Treatment of Sjögren's Syndrome with Mesenchymal Stem Cells: A Systematic Review.

Mesenchymal stem cells (MSCs) are ubiquitous in the human body. Mesenchymal stem cells were initially isolated from bone marrow and later from other organs such as fatty tissues, umbilical cords, and gingiva. Their secretory capacities give them interesting immunomodulatory properties in cell therapy. Some studies have explored the use of MSCs to treat Sjögren's syndrome (SS), a chronic inflammatory autoimmune disease that mainly affects exocrine glands, including salivary and lacrimal glands, although current treatments are only palliative. This systematic review summarizes the current data about the application of MSCs in SS. Reports show improvements in salivary secretions and a decrease in lymphocytic infiltration in salivary glands in patients and mice with SS after intravenous or infra-peritoneal injections of MSCs. MSC injections led to a decrease in inflammatory cytokines and an increase in anti-inflammatory cytokines. However, the intrinsic mechanism of action of these MSCs currently remains unknown.

Mediterranean diet and risk of Sjögren's syndrome.

OBJECTIVES: Non-genetic risk factors for Sjögren's syndrome (SS) are poorly understood. Adherence to a Mediterranean diet has been associated with reduction in other autoimmune diseases. We examined the association of Mediterranean diet with SS. METHODS: New patients attending a single centre warranting investigation for primary SS (pSS) were recruited into the Optimising Assessment in Sjögren's Syndrome cohort established in Birmingham, UK (2014-2018). Participants were classified into pSS and non-SS sicca, considered as cases and non-cases, respectively, and asked to complete an optional food frequency questionnaire on their diet before onset of symptoms. A semi-quantitative Mediterranean diet score (MDS) was calculated (possible range=0 to 18). Using multivariate logistic regression, corrected for energy intake, body-mass index, sex, age, symptom duration, and smoking status, we examined the association of MDS with SS. RESULTS: Dietary data were available for 133/243 (55%) eligible patients (n=82 pSS and n=51 sicca). In the adjusted model, a higher total MDS (mean ± SD, 9.41±2.31 points) was associated with lower odds of pSS (OR 0.81, 95% CI 0.66-0.99; p=0.038) per one unit of MDS. Among MDS components, the strongest association was seen with fish with OR 0.44 (95% CI 0.24-0.83; p=0.01) in the comparison between <1 portion/week and 1 to 2.5 portions/week. Higher galactose, vitamin A-retinol-equivalents and vitamin C showed associations with lower odds of pSS in multivariate analysis, where the association of vitamin C was attenuated when adjusted for MDS. CONCLUSIONS: When adjusted for potential confounders, adherence to the Mediterranean diet was associated with lower likelihood of having pSS.

Calidad de vida oral en pacientes con síndrome de Sjögren primario / Oral health-related quality of life in primary Sjögren's syndrome

OBJETIVO: Evaluar la calidad de vida general y oral, y sus correlaciones con el flujo salival no estimulado (FSNE) y los síntomas de xerostomía en pacientes con síndrome de Sjögren primario (SSP). MÉTODOS: Se incluyeron 60 pacientes con SSP y 60 controles pareados por género y ±3 años de edad. Se midió el FSNE y se aplicó cuestionario ESSPRI (Cuestionario reportado de síntomas en Síndrome de Sjögren de la Liga Europea contra el reumatismo [EULAR]). Se utilizó la versión corta de SF-36 para evaluar calidad de vida general, y para la calidad de vida oral el cuestionario XeQoLS; así como 8 preguntas para evaluar síntomas orales (dificultad al hablar, tragar, cantidad de saliva en boca, sequedad de boca, garganta, labios, lengua y nivel de sed) mediante escalas visuales análogas (EVA). RESULTADOS: Observamos peor calidad de vida general (menor puntuación SF-36), oral (mayor puntuación XeQoL) y mayor sintomatología evaluada por EVA en pacientes vs. controles. El XeQoL correlacionó con el FSNE (tau = −0,24, p = 0,008), el ESSPRI (tau = 0,45, p = 0,0001), las preguntas EVA 1-2 y EVA 5-8 y la escala SF-36 (tau = 0,28, p = 0,002). CONCLUSIONES: Los pacientes con SSP tienen peor calidad de vida general y oral que sujetos sanos. El FSNE contribuye en la calidad de vida oral y a su vez la calidad de vida oral impacta en la calidad de vida general. La intervención oportuna de terapia sintomática de xerostomía y la prevención de infecciones, caries y pérdida dental pudiera impactar la calidad de vida de estos pacientes

