced disease (P<0.01) and were more frequently cirrhotic compared with those who were negative (P<0.01). There was a positive correlation between AMA IgG3 titre and Mayo risk score (r=0.55, P=0.009, Spearman's correlation).

Conclusions: Our findings suggest that AMA are not restricted to a specific IgG subclass. AMA of the IgG3 subclass are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

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