Autoimmunity and environmental factors in the pathogenesis of primary biliary cirrhosis.
It is generally believed that autoimmune processes are initiated when tolerance to self-proteins is broken. Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Autoimmune attack in PBC is predominantly organ-specific, despite the presence of mitochondrial autoantigens, the major targets of autoimmunity in PBC, in all nucleated cells. Although the events that provoke initial activation remain unknown, the hypothesis of molecular mimicry implies that foreign pathogens with homology to self-protein or modified self-protein can break tolerance. Several reports have suggested the association of autoimmune diseases with drugs, chemicals, and other environmental factors. Specifically, many xenobiotics are metabolized in the liver. Liver autoantigens exposed to these chemicals could be modified and become immunogenic. We propose that exposure to the environmental xenobiotics is one of the initiating factors that leads to the loss of tolerance to self-proteins in genetically susceptible hosts, resulting in development of PBC.
Kita
Hiroto
H
Department of Gastroenterology, Jichi Medical School, Yakushiji, Kawachi, Tochigi, 329-0438, Japan.
He
Xiao-Song
XS
Gershwin
M Eric
ME
D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000187:drug effects / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000276:immunology*; D018716:Molecular Mimicry / Q000276:immunology; D015262:Xenobiotics / Q000633:toxicity*
D001323:Autoantibodies; D001324:Autoantigens; D015262:Xenobiotics