Chronic Autoimmune Epithelitis in Sjögren's Syndrome and Primary Biliary Cholangitis: A Comprehensive Review

Within the spectrum of autoimmune diseases, Sjögren's syndrome and primary biliary cholangitis are exemplary and can be coined as chronic epithelitis based on their frequent coexistence in clinical practice and the highly specific immune-mediated injury of the small bile ducts and the exocrine glands. The pathogenic mechanisms underlying the diseases are similar, with apoptosis being the key element leading to organ-specific immune-mediated injury directed against the small bile ducts and salivary gland epithelia, respectively along with similar epidemiological features, such as female predominance and the age of onset in the fifth decade of life. Indeed, novel insights into the pathogenesis of the diseases have been obtained in recent years, including a better definition of the role of B and T cells, particularly Th17 cells, and the mechanisms of autoantibody-mediated tissue injury, with anti-mitochondrial antibodies and SS-A/SS-B being identified as specific for primary biliary cholangitis and Sjögren's syndrome, respectively. These findings have opened the possibility to new targeted therapies, but most clinical needs remain unmet, particularly from a therapeutic standpoint where options diverge, with bile acids being the predominant treatment strategy in primary biliary cholangitis and immunomodulators being used to treat Sjögren's syndrome. Here we provide a comprehensive review of the most recent findings on the pathogenesis, clinical manifestations and therapeutic options for Sjögren's syndrome and primary biliary cholangitis, respectively, while stressing the common traits between these conditions. Our cumulative hypothesis is that similarities outnumber differences and that this may prove advantageous towards a better management of patients.