Table 2

PBC risk factors associated with female sex and ageing

Female Risk Factor

Significance

Recurrent urinary tract infections

Molecular mimicry and cross reactivity with bacterial (such as E. coli) peptides and PDC-E2 epitopes

Oestrogen deficiency

Increased propensity towards ductopaenia

Increased incidence of vaginal infections

Alterations in vaginal flora increase the risk of developing urinary tract infections, which appear to play a role in PBC

Ageing Risk Factors

Significance

T cell membrane rigidity and decreased cell membrane fluidity

Alterations in T cell receptor signalling

Decreased CD28 expression (especially in CD8+ cells)

Reduced regulatory T cell function and reduced immune response to infections

Phenotypical alterations in CD8+ cells (such as increased CD127, and decreased CD39)

Decreased T regulatory cell function

Increased telomere shortening from oxidative stress an ongoing inflammation

Increased cellular senescence, autophagy and apoptosis

Increased senescence and autophagy

May contribute to exposure of self antigens to the immune system, as well as contributing to a pro-fibrotic and pro-inflammatory environment

Increased apoptosis

Formation of apoptotic blebs (apotopes) increase exposure of mitochondrial antigens to the immune system

Several risk factors related to female sex and increased age appear to be significant in the pathogenesis of primary biliary cirrhosis (PBC). Risks associated with females include recurrent urinary tract infections, oestrogen deficiency, and increased incidence of vaginal infections. Age related changes (which may increase risk for PBC development) include alterations in regulatory T cell function, increased senescence and autophagy, as well as apoptosis.

Smyk et al. Immunity & Ageing 2011 8:12   doi:10.1186/1742-4933-8-12