Objective

Ectopic lymphoid structures (ELSs) characterised by B/T cell aggregates and networks of follicular dendritic cell often develop in the target tissues of patients with chronic rheumatic autoimmune diseases such as the synovial tissue in rheumatoid arthritis (RA) and the salivary glands in Sjögren syndrome (SS). ELSs frequently display functional features of ectopic germinal centres and can actively contribute to the maintenance of autoimmunity through the production of disease-specific autoantibodies; furthermore, they seem to influence disease severity and response to both traditional and biologic DMARDs. In the context of this talk, I will discuss current knowledge and gaps in understanding of ELS formation and function; the mechanisms underlying their formation, maintenance and function, including positive (i.e. lymphoid chemokines, lymphotoxins and specific Th cell subsets such as T follicular helper cells ) and negative (i.e. IL-27) regulatory pathways; their functional relevance in the local differentiation of disease-specific autoreactive B cells and the perpetuation of autoimmunity; their relationship with disease phenotypes, clinical outcomes and response to treatment; and the potential for specific targeting of ELSs through novel therapeutic strategies.