Environmental factors and the induction of autoimmunity in primary biliary cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease with an autoimmune pathogenesis and an unknown etiology, predominantly affecting postmenopausal women. The term PBC is a misnomer since most cases currently diagnosed have limited probability to develop cirrhosis. Antimitochondrial autoantibodies, elevated IgM and selective destruction of the intrahepatic bile ducts are the hallmarks of PBC. A permissive genetic background is critical in producing susceptibility despite limited associations with alleles within the MHC. The disease has incomplete concordance in monozygotic twins and its geoepidemiology suggests a role for environmental factors in the induction of PBC. This hypothesis is further supported by clinical (risk factors) and experimental evidence. Some of the factors incriminated model molecular mimicry by infectious agents and xenobiotic chemicals. Additional candidates are being proposed through large screening; all proposed associations ultimately require confirmation in animal models and clinical practice.

Keywords::

• autoimmune cholangitis
• geoepidemiology
• molecular mimicry
• nonynoic acid
• Novosphingobium spp.
• pyruvate dehydogenase
• serum autoantibody
• xenobiotic

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.