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.