Pathogenesis of Sjogren’s Disease

In this segment, the discussion focuses on the current understanding of the pathogenesis of Sjögren’s Disease (SjD). The panel explains that while SjD is not driven by a single gene, genetic susceptibility contributes to an exaggerated inflammatory response. The disease is thought to begin with an initial insult to the salivary glands—often conceptualized as environmental or viral exposures—which damages epithelial cells. These cells then release pro-inflammatory signals, including BAFF and other cytokines, that recruit innate immune cells and subsequently B and T lymphocytes. Over time, these immune interactions form germinal center–like structures within the glands, leading to autoantibody production, persistent glandular inflammation, and reduced tear and saliva secretion. The same inflammatory processes can extend beyond the glands, driving systemic involvement. This chronic B-cell–driven immune activation also underlies SjD’s increased risk of lymphoma, highlighting the need for therapies that interrupt this cycle.