scholarly journals Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Nabangshu Das ◽  
Nikhil G. Menon ◽  
Luiz G. N. de Almeida ◽  
Paige S. Woods ◽  
Miriam L. Heynen ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Interleukin 12 ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Neutrophil Degranulation ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tear and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Pathway enrichment analysis of the changing proteins by Metascape identified leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation in tears of SS patients. In healthy controls’ tears, an enrichment for proteins related to glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients’ saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls’ saliva, an enrichment for proteins related to JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients’ tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings will improve our mechanistic understanding of the disease and changes in SS patients’ protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

scholarly journals POS0109 IDENTIFICATION OF PRIMARY SJOGREN’S SYNDROME SUBTYPES BY MACHINE LEARNING

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 265.2-266
Author(s):  
M. T. Qiu ◽  
S. X. Zhang ◽  
J. Qiao ◽  
J. Q. Zhang ◽  
S. Song ◽  
...  
Keyword(s):  
Machine Learning ◽  
Sjögren’S Syndrome ◽  
Immune Cells ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Sjögren‘S Syndrome

Background:Sjogren’s syndrome(pSS) is a chronic, progressive, and systematic autoimmune disease characterized by lymphocytic infiltration of exocrine glands 1 2. Sicca symptoms and abnormal fatigue are the main clinical presentation, but those symptoms are non-specific to patients, which lead to delayed diagnosis 1 3. The heterogeneous of clinical manifestation raise challenges regarding diagnosis and therapy in pSS, thus it’s necessary for us to sub-classify pSS.Objectives:To explore new biomarkers for diagnosis and subtypes of pSS based on Machine Learning Primary.Methods:All microarray raw datas (CEL files) were screened and downloaded from Gene Expression Omnibus (GEO). Meta-analysis to identify the consistent DEGs by MetaOmics. Weighted gene co-expression network analysis (WGCNA) was used to the modules related to SS for further analysis. Subclasses were computed using a consensus Non-negative Matrix Factorization (NMF) clustering method. Immune cell infiltration was used to evaluate the expression of immune cells and obtain various immune cell proportions from samples. P value < 0.05 were considered statistically significant. All the analyses were conducted under R environment (version 4.03).Results:A total of 3715 consistent DEGs were identified from the four datasets, including 1748 up-regulated and 1967 down-regulated genes. Tour meaningful modules, including yellow, turquoise, grey60 and bule, were identified (Figure 1A,1B). And 183 overlapping gene were screened from the DEGs and the Hub genes in the four modles for further analysis. We final divided pSS patients into three subtypes, of which yellow and turquoise in Sub1, grey60 in Sub2 and blue in Sub3. Sub1 and Sub3 were related to cell metabolism, while Sub2 had connection with virus infection (Figure 1C,1D). Infiltrated immune cells were also different among these three types (Figure 1E,1F).Conclusion:Patients with pSS could be classified into 3 subtypes, this classification might help for assessing prognosis and guiding precise treatment.References:[1]Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Primary Sjogren syndrome. BMJ (Clinical research ed) 2012;344:e3821. doi: 10.1136/bmj.e3821 [published Online First: 2012/06/16].[2]Brito-Zeron P, Baldini C, Bootsma H, et al. Sjogren syndrome. Nat Rev Dis Primers 2016;2:16047. doi: 10.1038/nrdp.2016.47 [published Online First: 2016/07/08].[3]Segal B, Bowman SJ, Fox PC, et al. Primary Sjogren’s Syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes 2009;7:46. doi: 10.1186/1477-7525-7-46 [published Online First: 2009/05/29].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals POS0776 CORRELATION OF PERIPHERAL CD4+GRANZB+CTLS WITH DISEASE SEVERITY IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.3-642
Author(s):  
Q. Wang ◽  
L. Gu ◽  
M. Zhang
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Sjögren’S Syndrome ◽  
Mhc Class Ii ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Extraglandular Manifestations ◽  
Sjögren‘S Syndrome

