TY - JOUR
T1 - Xenobiotics and loss of tolerance in primary biliary cholangitis
AU - Wang, Jinjun
AU - Yang, Guoxiang
AU - Dubrovsky, Alana Mari
AU - Choi, Jinjung
AU - Leung, Patrick S
PY - 2016/1/7
Y1 - 2016/1/7
N2 - Data from genome wide association studies and geoepidemiological studies established that a combination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis (PBC). The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies (AMA) that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2 (PDC-E2) subunit. Extensive efforts have been directed to investigate the molecular basis of AMA. Recently, experimental data has pointed to the thesis that the breaking of tolerance to PDC-E2 is a pivotal event in the initial etiology of PBC, including environmental xenobiotics including those commonly found in cosmetics and food additives, suggesting that chemical modification of the PDC-E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts. Here, we will discuss the natural history, genetics and immunobiology of PBC and structural constraints of PDC-E2 in AMA recognition which makes it vulnerable to chemical modification.
AB - Data from genome wide association studies and geoepidemiological studies established that a combination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis (PBC). The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies (AMA) that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2 (PDC-E2) subunit. Extensive efforts have been directed to investigate the molecular basis of AMA. Recently, experimental data has pointed to the thesis that the breaking of tolerance to PDC-E2 is a pivotal event in the initial etiology of PBC, including environmental xenobiotics including those commonly found in cosmetics and food additives, suggesting that chemical modification of the PDC-E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts. Here, we will discuss the natural history, genetics and immunobiology of PBC and structural constraints of PDC-E2 in AMA recognition which makes it vulnerable to chemical modification.
KW - Antimitochondrial autoantibodies
KW - Breaking of tolerance
KW - Primary biliary cholangitis
KW - Pyruvate dehydrogenase E2
KW - Xenobiotics
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U2 - 10.3748/wjg.v22.i1.338
DO - 10.3748/wjg.v22.i1.338
M3 - Article
C2 - 26755880
AN - SCOPUS:84953426371
VL - 22
SP - 338
EP - 348
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 1
ER -