Review
Immunopathogenesis of primary biliary cirrhosis: an old wives' tale
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* Corresponding author: Dimitrios P Bogdanos dimitrios.bogdanos@kcl.ac.uk
1 Institute of Liver Studies, King's College London School of Medicine at King's College Hospital and Kings College Hospital NHS Trust Foundation, London, SE5 9RS UK
2 Department of Medicine, University of Thessaly Medical School, Viopolis, 41110, Larissa, Greece
3 Institute of Biomedical Research and Technology (BIOMED), CERETETH, 41222, Larissa, Greece
4 Center for Autoimmune Liver Diseases, Division of Internal Medicine, IRCCS Istituto Clinico Humanitas, Rozzano 20089, Italy
5 Department of Translational Medicine, Università degli Studi di Milano, Rozzano, Italy
6 Faculty of Veterinary Medicine, University of Thessaly, Karditsa, Greece
7 Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA
Immunity & Ageing 2011, 8:12 doi:10.1186/1742-4933-8-12
Published: 2 December 2011Abstract
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the autoimmune destruction of the small intrahepatic bile ducts. The disease has an unpredictable clinical course, but may progress to fibrosis and cirrhosis. Although medical treatment with urseodeoxycholic acid is largely successful, some patients may progress to liver failure requiring liver transplantation. PBC is characterised by the presence of disease specific anti-mitochondrial (AMA) antibodies, which are pathognomonic for PBC development. The disease demonstrates an overwhelming female preponderance and virtually all women with PBC present in middle age. The reasons for this are unknown; however several environmental and immunological factors may be involved. As the immune systems ages, it become less self tolerant, and mounts a weaker response to pathogens, possibly leading to cross reactivity or molecular mimicry. Some individuals display immunological changes which encourage the development of autoimmune disease. Risk factors implicated in PBC include recurrent urinary tract infection in females, as well as an increased prevalence of reproductive complications. These risk factors may work in concert with and possibly even accelerate, immune system ageing, contributing to PBC development. This review will examine the changes that occur in the immune system with ageing, paying particular attention to those changes which contribute to the development of autoimmune disease with increasing age. The review also discusses risk factors which may account for the increased female predominance of PBC, such as recurrent UTI and oestrogens.