Primary biliary cirrhosis (PBC), a classic autoimmune liver disease, is characterised by a progressive T cell predominant lymphocytic cholangitis, and a serologic pattern of reactivity in the form of specific anti-mitochondrial antibodies (AMA). CD4+ T cells are particularly implicated by PBC's cytokine signature, the presence of CD4+ T cells specific to mitochondrial auto-antigens, the expression of MHC II on injured biliary epithelial cells, and PBC's coincidence with other similar T cell mediated autoimmune conditions. CD4+ T cells are also central to current animal models of PBC, and their transfer typically also transfers disease. The importance of genetic risk to developing PBC is evidenced by a much higher concordance rate in monozygotic than dizygotic twins, increased AMA rates in asymptomatic relatives, and disproportionate rates of disease in siblings of PBC patients, PBC family members and certain genetically defined populations.

It is characterised by the progressive loss of small intrahepatic bile ducts with resultant cholestasis and progressive fibrosis. One in 1000 women over the age of 40 liver have PBC, and there remains only one licensed therapy – ursodeoxycholic acid. Failure to respond to this treatment puts patients at risk of progressive ductopenia and fibrosis, which ultimately requires liver transplantation to avoid death from liver failure. Current disease models envisage an immune-driven biliary injury, resulting in secondary cholestasis, and which arises on the background of combined genetic and environmental risks. Further mechanistic insights should illuminate better therapeutic options for patients. Herein we consider the immunogenetic basis for PBC and the potential for this new knowledge to translate into improved disease management.

Regards

John
Editorial Assistant
Immunogenetics Open Access