Influence of genes, sex, age and environment on the onset of autoimmune hepatitis.
The pathogenesis of autoimmune hepatitis (AIH) is complex. However, it is believed that a susceptible individual, owing to his genetic background, sex and age, can develop the disease following exposure to an environmental trigger. Autoimmune hepatitis does not follow a Mendelian pattern of inheritance; hence no single causative genetic locus has been identified. However, several genes, inside and outside the HLA locus, have been linked to an increased susceptibility to AIH. Epidemiological evidence also suggests that the sex and age of the patient plays a role in AIH pathogenesis as the disease onset occurs mainly in the two first decades of life and a higher disease incidence is observed in females. No environmental trigger has been identified, but several have been proposed, mainly viruses and xenobiotics. This article aims at reviewing the current knowledge on susceptibility factors leading to AIH and putative triggers, emphasizing fundamental mechanisms responsible for the break of liver immunological tolerance.
Béland
Kathie
K
Lapierre
Pascal
P
Alvarez
Fernando
F
D017668:Age of Onset; D015551:Autoimmunity; D004777:Environment; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008297:Male; D018716:Molecular Mimicry; D012744:Sex Ratio; D013601:T-Lymphocytes / Q000276:immunology
D006680:HLA Antigens