Primary biliary cirrhosis and Sjögren's syndrome: autoimmune epithelitis

Abstract

Primary biliary cirrhosis (PBC) has been often coined a model autoimmune disease based on the homogeneity amongst patients, the frequency and similarity of antimitochondrial antibodies, including the highly directed immune response to pyruvate dehydrogenase (PDC-E2). A significant number of patients with PBC suffer from sicca and amongst these, there are patients who also have classic Sjögren's syndrome. Indeed, both PBC and Sjögren's syndrome are characterized by inflammation of target epithelial elements. Both diseases can be considered on the basis of a number of other related clinical aspects, including proposed unique apoptotic features of the target tissue, the role of secretory IgA, and the frequency with which both diseases overlap with each other. Indeed, PBC may be considered a Sjögren's syndrome of the liver, whereas Sjögren's syndrome can be equally discussed as PBC of the salivary glands. Dissection of the genetic predispositions for both diseases and especially the molecular basis of effector mechanisms, will become critical elements in developing new therapies.

Figure 1

The worlwide map of PBC and SS geoepidemiology [–79, 126]. Prevalence rate (per million) are illustrated for major areas.

Figure 2

A parallel comparison of the proposed immunopathogenesis of PBC and SS. In both conditions, environmental triggers (putatively infectious agents and xenobiotics) cause salivary or biliary epithelial cell apoptosis and contribute to tolerance breakdown to self antigens exposed on the apoptotic blebs (SSA and SSB) and not protected by post-translational modification (PDC-E2). Salivary and biliary epithelial cells concur to the autoimmune process also by expressing cytokines, HLA class II and adhesion molecules.