title: Immunopathogenesis of primary biliary cirrhosis: an old wives' tale.
abstract: 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.
authors.affiliation: 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. dimitrios.bogdanos@kcl.ac.uk.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Smyk
authors.forename: Eirini I
authors.initials: EI
authors.lastname: Rigopoulou
authors.forename: Ana
authors.initials: A
authors.lastname: Lleo
authors.forename: Robin D
authors.initials: RD
authors.lastname: Abeles
authors.forename: Athanasios
authors.initials: A
authors.lastname: Mavropoulos
authors.forename: Charalambos
authors.initials: C
authors.lastname: Billinis
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Bogdanos