scholarly journals Deciphering Molecular and Phenotypic Changes Associated with Early Autoimmune Disease in the Aire-Deficient Mouse Model of Sjögren’s Syndrome

2018 ◽  
Vol 19 (11) ◽  
pp. 3628 ◽  
Author(s):  
Feeling Chen ◽  
Eliza Gaylord ◽  
Nancy McNamara ◽  
Sarah Knox
Keyword(s):  
Cell Survival ◽  
Signaling Pathways ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoimmune Response ◽  
Mild Phenotype ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is characterized by extensive lymphocytic infiltration of the salivary and lacrimal gland (LG), resulting in acinar cell destruction and organ dysfunction. The underlying pathogenesis of SS remains largely unknown, and studies historically focus on defining late-stage disease. Here, we identify tissue programs associated with disease onset using transcriptomic and immunohistological analysis of LGs from 5- and 7-week-old mice deficient in autoimmune response element (Aire). At 5 weeks of age (wk), Aire-/- mice show minimal tissue dysfunction and destruction compared to 7 wk Aire-/-, which exhibit severe dry eye, poor tear secretion, extensive lymphocytic infiltration, reduced functional innervation, and increased vascularization. Despite this mild phenotype, 5 wk Aire-/- LGs were highly enriched for signaling pathways previously associated with SS, including interferon gamma (IFNγ), interleukin 1 beta (IL1β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), toll-like receptor (TLR) signaling, and interleukin-6/signal transducer and activator of transcription 3 (IL6/STAT3) signaling. Novel signaling pathways such as the semaphorin–plexin pathway were also noted. Intriguingly, we found an expansion of the ductal network with increasing disease. Activated STAT3, a blocker of apoptosis, was restricted to the ductal system and also increased with damage, highlighting its potential as a promoter of ductal cell survival. These data demonstrate the early activation of signaling pathways regulating inflammation, innervation, and cell survival before the onset of clinical disease indicators, suggesting their potential value as diagnostic biomarkers.

scholarly journals Sjogren’s Syndrome Presenting with Solely Cutaneous Features

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1260
Author(s):  
Sneha Centala ◽  
Joyce H. Park ◽  
Diana Girnita
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Systemic Disease ◽  
Relapsing Polychondritis ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Initial Symptom ◽  
Sjögren‘S Syndrome

Sjogren’s syndrome is classically characterized by symptoms of keratoconjunctivitis sicca and xerostomia, secondary to lymphocytic infiltration of the salivary and lacrimal glands. Cutaneous findings of this disease are infrequently discussed and thus rarely considered among patients without the typical symptomatology. However, these patients can develop xerosis, alopecia, vitiligo, papular or nodular lesions, or cutaneous vasculitis. A 56-year-old Asian female presented with intermittent cutaneous erythematous lesions of her bilateral pinna and preauricular areas. Despite initial symptom presentation causing concern for tumid lupus versus cutaneous T cell lymphoma versus relapsing polychondritis, extensive serologic and histopathologic workup eventually indicated a likely diagnosis of Sjogren’s syndrome. This case brings to light that Sjogren’s syndrome is truly a multi-systemic disease and can present with primarily extra glandular cutaneous symptoms. When approaching the workup of a new patient, it is absolutely vital to maintain a broad differential and keep in mind that overlap syndromes among multiple autoimmune diseases do exist as well.

Abnormal Histones Acetylation In Patients With Primary Sjögren’s Syndrome

2020 ◽  
Author(s):  
Yan Li ◽  
Xiuying Lv ◽  
Mi Zhou ◽  
Yan He ◽  
Ying Wang ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Histone H3 ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Tnf Α ◽  
Spearman Test ◽  
Sjögren‘S Syndrome

Abstract Background pSS is an autoimmune disease characterized by an exocrine gland epithelium injury with dense lymphocytic infiltration, involvement of the peripheral nervous, pulmonary, blood, kidney, skin, and joint. Aberrant histone acetylation is increasingly thought to plays important role in the pathogenesis of AIDs. However, there is very little data on histone acetylation in pSS. Methods We investigated the expressions of HAT genes (p300, CREEBP and PCAF) by real time PCR in PBMCs from pSS patients. HAT activity and histone H3/ H4 acetylation activity measured by activity kit and histone H3/H4 acetylation verified by WB. Spearman test was utilized to analyze the association between levels of HAT activity and clinical parameters of patients with pSS. Results The expressions of p300, CREEBP and PCAF in PBMCs from pSS patients were decreased in mRNA comparison with HCs. HAT activity and histone H3/H4 acetylation were reduced in PBMCs from pSS patients. We found negatively correlations between the HAT activity and CRP and TNF-α, and positively correlations between the HAT activity and C4. Conclusions Histone hypoacetylation is observed in patients with pSS and involved in the disease duration of Sjogren's syndrome.

