Xenobiotics and loss of tolerance in primary biliary cholangitis

Jinjun Wang, Guoxiang Yang, Alana Mari Dubrovsky, Jinjung Choi, Patrick S Leung

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)338-348
Number of pages11
JournalWorld Journal of Gastroenterology
Volume22
Issue number1
DOIs
StatePublished - Jan 7 2016

Keywords

  • Antimitochondrial autoantibodies
  • Breaking of tolerance
  • Primary biliary cholangitis
  • Pyruvate dehydrogenase E2
  • Xenobiotics

ASJC Scopus subject areas

  • Gastroenterology

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