scholarly journals Infectious Agents in the Pathogenesis of Primary Biliary Cirrhosis

2010 ◽  
Vol 29 (6) ◽  
pp. 277-286 ◽  
Author(s):  
Oscar-Danilo Ortega-Hernandez ◽  
Nancy-Agmon Levin ◽  
Arie Altman ◽  
Yehuda Shoenfeld
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Pyruvate Dehydrogenase ◽  
Molecular Mimicry ◽  
Pyruvate Dehydrogenase Complex ◽  
Amino Acid Sequences ◽  
Molecular Evidence ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Infectious Agents ◽  
Autoimmune Process

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease which is characterized by the breakdown of self-tolerance to the highly conserved pyruvate dehydrogenase complex, specially the pyruvate dehydrogenase E2 complex (PDC-E2). The breakdown of the tolerance to such antigens leads to an autoimmune process characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Epidemiological studies have suggested that infections agents can trigger or even exacerbate the disease. Among other gram negative bacteria,Escherichia Coli, andNosphingobium aromaticivoransare the most associated agents reported hitherto. Epidemiological and molecular evidence points towards molecular mimicry between some components of these microorganisms and specific amino-acid sequences that are present in proteins on normal cells of the biliary tract. In this review, we revisit all reports suggesting that infectious agents might be associated with the autoimmune pathogenesis of PBC. We also retrieve the immune molecular mimicry mechanisms that are likely involved with the autoimmune process in PBC.

scholarly journals Oral Tolerance and Pyruvate Dehydrogenase in Patients with Primary Biliary Cirrhosis

2002 ◽  
Vol 9 (2) ◽  
pp. 55-61 ◽  
Author(s):  
Ayako Suzuki ◽  
Judy van de Water ◽  
M. Eric Gershwin ◽  
Roberta Jorgensen ◽  
Paul Angulo ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Pyruvate Dehydrogenase ◽  
Oral Tolerance ◽  
Early Stage ◽  
Pyruvate Dehydrogenase Complex ◽  
Tolerance Induction ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Antimitochondrial Antibodies ◽  
Immunological Destruction

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity.

scholarly journals Infection as a Risk Factor in the Pathogenesis of Primary Biliary Cirrhosis: Pros and Cons

2010 ◽  
Vol 29 (6) ◽  
pp. 313-321 ◽  
Author(s):  
Teru Kumagi ◽  
Masanori Abe ◽  
Yoshiou Ikeda ◽  
Yoichi Hiasa
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Environmental Factors ◽  
Molecular Mimicry ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Infectious Agents ◽  
Case Control Studies ◽  
Intrahepatic Bile Ducts ◽  
Genome Wide ◽  
Pros And Cons

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intrahepatic bile ducts that may eventually lead to cirrhosis and liver failure. Evidence suggests cardinal roles for both environmental factors and genetic susceptibility. Nevertheless, the absolute etiology of PBC is unclear, despite recent well-designed case-control studies that reported environmental risk factors, including infectious agents, for PBC. Of the reported infectious agents, some of them are not reproducible and remain controversial. However, infection is no doubt one of the major risks among the environmental factors. This is supported by the fact that infectious agents in autoimmune diseases express antigens resulting in molecular mimicry and xenobiotics that play a role in breaking tolerance. Taken together, recent findings from genome wide assays as well as novel animal models may enable us to better understand the mechanism of pathogenesis responsible for this disease.

Sign in / Sign up

Export Citation Format

Share Document