scholarly journals MicroRNA in Sjögren’s Syndrome: Their Potential Roles in Pathogenesis and Diagnosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
M. Reale ◽  
C. D’Angelo ◽  
E. Costantini ◽  
M. Laus ◽  
A. Moretti ◽  
...  
Keyword(s):  
B Cells ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Exocrine Glands ◽  
Autoantibody Production ◽  
Systemic Autoimmunity ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) or sicca syndrome was described by Swedish ophthalmologist Sjögren in the year 1933 for the first time. The etiology of the SS is multifunctional and includes a combination of genetic predisposition and environmental as well as epigenetic factors. It is an autoimmune disease characterized by features of systemic autoimmunity, dysfunction, and inflammation in the exocrine glands (mainly salivary and lacrimal glands) and lymphocytic infiltration of exocrine glands. In fact, the involvement of lacrimal and salivary glands results in the typical features of dry eye and salivary dysfunction (xerostomia). Only in one-third of the patients also present systemic extraglandular manifestations. T cells were originally considered to play the initiating role in the autoimmune process, while B cells were restricted to autoantibody production. In recent years, it is understood that the roles of B cells are multiple. Moreover, autoantibodies and blood B cell analysis are major contributors to a clinical diagnosis of Sjögren’s syndrome. Recently, there has been rising interest in microRNA implication in autoimmunity. Unfortunately, to date, there are only a few studies that have investigated their participation in SS etiopathogenesis. The purpose of this work is to gather the data present in the literature to clarify this complex topic.

Altered Autoantigen Structure in Sjögren’s Syndrome: Implications for the Pathogenesis of Autoimmune Tissue Damage

2004 ◽  
Vol 15 (3) ◽  
pp. 156-164 ◽  
Author(s):  
A. Rosen ◽  
L. Casciola-Rosen
Keyword(s):  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Tissue Damage ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Autoimmune Response ◽  
Immune Effector ◽  
Effector Pathways ◽  
Sjögren‘S Syndrome

The etiology and pathogenic mechanisms underlying Sjögren’s syndrome (SS) remain unclear. Recent studies have emphasized that the specific autoantibodies that occur in a high proportion of patients with SS may provide important insights into the circumstances that initiate and propagate tissue damage in this disease. Although autoantigens targeted in systemic autoimmune diseases share little in common in terms of structure, subcellular distribution, or function in normal cells, these molecules are unified by becoming clustered and concentrated in the surface blebs of apoptotic cells. Furthermore, their structure is altered during some types of cell death to generate structures not previously generated during development and homeostasis. This review highlights the susceptibility of SS autoantigens to undergoing such structural changes during activation of immune effector pathways, and synthesizes a model of SS incorporating these concepts. An understanding of the mechanisms responsible for activating the specific immune response in SS, and the role of specific immune effector pathways in propagating both the autoimmune response and tissue damage, is of potential therapeutic importance. Abbreviations used in this paper are: CTL, cytotoxic T-lymphocytes; ER, endoplasmic reticulum; GluR3, subunit III of the glutamate receptor; GrB, granzyme B; M3R, type III muscarinic receptor; NK cells, natural killer cells; PARP, poly(ADP-ribose)polymerase; SS, Sjögren’s syndrome; SLE, systemic lupus erythematosus; and UV, ultraviolet.

Beta2Microglobulin and Lymphocytic Infiltration in Sjögren's Syndrome

1975 ◽  
Vol 293 (24) ◽  
pp. 1228-1231 ◽  
Author(s):  
Joseph P. Michalski ◽  
Troy E. Daniels ◽  
Norman Talal ◽  
Howard M. Grey
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Lacrimal gland fluid secretion and lymphocytic infiltration in the NZB/W mouse model of Sjögren’s syndrome

2001 ◽  
Vol 23 (3) ◽  
pp. 199-205 ◽  
Author(s):  
Yelena Paranyuk ◽  
Nidia Claros ◽  
Aija Birzgalis ◽  
Leon C. Moore ◽  
Peter R. Brink ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Lacrimal Gland ◽  
Sjögren's Syndrome ◽  
Fluid Secretion ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals PUF60: a prominent new target of the autoimmune response in dermatomyositis and Sjögren's syndrome

