Detection of M2 antibodies in patients with recurrent urinary tract infection using an ELISA and purified PBC specific antigens. Evidence for a molecular mimicry mechanism in the pathogenesis of primary biliary cirrhosis?

Abstract

Primary Biliary Cirrhosis (PBC) is a chronic liver disease of unknown aetiology. The main characteristic feature of the disease is the presence of circulating antimitochondrial antibodies (AMA) to components (collectively named M2) of the mitochondrial 2-oxo-acid multienzyme complexes; pyruvate, oxoglutarate and branched chain oxo-acid dehydrogenase complexes. As these enzymes are phylogenetically conserved, AMA also exhibit reactivity against a range of microorganisms. PBC patients have an increased incidence of recurrent urinary tract infection (UTI) compared to other chronic liver disease controls. Interestingly, we have recently detected low titre AMA in patients with a history of recurrent UTI but normal liver function using crude bovine heart mitochondrial preparations and immunoblotting techniques. Here we confirm these findings using purified M2 antigens and ELISA. We found that 52% of "normal" subjects with a history of recurrent UTI had AMA specifically to M2 antigens. The percentage was significantly higher than that found for chronic liver disease (19%, p < 0.01) and normal controls (4%, p < 0.001). These results support our hypothesis for molecular mimicry in PBC. We propose that a bacterial trigger, possibly resulting from recurrent UTIs, is responsible for initiating an autoimmune response in a predisposed host because of a cross-reactivity between mitochondrial and bacterial antigens.