1932

Abstract

Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development. Activation of both innate and adaptive immune pathways contributes to disease pathogenesis, with prominent interferon (IFN) signatures identified in both peripheral blood and affected salivary gland tissues. Recently, LINE-1 genomic repeat elements have been proposed as potential triggers of type I IFN pathway activation in SS through activation of Toll-like receptor–dependent and –independent pathways. In view of the increasingly appreciated variability of SS, elucidation of distinct operating pathways in relation to diverse clinical phenotypes and selection of the optimal therapeutic intervention remain major challenges. Inhibition of cathepsin S molecules, blockade of costimulation through administration of abatacept and inhibitors of B7-related molecules and CD40, blockade of B cell function and B cell survival factors, and disruption of the formation of ectopic germinal centers are considered the main therapeutic targets. Well-controlled multicenter clinical trials are ongoing and data are awaited.

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2017-01-14
2024-04-15
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