Update on Pathogenesis of Sjogren's Syndrome

Abstract

Sjögren’s syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjögren’s syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis – the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental factors are also being explored. SS also has some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed.

Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations

“…In both subgroups, most of the modulated genes belonged to the same few biological processes that are known to be peculiarly activated in pSS . However, only in the GFs group were genes involved in sensory and pain perception modulated.…”

“…The differences in gene expression in the two subgroups of pSS patients, with opposite phenotypic features, appear more evident when looking at the PPI network cluster analysis and the related enriched pathway analysis. The most interconnected genes modulated in patients with EGMs belong to pathways involved in innate (apoptosis, TLR and IFN signaling, proinflammatory cytokines) and adaptive (T‐ and B‐cell activation and cooperation) immune responses, which are largely documented in many biological studies as playing fundamental roles in pSS .…”

Associations between alopecia areata and multiple sclerosis: a report of two cases and review of the literature

“…Sjogren's syndrome shows the involvement of both T and B cells, with CD4+ Th1 cells playing a greater role than CD8+ T cells. Similarly to AA and MS, SS presents an imbalance of Th17 and Tregs, tipped in favor of Th17 …”

“…Similarly to AA and MS, SS presents an imbalance of Th17 and Tregs, tipped in favor of Th17. 17 In autoimmune thyroiditis, both subtypes of T helper, Th1 and Th2, are involved. An elevated level of Th17 cells in young patients with untreated Hashimoto's disease has also been reported, which suggests the contribution of these cells in the induction and development of thyroiditis.…”

Recent advances of exosomes in immune-mediated eye diseases

“…This condition leads to one of the most severe subtypes of dry eye diseases [20]. Activation of both innate and adaptive immune pathways, such as interferon (IFN) signatures, B cell activating factor (BAFF)/BAFF receptor axis, and NF-kB signaling, contributes to the pathogenesis of SS [69,70].…”