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World J Hepatol. Jan 27, 2011; 3(1): 1-7
Published online Jan 27, 2011. doi: 10.4254/wjh.v3.i1.1
Genetic susceptibility to autoimmune liver disease
Jochen Mattner
Jochen Mattner, Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen D91054, Germany
Jochen Mattner, Division of Immunobiology, Cincinnati Children’s Hospital, Cincinnati, OH 45229, United States
Author contributions: Jochen Mattner solely wrote the article.
Supported by a Grant from the Deutsche Forschungsgemeinschaft (MA 2621/2-1), the Lupus Research Institute and by Award Number R01DK084054 from the National Institute of Diabetes and Digestive and Kidney Diseases
Correspondence to: Jochen Mattner, MD, Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen D91054, Germany. jochen.mattner@uk-erlangen.de
Telephone: +49-9131-8523640 Fax: +49-9131-8522573
Received: September 13, 2010
Revised: December 12, 2010
Accepted: December 19, 2010
Published online: January 27, 2011

Autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) are considered as putative autoimmune diseases of the liver. Whereas strong evidence that bacterial infection may trigger PBC exists, the etiologies for PSC and AIH remain unknown. Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases, their associations with environmental triggers and the subsequent implications have been difficult to elucidate. While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4) have been suggested as genetic susceptibility factors for all three disorders, we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC, where Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, has recently been specifically associated with the pathogenesis of this devastating liver disease. Ultimately, the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers, establish infection and damage respective target organs.

Keywords: Primary biliary cirrhosis, Novosphingobium, Natural killer T cells, Cytotoxic T lymphocyte antigen 4, Diabetes, Susceptibility loci, Non-obese diabetic congenic mice