scholarly journals Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice

2015 ◽  
Vol 75 (3) ◽  
pp. 617-622 ◽  
Author(s):  
Barbara M Szczerba ◽  
Paulina Kaplonek ◽  
Nina Wolska ◽  
Anna Podsiadlowska ◽  
Paulina D Rybakowska ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
And Control ◽  
First Time ◽  
Sjögren‘S Syndrome

ObjectivesAutoantibodies reactive with Ro52 are often found in sera of patients with Sjögren's syndrome (SS). This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS.MethodsNew Zealand Mixed (NZM) 2758 mice were immunised with Ro52 in alum adjuvant. Control mice were immunised either with maltose-binding protein or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine-induced salivation. Antibody binding to salivary gland (SG) cells was analysed in vivo and in vitro by immunofluorescence. Sera from immunised mice were passively transferred into untreated or alum injected NZM2758 mice.ResultsBy day 30 post-immunisation, Ro52 immunised mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunised and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunised mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalised by a SG cell line and this uptake was inhibited by cytochalasin D treatment.ConclusionsOur data show for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.

scholarly journals Hepatitis Delta Virus Detected in Salivary Glands of Sjögren’s Syndrome Patients and Recapitulates a Sjögren’s Syndrome-Like Phenotype in Vivo

2016 ◽  
Vol 1 (1) ◽  
pp. 12 ◽  
Author(s):  
Melodie L. Weller ◽  
Matthew R. Gardener ◽  
Zoe C. Bogus ◽  
Michael A. Smith ◽  
Elisa Astorri ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Salivary Gland Tissue ◽  
Gland Tissue ◽  
Sjögren‘S Syndrome ◽  
Delta Virus

Background: Low-level, chronic viral infections have been suspect in the development of select autoimmune diseases, including primary Sjögren’s syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues suggestive of a viral infection. Yet, with this data in hand, a causal link between a viral infection and development of pSS had not been identified. Therefore, a study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease.Methods: A viral microarray was utilized to measure viral transcripts present in salivary gland tissue from patients diagnosed with pSS compared to healthy controls. Murine models of salivary gland localized HDV antigen expression were developed to evaluate the capacity of a chronic HDV signature to trigger the development of a pSS-like phenotype.Results: Through this analysis, two distinct viral profiles were identified, including the increased presence of hepatitis delta virus (HDV) in 50% of pSS patients evaluated. Presence of HDV antigen and sequence were confirmed in minor salivary gland tissue. Patients with elevated HDV levels in salivary gland tissue were negative for detectible hepatitis B virus (HBV) surface antigen and antibodies to HBV or HDV. Expression of HDV antigens in vivo resulted in reduced stimulated saliva flow, increase in focal lymphocytic infiltrates, and development of autoantibodies.Conclusion: Identification of HDV in pSS patients and induction of a complete pSS-like phenotype in vivo provides further support of a viral-mediated etiopathology in the development of pSS.

scholarly journals In Vivo Confocal Microscopy of Meibomian Glands in Sjögren's Syndrome

2011 ◽  
Vol 52 (2) ◽  
pp. 933 ◽  
Author(s):  
Edoardo Villani ◽  
Silvia Beretta ◽  
Michela De Capitani ◽  
Daniela Galimberti ◽  
Francesco Viola ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
In Vivo Confocal Microscopy ◽  
Meibomian Glands ◽  
Sjögren‘S Syndrome

scholarly journals LAMP3 induces apoptosis and autoantigen release in Sjögren’s syndrome patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tsutomu Tanaka ◽  
Blake M. Warner ◽  
Toshio Odani ◽  
Youngmi Ji ◽  
Ying-Qian Mo ◽  
...  
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Minor Salivary Gland ◽  
Palliative Therapy ◽  
Transcriptome Profiling ◽  
Sjogren’S Syndrome ◽  
Underlying Disease ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

