Smyk D, Rigopoulou EI, Zen Y, Abeles RD, Billinis C, Pares A, Bogdanos DP. Role for mycobacterial infection in pathogenesis of primary biliary cirrhosis? World J Gastroenterol 2012; 18(35): 4855-4865 [PMID: 23002357 DOI: 10.3748/wjg.v18.i35.4855]
Corresponding Author of This Article
Dimitrios P Bogdanos, MD, PhD, Institute of Liver Studies and Liver Unit, King’s College London School of Medicine at King’s College Hospital and Kings College Hospital NHS Trust Foundation Trust, Denmark Hill Campus, SE5 9RS London, United Kingdom. dimitrios.bogdanos@kcl.ac.uk
Article-Type of This Article
Review
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World J Gastroenterol. Sep 21, 2012; 18(35): 4855-4865 Published online Sep 21, 2012. doi: 10.3748/wjg.v18.i35.4855
Role for mycobacterial infection in pathogenesis of primary biliary cirrhosis?
Daniel Smyk, Eirini I Rigopoulou, Yoh Zen, Robin Daniel Abeles, Charalambos Billinis, Albert Pares, Dimitrios P Bogdanos
Daniel Smyk, Yoh Zen, Robin Daniel Abeles, Dimitrios P Bogdanos, Institute of Liver Studies and Liver Unit, King’s College London School of Medicine at King’s College Hospital and Kings College Hospital NHS Trust Foundation Trust, London SE5 9RS, United Kingdom
Eirini I Rigopoulou, Dimitrios P Bogdanos, Department of Medicine, University Hospital of Larissa, University of Thessaly Medical School, Biopolis, Larissa 41110, Greece
Eirini I Rigopoulou, Institute of Biomedical Research and Technology (BIOMED), CERETETH, Larissa 41222, Greece
Charalambos Billinis, Faculty of Veterinary Medicine, University of Thessaly, Karditsa 43100, Greece
Albert Pares, Liver Unit, Digestive Diseases Institute, Hospital Clínic, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona 08036, Spain
Author contributions: Bogdanos DP and Rigopoulou EI conceived the idea for writing a review on this topic; Smyk D wrote the first draft of the manuscript; Smyk D and Bogdanos DP wrote the subsequent drafts of the manuscripts, although all authors contributed; Zen Y prepared and provided the histological pictures; all authors were responsible for reviewing the manuscript; all authors have read and approved the final manuscript.
Correspondence to: Dimitrios P Bogdanos, MD, PhD, Institute of Liver Studies and Liver Unit, King’s College London School of Medicine at King’s College Hospital and Kings College Hospital NHS Trust Foundation Trust, Denmark Hill Campus, SE5 9RS London, United Kingdom. dimitrios.bogdanos@kcl.ac.uk
Telephone: +44-20-32993397 Fax: +44-20-32993397
Received: June 18, 2011 Revised: April 16, 2012 Accepted: May 6, 2012 Published online: September 21, 2012
Abstract
Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterized by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterized by circulating antimitochondrial antibodies (AMAs) as well as disease-specific antinuclear antibodies, cholestatic liver function tests, and characteristic histological features, including granulomas. A variety of organisms are involved in granuloma formation, of which mycobacteria are the most commonly associated. This has led to the hypothesis that mycobacteria may be involved in the pathogenesis of PBC, along with other infectious agents. Additionally, AMAs are found in a subgroup of patients with mycobacterial infections, such as leprosy and pulmonary tuberculosis. Antibodies against species-specific mycobacterial proteins have been reported in patients with PBC, but it is not clear whether these antibodies are specific for the disease. In addition, data in support of the involvement of the role of molecular mimicry between mycobacterial and human mitochondrial antigens as triggers of cross-reactive immune responses leading to the loss of immunological tolerance, and the induction of pathological features have been published. Thus, antibodies against mycobacterial heat shock protein appear to cross-recognize AMA-specific autoantigens, but it is not clear whether these autoantibodies are mycobacterium-species-specific, and whether they are pathogenic or incidental. The view that mycobacteria are infectious triggers of PBC is intriguing, but the data provided so far are not conclusive.
