• anti-m3AChR autoantibodies;
  • anti-PDC-E2 autoantibodies;
  • apoptosis;
  • autophagy;
  • Bcl-2 family;
  • danger signals;
  • innate autoimmunity;
  • neuro-endocrine receptors;
  • primary biliary cirrhosis;
  • scleroderma;
  • Sjoegren disease


The aetiology of primary biliary cirrhosis (PBC) remains unknown. Infectious and non-infectious noxious insults in combination with tissue-specific factors may precipitate PBC. Activation of innate immune response because of impending danger signals seems to be a key event in early PBC, as evidenced by granuloma formation, eosinophilic reaction and IgM elevation. Aberrant mitophagy in ‘stressed’ biliary epithelia cells may initiate the immune response against mitochondrial antigens. Antimitochondrial autoantibodies recognize evolutionarily conserved molecules. The question arises, whether they are pathogenic or rather an expression of beneficial autoimmunity. The generally stable course of PBC suggests that stimulatory and inhibitory autoimmune reactions govern the inflammatory biliary process. Tissue repair and defense are the heart of innate immunity. But continuous exposure of exogenous stimuli may precipitate functional antireceptor autoantibodies that are no more protective but rather harmful. Mitophagy, apoptosis and bile duct proliferation define the inflammatory response within bile ducts. Autoantigens may be clustered in different blebs on the surface of apoptotic cells targeting a variety of membrane and non-membrane-associated antigens. Thus, the autoantibody response in PBC may target, for instance, the pro- and anti-apoptotic proteins of the Bcl-2 family or receptors of the adrenergic or cholinergic system, hereby interfering with the programme of apoptosis and the proliferation of biliary epithelial cells. Consideration of there being functional autoantibodies into the pathogenesis of PBC may help to improve our understanding of the aetiopathogenesis of PBC.