Purpose of review: The purpose of this review is to provide an insight into the pathophysiological mechanisms involved in the pathogenesis of primary Sjögren's Syndrome (pSS), highlighting recent findings with potential therapeutic repercussions.
Recent findings: In the last 2 years, epigenetic analyses provided new insights into pSS pathogenesis. Characterization of DNA methylation patterns, chromatin structures and microRNA confirmed the importance of aberrant interferon and B-cell responses in the development of the disease. The formation of ectopic B-cell follicles with germinal centers is now a well recognized pathogenic mechanism within salivary glands of pSS. In the context of ectopic germinal centers reaction, T/B-cell interactions, that is regarding T-helper 17 and T-follicular helper cells, and their respective counterparts, T-regulatory and T-follicular regulatory cells, appear particularly relevant in pSS pathogenesis as their imbalance is associated with a dysregulation of B-cell dynamics and the production of autoantibodies.
Summary: Advances in the understanding of pSS pathogenesis have paved the way for clinical trials with novel biologic agents targeting immune pathways regulating T/B-cell interactions and downstream B-cell activation. Reverse translation from these studies provides invaluable novel information of the mechanisms sustaining autoimmunity and chronic inflammation in pSS.