Pathogenetic mechanisms in the initiation and perpetuation of Sjögren's syndrome

Abstract

Sjögren's syndrome (SS), a chronic autoimmune disorder, particularly compromises the function of exocrine glands. The involvement of these glands is characterized by focal, mononuclear cell infiltrates that surround the ducts and replace the secretory units. The pathogenetic mechanisms of this autoimmune exocrinopathy have not been fully elucidated. Immunologically-activated or apoptotic glandular epithelial cells that expose autoantigens in genetically predisposed individuals might drive autoimmune-mediated tissue injury. Alterations in several immune mediators, such as upregulation of type I interferon-regulated genes, abnormal expression of B-cell-activating factor and activation of the interleukin-23-type 17 T-helper cell pathway, have been reported. Extension of the pathological process that affects the exocrine glands into periepithelial and extraepithelial tissue can cause a considerable percentage of patients to exhibit systemic findings that involve the lungs, liver or kidneys. These manifestations develop as a result of lymphocytic invasion or an immune-complex-mediated process, or both, and present as skin vasculitis coupled with peripheral neuropathy or glomerulonephritis (or both). Patients with systemic extraepithelial manifestations display low serum levels of the complement component C4 and mixed type II cryoglobulins, and show an increased risk of developing non-Hodgkin lymphoma, thereby reflecting an overall worse prognosis with higher mortality rates than those without extraepithelial manifestations.

Sjogren’s syndrome variant: A Case Report

“…The underlying inflammation destroys the glands and affects the functioning. [5] Ultrasound examination shows early hyperechoic appearance but shows multicystic appearance in long standing cases as was our case. Cross sectional imaging by CECT and MRI delineate more tissue characterization.…”

Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo¨gren׳s syndrome? Association between clinical, histopathological, and molecular features: A retrospective study

“…Taking into account the pivotal role of GCs in driving B-and Tcell activation, it has been suggested that their presence in the pSS glandular infiltrates may affect the clinical picture and the progression of the disease in several ways [57]: (i) the higher degree of lymphocytic organization may lead to a more pronounced disruption of glandular architecture and secretory function impairment [31,58]; (ii) GC formation may increase lymphocyte activation and function, autoantibody production [57], and immune complex formation, leading to extraglandular manifestations [57][58][59]; and (iii) the development of B-cell NHL seems to rely on antigen-driven stimulation [60].…”

Monocytes from Sjögren's syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis

“…Clinical observations and results from patient cell approaches and animal models of SS point to the loss of salivary gland homeostasis as a triggering factor for the autoimmune response which would, in turn, promote further damage to the gland [6][7][8][9][10][11]. In line with this, evidence of aberrant expression of inflammatory and apoptosis mediators in salivary gland epithelial cells from pSS patients and murine models was reported [12][13][14][15][16][17]. Immune homeostasis depends strongly upon a rapid and immunosuppressant apoptotic cell clearance by monocytes/macrophages to prevent an inflammatory response and self-tolerance breakdown [18][19][20][21].…”