Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation to autoimmunity and tissue damage/remodeling

Rheumatoid arthritis is a chronic systemic inflammatory disease primarily affecting the synovium of diarthrodial joints. Despite the currently unknown etiology, overwhelming evidence indicates that both innate and adaptive immunity play a central role in disease pathogenesis. In this review, we consider recent evidence examining the mechanisms of lymphoid tissue reactivity in rheumatoid arthritis with a focus on the dynamics controlling secondary and ectopic lymphoid tissue response. We then examine the cellular and molecular mechanisms regulating the biopathology of these processes with specific emphasis on cell trafficking, contribution to autoimmunity, and joint damage-repair. We finally provide a brief overview of the most recent studies addressing the clinical relevance of synovial lymphoid tissue analysis as a diagnostic and prognostic tool as well as its response to current biological therapies.