Autoantibodies and autoantigens in Sjögren’s syndrome

Autoantibodies are a key serological feature of Sjögren’s syndrome (SS). The presence of Ro/Sjögren’s syndrome-related antigen A (SSA) autoantibodies is one of the items with the highest weight in the 2016 joint ACR/EULAR SS classification criteria. Autoantibodies appear before overt clinical disease manifestations, and patient autoantibody profiles seem stable over time, even after B-cell depleting therapy. Expression of Ro/SSA and La/Sjögren’s syndrome-related antigen B (SSB), the major autoantigens in SS, in the target organs (exocrine glands), local autoantibody production, and the capacity of autoantigen-containing immune complexes to induce interferon production all point to a central involvement of autoantibodies in disease pathogenesis. Here, we review the main autoantibody specificities reported in SS, their clinical associations, the current understanding of how autoantibody production is initiated and maintained, and how autoantibodies may exert pathogenic effects. We provide a comprehensive overview of the nature and biological function of the three main autoantigens, Ro52, Ro60, and La (Ro/SSA and La/SSB) found in SS.