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Editor—Primary biliary cirrhosis (PBC) is a chronic, slowly progressive cholestatic liver disease believed to result from autoimmune mechanisms. The initiation of the disease is likely to be multifactorial with genetic, infectious, and environmental factors contributing. A familial predisposition to PBC has been reported, but studies to investigate an association between PBC and polymorphisms at a number of genetic loci have not been conclusive. The aetiology of the disease remains unknown but it has been suggested that R forms of E coli 1 andMycobacterium gordonae 2 3 may play a potentially pathogenic role in PBC, though this has not been established. A common characteristic feature of PBC is the presence of granulomas and it is interesting to note that these tend to disappear as the lesions progress and fibrosis and cholestasis appear, that is, secondary effects of tissue damage.
NRAMP1 (natural resistance associated macrophage protein 1) was isolated as the human homologue of the mousenramp1 gene (previously designatedIty/Lsh/Bcg) which, when mutated, is responsible for susceptibility to a number of macrophage trophic intracellular pathogens including Mycobacterium bovis, Salmonella typhimurium, andLeishmania donovani.4Expression of the gene is restricted to cells of the mononuclear phagocytic system (macrophages and granulocytes)5 and it plays an important role in the activation of macrophages and innate immunity. When nramp1 is mutated, mice fail to control pathogen growth in the early stages of infection. Sequence analysis of nramp1 and recent functional studies suggest that the gene encodes a multispanning transmembrane transporter protein6 with specificity for divalent metal cations,7 but its physiological role in relation to macrophage function is …