Development of autoimmune arthritis with aging via bystander T cell activation in the mouse model of Sjögren's syndrome

2004 ◽  
Vol 50 (12) ◽  
pp. 3974-3984 ◽  
Author(s):  
Masaru Kobayashi ◽  
Natsuo Yasui ◽  
Naozumi Ishimaru ◽  
Rieko Arakaki ◽  
Yoshio Hayashi
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
T Cell Activation ◽  
Cell Activation ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoimmune Arthritis ◽  
Sjögren‘S Syndrome

scholarly journals A distinguishing profile of chemokines, cytokines, and biomarkers in the saliva of children with Sjögren’s syndrome

Rheumatology ◽  
2021 ◽  
Author(s):  
M Paula Gomez Hernandez ◽  
Emily E Starman ◽  
Andrew B Davis ◽  
Miyuraj Harishchandra Hikkaduwa Withanage ◽  
Erliang Zeng ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
T Cell Activation ◽  
Cell Activation ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Children ◽  
Immune System Diseases ◽  
Cell Functions ◽  
Sjögren‘S Syndrome

Abstract Objectives Sjögren’s syndrome is an autoimmune disease most commonly diagnosed in adults but can occur in children. Our objective was to assess the presence of chemokines, cytokines, and biomarkers (CCBMs) in saliva from these children that were associated with lymphocyte and mononuclear cell functions. Methods Saliva was collected from 11 children diagnosed with Sjögren’s syndrome prior to age 18 years and 16 normal healthy children. 105 CCBMs were detected in multiplex microparticle-based immunoassays. ANOVA and t test (0.05 level) were used to detect differences. Ingenuity Pathway Analysis (IPA) was used to assess whether elevated CCBMs were in annotations associated with immune system diseases and select leukocyte activities and functions. Machine learning methods were used to evaluate the predictive power of these CCBMs for Sjögren’s syndrome and were measured by receiver operating characteristic (ROC) curve and area under curve (AUC). Results 40.9% (43/105) CCBMs were different (p < 0.05) in children with Sjögren’s syndrome compared to the healthy study controls and could differentiate the two groups (p < 0.05). Elevated CCBMs in IPA annotations were associated with autoimmune diseases and with leukocyte chemotaxis, migration, proliferation, and regulation of T-cell activation. The best AUC value in ROC analysis was 0.93, indicating that there are small numbers of CCBMs that may be useful for diagnosis of Sjögren’s syndrome. Conclusion While 35/43 CCBMs have been previously reported in Sjögren’s syndrome, 8 CCBMs had not. Additional studies focusing on these CCBMs may provide further insight into disease pathogenesis and may contribute to diagnosis of Sjögren’s syndrome in children.

Sjögren’s syndrome

2020 ◽  
pp. 4532-4537
Author(s):  
Wan-Fai Ng
Keyword(s):  
Sjögren’S Syndrome ◽  
Cell Activation ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Association Studies ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Exocrine Glands ◽  
Lymphocytic Infiltrates ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome is an autoimmune connective tissue disease characterized by dryness of the eyes and mouth and lymphocytic infiltrates in the salivary, lachrymal, and other exocrine glands. Its cause is not known, but it may be primary or associated with other autoimmune diseases (secondary) and it affects women more than men (ratio 9–15:1). The aetiology of SS remains elusive, although genetic susceptibility and environmental triggers both play a role. Genome-wide association studies have identified several disease-susceptibility loci. Infections with various viruses have been associated with an SS-like syndrome. Current evidence suggests that environmental or endogenous antigen triggers immune cell activation and autoantibody production, leading to a self-perpetuating inflammatory response in genetically susceptible individuals, and resulting in destruction of exocrine glands.

scholarly journals Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren’s syndrome with ectopic germinal centres and MALT lymphoma

2020 ◽  
Vol 79 (12) ◽  
pp. 1588-1599 ◽  
Author(s):  
Elena Pontarini ◽  
William James Murray-Brown ◽  
Cristina Croia ◽  
Davide Lucchesi ◽  
James Conway ◽  
...  
Keyword(s):  
T Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Pcr Analysis ◽  
Organ Cultures ◽  
Cytokine Detection ◽  
Costimulatory Pathway ◽  
Sjögren‘S Syndrome

ObjectivesTo explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren’s syndrome (SS) patients.MethodsSalivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production.ResultsTranscriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4+CXC-motif chemokine receptor 5 (CXCR5)+programmed cell death protein 1 (PD1)+ICOS+ Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4+CD45RO+ICOS+PD1+ cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5+CD4+PD1+ICOS+Foxp3- Tfh-cells and a uniquely expanded population of CXCR5-CD4+PD1hiICOS+Foxp3- Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α).ConclusionsOverall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.

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