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  • Title: Pathogenesis of Sjögren's syndrome and therapeutic consequences.
    Author: Mariette X, Gottenberg JE.
    Journal: Curr Opin Rheumatol; 2010 Sep; 22(5):471-7. PubMed ID: 20671520.
    Abstract:
    PURPOSE OF REVIEW: To summarize recent findings on new pathogenic mechanisms of interaction between genetic and environmental factors and between innate and adaptive immunity in primary Sjögren's syndrome and to reconcile pathogenesis and treatment by focusing on the crucial pathogenic steps that could be targeted by emerging therapies. RECENT FINDINGS: Regarding genetic predisposition, the functional relevance of IRF5 and STAT4 gene polymorphisms in the activation of type I interferon pathways has been demonstrated. It has also been shown that the isolated stimulation of innate immunity in mice can result in dryness, which precedes lymphocytic infiltrates in salivary glands. In animal models, possible environmental triggers of the disease, such as oestrogen deficiency and/or infection by Epstein-Barr virus, can lead to innate immune followed by autoimmune epithelitis. The IFN-BAFF-B lymphocyte pathogenic axis is, therefore, targeted by numerous drugs currently in evaluation. The development of consensus disease activity scores and patient-related outcomes might help to initiate new controlled trials. The first positive randomized controlled trial with rituximab has been recently published. SUMMARY: Hopefully, persistent and joint efforts by many teams to improve the knowledge on the pathogenesis of the disease may allow identification of new therapeutic targets in Sjögren's syndrome.
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