Inflammation in Sjögren's syndrome: Cause or consequence?

Abstract

Sjögren's syndrome (SS) is an autoimmune disease most commonly characterized by ocular and oral dryness. Despite the high prevalence of SS, generation and perpetuation of this disease is still unclear in many aspects. Inflammation, nonetheless, seems to play a central role in this pathology especially in the form of Th-1, Th-2 and Th-17 cytokines release within different aspects, concentrations and connections involved in the maintenance of the syndrome. Moreover, the chronically created pro-inflammatory environment appears to promote glandular atrophy and irreparable architectural modifications. The establishment of germinal centers (GC) in SS are considered the main reason for the 16-times increased probability of lymphoproliferative disease development in these patients. SS is also interconnected with numerous others auto-inflammatory and autoimmune diseases, many of them representing the first clear sign of a dysregulated immune system. Despite the recent advances, treatment options are still insufficient. This overview aims to better elucidate this local and systemic disease, which can be of vital use not only for SS but also to other rheumatic pathological conditions.

Cathepsin S Alters the Expression of Pro-Inflammatory Cytokines and MMP-9, Partially through Protease—Activated Receptor-2, in Human Corneal Epithelial Cells

“…Concurrent with and sometimes even preceding the lymphocytic infiltration characteristic of SS, altered levels of pro-inflammatory cytokines and other inflammatory mediators are found in LG and salivary glands of SS mouse models, and also in glands of SS patients [ 56 , 57 , 58 ]. These mediators are also found in tears and conjunctival epithelium [ 15 ], and it is thought that their release from the inflamed LG may impact the ocular surface.…”

Long Non-Coding RNAs Modulate Sjögren’s Syndrome Associated Gene Expression and Are Involved in the Pathogenesis of the Disease

“…Leukocyte infiltration in the damaged pSjS glandular epithelium enhances the inflammatory environment that also is sustained by epithelial cell production of adhesion molecules and chemokines [78]. Several proinflammatory pathways were targeted by the selected lncRNAs, including signaling by TNF/NF-Kb (LINC00657), p38 MAP kinase (CTD-2020K17.1), IFN-gamma (LINC00657, LINC00511 and CTD-2020K17.1), GMCSF (LINC00657, LINC00511 and CTD-2020K17.1) and IL-8 (LINC00657).…”

Decrease in alpha-1 antiproteinase antitrypsin is observed in primary Sjogren’s syndrome condition

“…The oral and salivary manifestations observed in pSS include dry mouth, difficulty in chewing and swallowing food, and oral burning symptoms [5][6][7]. Importantly, clinical manifestations from primary pSS patients and animal models of SS point to the loss of salivary gland function that results from abnormal autoimmune response; however, the mechanism that initiates loss of salivary gland secretion is not well understood [8,9]. Extra glandular manifestations are also common for these patients, who show an enhanced lymphoproliferation, with a greater risk of forming malignant lymphoma.…”

“…Extra glandular manifestations are also common for these patients, who show an enhanced lymphoproliferation, with a greater risk of forming malignant lymphoma. Histologically, pSS is characterized by extensive lymphocytic infiltration that is observed in the salivary and lacrimal gland tissues [8][9][10][11][12] and secretion of proteases, such as serine proteases, could induce the loss of salivary glands. Importantly, salivary gland cells have a measure that can protect them against the proteases secreted by immune cells; however, if these protective mechanisms are lost, they may induce cell death [9,13,14].…”