Primary Sjögren Syndrome: Etiology and Pathogenesis

Primary Sjögren syndrome is a chronic inflammatory disorder of the lacrimal and salivary glands resulting in oral and ocular dryness. It also has extraglandular manifestations that may affect the lung, kidneys, nervous system, and other organs. The etiology and pathogenesis of primary Sjögren syndrome are incompletely understood. A working hypothesis considers the disease to be driven by a complex interplay of environmental, genetic, and epigenetic factors. Recent genome-wide association studies confirm the previously shown contribution of major histocompatibility (MHC) locus to disease susceptibility and illuminate several non-MHC loci, which add to disease risk. New gene expression studies of peripheral blood and salivary gland tissue provide further molecular detail about the role of innate and adaptive immune pathways involved in disease mechanisms. In particular, upregulated expression of interferon and B cell–activating factor appear to play key roles in this process. Despite their drawbacks, experimental animal models continue to stimulate new lines of research that are advancing our understanding of human disease. This knowledge has been translated into new therapeutic approaches currently under evaluation in clinical trials. This review contains 5 figures, 2 tables, and 67 references. Key words: adaptive immunity, animal models, epigenetics, genome-wide association studies, innate immunity, interferon signature, lymphoma pathogenesis, nucleic acid sensing, primary Sjögren syndrome