Background:Sjögren’s syndrome (SS) is a chronic autoimmune disorder. The major histopathologic lesion of it is a focal lymphocytic infiltrate around ductal and acinar epithelial cells, which include a majority of CD4+T. Several studies have shown that the epithelial cells in SS present diverse phenomena, such as MHC class II overexpression. CD4+T cells with cytotoxic activity (CD4 CTL) have been detected in various immune responses. They are characterized by their ability to secrete perforin and granzyme B to kill the target cells in an MHC class II-restricted fashion.Objectives:So this study was to investigate the correlation of peripheral CD4+GranzB+CTLs with disease severity and organ involvement in patients with primary Sjögren’s syndrome.Methods:We recruited 116 pSS patients and 46 healthy controls using flow cytometry to examine proportion of CD4+GranzB+CTLs in their peripheral blood, and immunofluorescence to test the expression of CD4+GranzB+CTLs in labial gland. The correlations of CD4+GranzB+CTLs and the relevant clinical data were analyzed.Results:We analyzed the percentage of CD4+GranzB+cytotoxic T cells in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Frequency of peripheral CD4+GranzB+CTLs were measured in 116 patients with pSS and 46 healthy controls matched for age and sex. The percentage of CD4+GranzB+CTLs were significantly up-regulated in pSS patients than healthy controls (7.1%±4.9% vs 3.1%±1.9%, p <0.0001) and positive correlation with ESSDAI in pSS patients(r = 0.6332, p<0.001). The percentage of CD4+GranzB+CTLs were markedly higher in pSS patients with extraglandular manifestations. Moreover, CD4+GranzB+CTLs were observed in the lymphocytic foci and periductal areas of the LSGs and were elevated with increased foci index (FI). After excluding the other risk factors associated with pSS, CD4+GranzB+CTLs were still related to ESSDIA and extraglandular manifestations independently(p<0.05). ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS, and 0.851 to presume extraglandular manifestations. The best diagnostic cut-off point was 4.865 for pSS patients.Conclusion:In this study, We provide new evidence indicating involvement of CD4+GranzB+CTLs over activation in the disease pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.References:[1]Takeuchi A, Saito T. Front Immunol. (2017) 23:194.[2]Brown DM, et al. Front Immunol. (2016) 9:93.[3]Polihronis M, et al. Clin Exp Immunol. (1998) 114:485-90.[4]Xanthou G, et al. Clin Exp Immunol. (1999) 118:154-63.[5]Maehara T, et al. Ann Rheum Dis. (2017) 76:377-385.[6]Goules AV, et al. Clin Immunol. (2017) 182:30-40.[7]Hashimoto K, et al. Proc Natl Acad Sci U S A. (2019) 116:24242-24251.[8]Croia C, et al. Arthritis Rheumatol. (2014) 66:2545-57.[9]Schmidt D,et al. J Clin Invest. (1996) 97:2027–37.[10]Pandya JM, et al. Arthritis Rheum. (2010) 62:3457–66.[11]Moosig F, et al. Clin Exp Immunol. (1998) 114:113–8.[12]Peeters LM, et al. Front Immunol. (2017) 20:1160.Table 1.Multivariate analysis of CD4+GranzB+CTLs influenced by pSS-related factorsregression coefficientstandard errort-statisticsp value95%CICD8+GranzB+CTLs(%)0.1440.0334.3346.9E-50.077, 0.211ESSDAI0.2560.1222.0950.0410.011, 0.502extraglandular manifestations2.6121.2682.0590.0450.065, 5.158Figure 1.Receiver operating characteristic (ROC) curve of the frequency of CD4+GranzB+CTLs to predict ESSDAI and extraglandular manifestations responseDisclosure of Interests:None declared

Levels of plasmacytoid dendritic cells and type-2 myeloid dendritic cells are reduced in peripheral blood of patients with primary Sjögren's syndrome

2009 ◽  
Vol 69 (6) ◽  
pp. 1235-1238 ◽  
Author(s):  
Petra Vogelsang ◽  
Johan G Brun ◽  
Gunnvor Øijordsbakken ◽  
Kathrine Skarstein ◽  
Roland Jonsson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Sjögren’S Syndrome ◽  
Peripheral Blood ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Healthy Controls ◽  
Myeloid Dendritic Cells ◽  
Antigen Presenting ◽  
Sjögren‘S Syndrome

ObjectiveSjögren's syndrome (SS) is a lymphoproliferative autoimmune disease, characterised by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells crucial for initiating and maintaining primary immune responses. This study quantified interferon-producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in peripheral blood (PB) from primary SS (pSS) patients and healthy controls.MethodsBlood samples from 31 pSS patients and 28 gender and age-matched healthy controls were analysed by flow cytometry using the Miltenyi Blood DC enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analysed by immunohistochemistry.ResultsPatients with pSS had significantly less pDC and mDC2 in PB compared with healthy controls. Moreover, pDC are present in SG from patients with pSS.ConclusionPatients with pSS have alterations among DC populations in PB, and pDC are present in the SG, suggesting a potential role of these cells in SS.

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 Contributions of Major Cell Populations to Sjögren’s Syndrome

2020 ◽  
Vol 9 (9) ◽  
pp. 3057 ◽  
Author(s):  
Richard Witas ◽  
Shivai Gupta ◽  
Cuong Q. Nguyen
Keyword(s):  
B Cell ◽  
Sjögren’S Syndrome ◽  
Mouse Models ◽  
Immune Cells ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
B Cell Lymphoma ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a female dominated autoimmune disease characterized by lymphocytic infiltration into salivary and lacrimal glands and subsequent exocrine glandular dysfunction. SS also may exhibit a broad array of extraglandular manifestations including an elevated incidence of non-Hodgkin’s B cell lymphoma. The etiology of SS remains poorly understood, yet progress has been made in identifying progressive stages of disease using preclinical mouse models. The roles played by immune cell subtypes within these stages of disease are becoming increasingly well understood, though significant gaps in knowledge still remain. There is evidence for distinct involvement from both innate and adaptive immune cells, where cells of the innate immune system establish a proinflammatory environment characterized by a type I interferon (IFN) signature that facilitates propagation of the disease by further activating T and B cell subsets to generate autoantibodies and participate in glandular destruction. This review will discuss the evidence for participation in disease pathogenesis by various classes of immune cells and glandular epithelial cells based upon data from both preclinical mouse models and human patients. Further examination of the contributions of glandular and immune cell subtypes to SS will be necessary to identify additional therapeutic targets that may lead to better management of the disease.

scholarly journals Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

2020 ◽  
Vol 117 (12) ◽  
pp. 6630-6639 ◽  
Author(s):  
Verónica C. Martínez Allo ◽  
Vanesa Hauk ◽  
Nicolas Sarbia ◽  
Nicolás A. Pinto ◽  
Diego O. Croci ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Gland ◽  
Sjögren’S Syndrome ◽  
Immune Cell ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Lymphoid Cells ◽  
Age Related ◽  
Sjögren‘S Syndrome

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1−/−) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren’s syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking β1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating β1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+regulatory T cells (Tregs), and increased number of CD8+T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren’s syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.

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