Key Points
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Ectopic lymphoid structures (ELSs) develop in the target organs of a subset of patients with rheumatic autoimmune diseases and recapitulate key cellular and molecular features normally present in secondary lymphoid organs
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ELSs in rheumatic autoimmune diseases can function as germinal centres, favouring B cell selection and plasma cell differentiation
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B cells and plasma cells associated with ELSs in rheumatic autoimmune diseases frequently display an autoreactive phenotype towards disease-specific autoantigens
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Ectopic germinal centres in patients with Sjögren syndrome have been associated with more severe systemic manifestations and a higher risk of B cell lymphoma
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In rheumatoid arthritis, emerging but as-yet-inconclusive evidence suggests a role for ELSs in influencing disease evolution and the response to conventional and biologic treatments
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Several candidate therapeutic agents that target ELS-associated pathways are currently in clinical trials for rheumatic autoimmune diseases
Abstract
Ectopic lymphoid neogenesis often occurs in the target tissues of patients with chronic rheumatic autoimmune diseases such as rheumatoid arthritis, Sjögren syndrome and other connective tissue disorders, including systemic lupus erythematosus and myositis. However, the mechanisms of ectopic lymphoid-like structure (ELS) formation and function are not entirely understood. For example, it is unclear whether ELSs indicate distinct disease phenotypes or whether they are evolutionary manifestations of chronic inflammation. Also unclear is why ELSs form in some patients but not in others. Nonetheless, 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 synthetic and biologic DMARDs. In this Review, we discuss current knowledge and gaps in understanding of ELS formation and function including their prevalence in the above rheumatic autoimmune diseases; the mechanisms underlying their formation, maintenance and function, including positive and negative regulatory pathways; their functional relevance in 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 modalities.
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Bombardieri, M., Lewis, M. & Pitzalis, C. Ectopic lymphoid neogenesis in rheumatic autoimmune diseases. Nat Rev Rheumatol 13, 141–154 (2017). https://doi.org/10.1038/nrrheum.2016.217
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DOI: https://doi.org/10.1038/nrrheum.2016.217
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