Abstract
Primary biliary cirrhosis (PBC)is a chronic autoimmune cholestatic liver disease that manifests a latitudinal gradient in prevalence and incidence. The mechanisms leading to the initiation and perpetuation of PBC remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. PBC is also characterized by a high concordance rate in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. From a diagnostic standpoint, PBC is characterized by the highest specificity of serum autoantibodies directed at mitochondrial proteins. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics that will be critically discussed in the present review article.
Highlights
Primary biliary cirrhosis (PBC) is a rare organspecific autoimmune disease characterized by an immune-mediated destruction of small- and mediumsize bile ducts with resulting chronic cholestasis and liver cirrhosis [1]
One major paradox in PBC pathogenesis is common to several autoimmune diseases and is based on the observation that, the autoimmune attack is directed against ubiquitous mitochondrial antigens belonging to the family of 2oxoacid dehydrogenase complexes (2-OADC), the disease involves biliary epithelial cells, i.e. cholangiocytes [2]
As for other autoimmune diseases, genetic and environmental factors are involved in PBC pathogenesis, as well represented in monozygotic twins who fail to demonstrate a complete concordance rate [4] or the reported significant genetic associations encountered in subgroups of
Summary
Primary biliary cirrhosis (PBC) is a rare organspecific autoimmune disease characterized by an immune-mediated destruction of small- and mediumsize bile ducts with resulting chronic cholestasis and liver cirrhosis [1]. One major paradox in PBC pathogenesis is common to several autoimmune diseases and is based on the observation that, the autoimmune attack is directed against ubiquitous mitochondrial antigens belonging to the family of 2oxoacid dehydrogenase complexes (2-OADC), the disease involves biliary epithelial cells, i.e. cholangiocytes [2]. Liver infiltrating autoreactive T cells are found in patients with PBC irrespective of their AMA status [9] These cells recognize antigens overlapping with AMA specificities and are thought to play the major role in biliary cell destruction through direct cytotoxicity (CD8+ cells) and as a result of cytokine production (CD4+) [7,10], as well established in liver immunity [11,12]
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