The Chemical Pathway to Primary Biliary Cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a female predominant chronic disease of autoimmune pathogenesis and unknown etiology, although data suggest that genetic predisposition and environmental factors concur to its onset. Among nongenetic factors, several lines of evidence spanning from geoepidemiology to experimental findings support the role of xenobiotics, i.e., chemicals that are capable to induce molecular mimicry through cross reactivity. Indeed, specific xenobiotics are hypothesized to substitute lipoic acid residues on PBC-specific autoepitopes thus triggering autoimmunity. This is supported by data obtained with patient sera reactivities as well as animal models. The scenario is further complicated by the possibility that xenobiotic-metabolizing bacteria might also play a role. We will review the available evidence in this intriguing and rapidly growing field of research and critically discuss its potential implications.

Role of the Anion Exchanger 2 in the Pathogenesis and Treatment of Primary Biliary Cirrhosis

“…Several studies, some of which are controversial, suggest that bacteria like Novosphingobium aromaticivorans [42], viruses such as a betaretrovirus [43,44], or xenobiotics in cosmetics (e.g. the 2-nonynoic acid and food additive 2-octynoic acid) [45] may trigger the distinctive self-tolerance breakdown in susceptible individuals. However, the mechanisms of breakdown of B cell and T cell self-tolerance to PBC autoantigens in such a cell-specific manner remain unclear.…”

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

“…However, it is well documented in the literature that sera from patients with different AID cross-reacts with xenobiotics (Selmi et al 2009) and pathogens, including virus, bacteria and parasites (Capron et al 1965, Dissous et al 1986, DanielRibeiro & Zanini 2000, Gregorio et al 2003, Amano et al 2005, Blank et al 2007, Bogdanos & Vergani 2009. �his cross-reactivity is the basis for the "molecular mimicry" hypothesis, originally formulated by Damian (1964), who suggested that antigenic determinants of micro-organisms may resemble antigenic determinants of their host.…”

What Is New in Primary Biliary Cirrhosis?

“…Xenobiotics have been implicated previously in the pathogenesis of several autoimmune diseases, including PBC [26,27]. Xenobiotics are capable of altering self-peptides, in addition to mimicking several sequences, in a fashion similar to molecular mimicry.…”