Abstract Primary Sjögren’s syndrome (pSS) is a complex autoimmune disease characterized by dysfunction of secretory epithelia with only palliative therapy. Patients present with a constellation of symptoms, and the diversity of symptomatic presentation has made it difficult to understand the underlying disease mechanisms. In this study, aggregation of unbiased transcriptome profiling data sets of minor salivary gland biopsies from controls and Sjögren’s syndrome patients identified increased expression of lysosome-associated membrane protein 3 (LAMP3/CD208/DC-LAMP) in a subset of Sjögren’s syndrome cases. Stratification of patients based on their clinical characteristics suggested an association between increased LAMP3 expression and the presence of serum autoantibodies including anti-Ro/SSA, anti-La/SSB, anti-nuclear antibodies. In vitro studies demonstrated that LAMP3 expression induces epithelial cell dysfunction leading to apoptosis. Interestingly, LAMP3 expression resulted in the accumulation and release of intracellular TRIM21 (one component of SSA), La (SSB), and α-fodrin protein, common autoantigens in Sjögren’s syndrome, via extracellular vesicles in an apoptosis-independent mechanism. This study defines a clear role for LAMP3 in the initiation of apoptosis and an independent pathway for the extracellular release of known autoantigens leading to the formation of autoantibodies associated with this disease. ClinicalTrials.gov Identifier: NCT00001196, NCT00001390, NCT02327884.

Multiple OralCandidaInfections in Patients with Sjögren’s Syndrome — Prevalence and Clinical and Drug Susceptibility Profiles

2011 ◽  
Vol 38 (11) ◽  
pp. 2428-2431 ◽  
Author(s):  
ZHIMIN YAN ◽  
ANDREW L. YOUNG ◽  
HONG HUA ◽  
YANYING XU
Keyword(s):  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Oral Candidiasis ◽  
Sjogren’S Syndrome ◽  
Drug Susceptibility ◽  
Sjogren's Syndrome ◽  
Rapid Screening ◽  
Cross Resistance ◽  
Sjögren‘S Syndrome

Objective.To determine the prevalence of oral candidiasis and multiple oralCandidainfections in patients with primary Sjögren’s syndrome (SS), and the clinical and drug susceptibility profile.Methods.Thirty patients with primary SS were enrolled in our study. The diagnosis of oral candidiasis was based on the clinical manifestation, and confirmed by a concentrated rinse culture.Candidaspp. assessment was accomplished using standard methods: Sabouraud dextrose agar with 50 mg/l chloramphenicol and CHROMagar were used for the rapid screening of clinical species, followed by the API 20C system for further species identification.In vitroantifungal drug susceptibility ofCandidaisolates was determined by the minimal inhibitory concentrations.Results.In our study, 87% (26/30) of subjects had oral candidiasis, in which 42% (11/26) had multipleCandidaspp. infection. AlthoughC. albicansremains the predominant isolate, other rare species such asC. tropicalis,C. glabrata,C. parapsilosis, andC. kruseiwere present, alone or in combination. Chronic atrophic candidiasis is the most common clinical type of oral candidiasis in patients with SS. The susceptibilities of the 44Candidaisolates to 7 antifungal agents varied dramatically. The resistance to azoles was remarkable, and the phenomenon of cross-resistance between itraconazole and fluconazole was observed.Conclusion.Patients with primary SS carry a high risk of oral candidiasis and a high frequency of multipleCandidainfections. The azole resistance patterns ofCandidaspp. support the necessity for drug susceptibility testing as a routine procedure for patients with oralCandidainfections.

Is Sialography Effective in Diagnosing the Salivary Component of Sjögren's Syndrome?

1996 ◽  
Vol 10 (1) ◽  
pp. 25-28 ◽  
Author(s):  
T.E. Daniels ◽  
D.K. Benn
Keyword(s):  
Salivary Glands ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Keratoconjunctivitis Sicca ◽  
Sjogren’S Syndrome ◽  
Salivary Flow ◽  
Sjogren's Syndrome ◽  
Diagnostic Sensitivity And Specificity ◽  
And Control ◽  
Sjögren‘S Syndrome

Parotid sialography has been used for many years as a means of assessing salivary glands in Sjogren's syndrome (SS), and it is occasionally used as a diagnostic criterion for the salivary component of SS. To assess its diagnostic effectiveness, we reviewed studies in which sialography was applied to patients with SS and control subjects for the purpose of estimating its diagnostic sensitivity and specificity or comparing it with other means of assessing salivary glands. Sialography appears to be diagnostically less sensitive but more specific than salivary flow rate measurement and more sensitive but less specific than labial salivary gland (LSG) biopsy. Such calculations are based on the diagnosis of SS established in each study, but the various studies used widely different criteria to establish that diagnosis. Therefore, these calculations are not based on a consistent standard, and comparison between the calculations may be misleading, which underscores the need to develop internationally accepted diagnostic criteria for SS. Studies conducted so far have not shown that parotid sialography is either a sensitive indicator of the salivary component of SS or more closely associated than LSG biopsy with keratoconjunctivitis sicca. the only other component of primary SS with which ultimately to assess diagnostic specificity.

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