2015 ◽  
Vol 75 (6) ◽  
pp. 1145-1151 ◽  
Author(s):  
David F Fiorentino ◽  
Matthew Presby ◽  
Alan N Baer ◽  
Michelle Petri ◽  
Kerri E Rieger ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Inclusion Body ◽  
Lupus Erythematosus ◽  
Inclusion Body Myositis ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Peptide Sequencing ◽  
Sjogren's Syndrome ◽  
Autoimmune Response ◽  
Sjögren‘S Syndrome

ObjectivesAutoantibodies are used clinically to phenotype and subset patients with autoimmune rheumatic diseases. We detected a novel 60 kDa autoantibody specificity by immunoblotting using a dermatomyositis (DM) patient's serum. Our objective was to identify the targeted autoantigen and to evaluate disease specificity and clinical significance of this new autoantibody.MethodsA new 60 kDa specificity was detected by immunoblotting HeLa cell lysates. The targeted autoantigen was identified as poly(U)-binding-splicing factor 60 kDa (PUF60) using (i) a human protein array and (ii) two-dimensional gel electrophoresis and liquid chromatography tandem mass spectrometry peptide sequencing. Anti-PUF60 antibodies were assayed by ELISA using sera from patients with primary Sjögren's syndrome (SS; n=84), systemic lupus erythematosus (SLE; n=71), DM (n=267), polymyositis (n=45), inclusion body myositis (n=45) and healthy controls (n=38).ResultsPUF60 was identified as a new autoantigen. Anti-PUF60 antibodies were present in 25/84 (30%) patients with SS, 6/71 (8.5%) patients with SLE and 2/38 (5.0%) control subjects (SS vs controls, p=0.002; SLE vs controls, p=0.711). Anti-PUF60 antibodies were present in 48/267 (18.0%) patients with DM versus 4/45 (8.9%) and 5/45 (11.1%) patients with inclusion body myositis and polymyositis, respectively. The antibody was significantly associated with anti-Ro52 antibodies, rheumatoid factor and hyperglobulinemia in the patients with primary SS. In patients with DM, the antibody was associated with anti-transcription intermediary factor 1 gamma seropositivity and Caucasian race.ConclusionsPUF60 represents a novel autoantigen in patients with SS and DM. PUF60 antibodies are associated with distinct clinical features and different immune responses in different diseases.

scholarly journals MANAGEMENT OF SJOGREN'S SYNDROME THROUGH AYURVEDA : A CASE STUDY

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dr Raja Singla ◽  
Dr Harish Kumar
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Autoimmune Disorder ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Exocrine Glands ◽  
Dry Eyes ◽  
Sjögren‘S Syndrome

Sjögren's syndrome is a chronic, slowly progressing autoimmune disorder characterised by lymphocytic infiltration of exocrine glands resulting in xerostomia and dry eyes (conjunctivitis). 1) The disease can present as an entity alone or in association with other auto-immune diseases like Scleroderma, RA, SLE & auto-immune thyroid disease. 2) In this article, attempt is made to understand the Sjögren's syndrome & its treatment in ayurveda by considering the concept of udakvaha srotodushti, vyadhikshamatva and vatadhikya vatrakta. Keywords:Auto-immune, Vatadhikya Vatrakta, Sjögren's syndrome, Udakvaha srotodushti

Sjögren's syndrome involing the larynx: report of a case

1979 ◽  
Vol 93 (9) ◽  
pp. 933-936 ◽  
Author(s):  
David M. Barrs ◽  
Thomas J. McDonald ◽  
Joseph Duffy
Keyword(s):  
Differential Diagnosis ◽  
Sjögren’S Syndrome ◽  
Lower Respiratory Tract ◽  
Sjögren's Syndrome ◽  
Lymphocytic Infiltration ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren’S Disease ◽  
Laryngeal Involvement ◽  
Sjögren‘S Syndrome

Synopsis-AbstractSJÖGREN's syndrome is a presumably autoimmune disease with parthologic findings of lymphocytic infiltration of the involved structures. Although the salivary and lacrimal gl ands are the most commonly involved sites, extragl andular lymphoproliferation also occurs. Upper and lower respiratory tract lymphoproliferation is known, but only one case of Sjögren's disease of the larynx has been previously reported. We present a case of laryngeal involvement in which the gross pathologic appearance is different from that in the earlier case report. The otolaryngologist should consider Sjögren's disease in the differential diagnosis of diffuse laryngeal lesions.

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