Primary biliary cirrhosis and autoimmunity: Evaluating the genetic risk

The genetic basis of autoimmunity is receiving increased attention. Organ-s pecific diseases, such as primary biliary cirrhosis, may be considered mode l diseases to use for development of databases and extrapolation to other a utoimmune diseases. PBC is an enigmatic autoimmune disease that predominant ly affects females and leads to destruction of intrahepatic bile ducts. The serologic hallmark of this disease is anti-mitochondrial antibodies that s pecifically react with the E2 components of 2-oxodehydrogenase enzymes, inc luding PDC-E2. There are no clear major histocompatibility complex associat ions with the development of PBC, despite the observation that first-degree relatives of index patients with PBC have a 4-6% prevalence of development of PBC. This risk factor is comparable or higher than any other human auto immune disease and suggests that a genome-wide approach towards dissection of genetic associations would lead to valuable new insights. In this review we place these concepts in perspective and highlight in particular the gen etic associations in primary biliary cirrhosis.