Journal
CURRENT OPINION IN RHEUMATOLOGY
Volume 17, Issue 5, Pages 558-565Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.bor.0000172801.56744.c3
Keywords
animal models; immunopathogenesis; predisposing factors; serology; Sjogren's syndrome; therapy
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Funding
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [ZIAAR041127, Z01AR041127] Funding Source: NIH RePORTER
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Purpose of review Recent studies have broadened our understanding of the etiopathogenesis and immunopathology of primary Sjogren's syndrome. This review highlights recent advances in understanding the underlying mechanisms of the disease as well as their implications for clinical handling and therapeutic options. Recent findings It becomes increasingly apparent that certain disturbances of the immune system (i.e. B-cell hyperreactivity and enhanced levels of B-cell-activating factor/B-lymphocyte stimulator) play a central role in this entity. Whether this is a primary abnormality or the result of predisposing factors or infectious, e.g. viral, agents remains uncertain. New insights into the pathogenesis also provide candidates for better diagnosis and classification of disease severity, such as flow cytometric analysis, measurement of soluble cell surface molecules, autoantibodies, cytokines, and ligands (B-cell-activating factor/B-lymphocyte stimulator). Whether B-cell-directed therapies (i.e. blocking B-cell-activating factor/B-lymphocyte stimulator, anti-CD20 therapy) will have an impact on primary Sjogren's syndrome needs to be shown in clinical trials. Alternative therapeutic approaches such as organ-targeted gene transfer are in development but must be carefully evaluated for safety and efficacy in preclinical models that resemble human primary Sjogren's syndrome. Summary The pathogenesis of primary Sjogren's syndrome is complex and the factors initiating and driving autoimmunity in this entity are largely unknown. Recent studies provide new insights into potential pathogenetic mechanisms of the disease and, thereby, the chance for improved strategies in disease management and therapy.
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