Genetic susceptibility to autoimmune liver disease

World J Hepatol. 2011 Jan 27;3(1):1-7.

Genetic susceptibility to autoimmune liver disease.
Mattner J.

Jochen Mattner, Microbiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen D91054, Germany.

Abstract

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.

PMID: 21307981 [PubMed - in process]PMCID: PMC3035697
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Figure 1Regulation of T cell activation by cytotoxic T lymphocyte antigen 4. While cytotoxic T lymphocyte antigen 4 (CTLA-4) is constitutively expressed on regulatory T cells (Tregs), its expression is induced on effector T cells (Teff) upon activation. While it is well-established that CTLA-4 is required f...Genetic susceptibility to autoimmune liver diseaseWorld J Hepatol. 2011 January 27;3(1):1-7.

full-text:
Genetic susceptibility to autoimmune liver disease