The Role ofE. coliInfection in the Pathogenesis of Primary Biliary Cirrhosis

Abstract

Abstract. Among various infectious agents possibly involved in the pathogenesis of primary biliary cirrhosis (PBC), Escherichia Coli (E. coli) has received special attention because of epidemiological and experimental evidence linking this bacterium with the disease's development. This review discusses early and more recent epidemiological studies associating recurrent urinary tract infections with E. coli and the development of PBC. We also critically review data provided over the years demonstrating disease-specific humoral and cellular immune responses against E. coli antigens in patients with PBC. Finally, we assess the relevance of experimental findings reporting cross-reactive immunity between mimicking sequences of E. coli and the major PBC mitochondrial antigens in the pathogenesis of the PBC. We also address the extent to which molecular mimicry and immunological cross-reactivity can be considered as a critical pathogenic process linking infection with self destruction.

A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease

“…UTIs have been associated with other immune-mediated liver diseases such as primary biliary cirrhosis. 27 This is postulated to occur through molecular mimicry between antigens in the microorganism and endogenous host proteins. 27 Future studies should examine the relationship between oestrogen and recurrent UTIs and PSC.…”

Primary Biliary Cirrhosis Associated with Systemic Sclerosis: Diagnostic and Clinical Challenges

“…Additionally, PBC-specific antinuclear autoantibodies (ANAs) can be observed in 30% of patients presenting with multiple nuclear dot (antibodies against Sp100) or nuclear membrane staining patterns (antibodies against gp210) [9, 10, 12, 14, 20], which are preferentially identified using HEp-2 cells as substrate [21]. The autoimmune nature of PBC is supported by a plethora of experimental and clinical data, such as the presence of autoreactive T cells and serum autoantibodies in patients with PBC [8, 15, 22–31]. …”

Emerging Issues in the Immunopathogenesis, Diagnosis and Clinical Management of Primary Biliary Cirrhosis Associated with Systemic Sclerosis

“…E. coli has been strongly associated with PBC (Bogdanos et al, 2010;Burroughs et al, 1984), largely due to the high occurrence of recurrent urinary tract infections in women with PBC (Corpechot et al, 2010;Gershwin et al, 2005). Experimental data support the presence of cross-reactive immune responses between human and E. coli PDC-E2 at the CD4 and CD8 T-cell level (Shigematsu et al, 2000;Van de Water et al, 2001).…”

“…The multiple nuclear dot pattern specific for PBC needs not to be confused with the nuclear dot pattern of anticentromere a n t ib o d i e s ( ACA ) . T h e au to im mun e pa th og en e s i s o f P BC i s s up p or t ed b y a p l e th or a o f experimental and clinical data, such as the presence of autoreactive T cells in PBC patients, and serum autoantibodies characteristic of the disease (Bogdanos et al, 2003;Bogdanos et al, 2010;Bogdanos & Vergani, 2009;Shimoda et al, 1995). The aetiology of PBC is unknown, however the current view is that both genetic susceptibility, and environmental factors are involved together, although these need further characterization.…”

“…The aetiology of PBC is unknown, however the current view is that both genetic susceptibility, and environmental factors are involved together, although these need further characterization. A number of chemicals and infectious agents have been proposed to induce the disease in genetically predisposed individuals (Bogdanos et al, 2010;Bogdanos & Vergani, 2009;Bogdanos et al, 2004a;Bogdanos et al, 2004b;Gershwin & Mackay, 2008;Smyk et al, 2011;Vergani et al, 2004). The presentation of PBC may include symptoms such as pruritus (the most specific symptom of PBC) and fatigue (the most common non-specific symptom), and/or jaundice .…”