OBJECTIVE: To assess health-related quality of life (HRQoL) and oral health-related quality of life, and correlate them with unstimulated whole salivary flow (UWSF) and oral sicca symptoms in patients with primary Sjögren's syndrome (PSS). METHODS: We included 60 patients with PSS and 60 healthy controls matched according to gender and age (±3 years). We measured the UWSF and scored the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI). We assessed the short version of the SF-36 as a generic measurement of HRQoL and the Xerostomia Quality of Life Scale (XeQoLS) questionnaire to evaluate oral quality of life. We evaluated oral symptoms using an 8-item Visual Analogue Scale (VAS) questionnaire. RESULTS: We observed a poorer HRQoL (lower scores in SF-36) and oral quality of life (higher scores in XeQoLS), as well as a greater severity of symptoms in the VAS questionnaire upon comparing patients vs. controls. The XeQoL correlated with the UWSF (Tau = −0.24, P = .008), the ESSPRI (Tau =0.45, P = .0001), VAS 1-2 and VAS 5-8 and the SF-36 score (Tau = −0.28, P = .002). CONCLUSIONS: Patients with PSS had a poorer HRQoL and oral quality of life than controls. UWSF contributes to the oral quality of life which, in turn, has an impact on HRQoL. Symptomatic treatment of xerostomia as well as the prevention of infections, decay and tooth loss would help to improve the oral quality of life in these patients

Agonist-induced 4-1BB activation prevents the development of SjÓ§gren's syndrome-like sialadenitis in non-obese diabetic mice.

Activation of costimulatory receptor 4-1BB enhances T helper 1 (Th1) and CD8 T cell responses in protective immunity, and prevents or attenuates several autoimmune diseases by increasing Treg numbers and suppressing Th17 or Th2 effector response. We undertook this study to elucidate the impact of enforced 4-1BB activation on the development of Sjögren's syndrome (SS)-like sialadenitis in non-obese diabetic (NOD) model of this disease. An anti-4-1BB agnostic antibody was intraperitoneally injected to female NOD mice aged 7 weeks, prior to the disease onset that occurs around 10-11 weeks of age, 3 times weekly for 2 weeks, and the mice were analyzed for SS pathologies at age 11 weeks. The salivary flow rate was markedly higher in the anti-4-1BB-treated NOD mice compared to the IgG-treated controls. Anti-4-1BB treatment significantly reduced the leukocyte infiltration of the submandibular glands (SMGs) and the levels of serum antinuclear antibodies. Flow cytometric analysis showed that the percentages of CD4 T cells, Th17 cells and plasmacytoid dendritic cells among SMG leukocytes were markedly reduced by anti-4-1BB treatment, in conjunction with a reduction in SMG IL-23p19 mRNA levels and serum IL-17 concentrations. Although the proportion of Tregs and IL-10 mRNA levels in SMGs were not altered by 4-1BB activation, IL-10 mRNA levels in salivary gland-draining lymph nodes and serum IL-10 concentrations were both markedly increased. While anti-4-1BB treatment did not affect the amount of Th1 cells and IFNγ mRNA in the SMGs, it increased these measurables in salivary gland-draining lymph nodes. Hence, agonistic activation of 4-1BB impedes the development of SS-like sialadenitis and hyposalivation.

Relationship between sjögren syndrome and periodontal status: A systematic review.

OBJECTIVE: This study aimed to examine whether Sjögren syndrome (SS) is related to periodontal status. STUDY DESIGN: A systematic review was performed on the basis of PRISMA (PROSPERO: CRD42017055202). A search was performed in the PubMed/MEDLINE, LILACS, Web of Science, and Science Direct databases. Hand searches and review of the gray literature were also performed. Three researchers independently selected studies, extracted data, and assessed methodologic quality. Studies that correlated primary and/or secondary SS with plaque index, gingival index, probing depth, and bleeding on probing were included. The risk of bias was estimated on the basis of the Newcastle-Ottawa scale. RESULTS: Seventeen studies were included in the review and 9 included in the meta-analysis, with a total of 518 and 544 patients, with or without SS, respectively. The mean difference of plaque index (0.29; 95% confidence interval [CI] 0.17-0.41), gingival index (0.52; 95% CI 0.14-0.89), and bleeding on probing (9.92; 95% CI 4.37-15.47) were larger in patients with SS than in controls. In primary SS (0.47; 95% CI 0.10-0.83) and secondary SS (0.74; 95% CI 0.10-1.38), only the mean gingival index was larger compared with that in control group. The majority of the included studies were judged as having a high risk of bias. CONCLUSIONS: The present review did not provide strong evidence that periodontal status is affected by SS.

Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice.

BACKGROUND & AIMS: Sjögren's syndrome and autoimmune pancreatitis are disorders with decreased function of salivary, lacrimal glands, and the exocrine pancreas. Nonobese diabetic/ShiLTJ mice and mice transduced with the cytokine BMP6 develop Sjögren's syndrome and chronic pancreatitis and MRL/Mp mice are models of autoimmune pancreatitis. Cystic fibrosis transmembrane conductance regulator (CFTR) is a ductal Cl- channel essential for ductal fluid and HCO3- secretion. We used these models to ask the following questions: is CFTR expression altered in these diseases, does correction of CFTR correct gland function, and most notably, does correcting ductal function correct acinar function? METHODS: We treated the mice models with the CFTR corrector C18 and the potentiator VX770. Glandular, ductal, and acinar cells damage, infiltration, immune cells and function were measured in vivo and in isolated duct/acini. RESULTS: In the disease models, CFTR expression is markedly reduced. The salivary glands and pancreas are inflamed with increased fibrosis and tissue damage. Treatment with VX770 and, in particular, C18 restored salivation, rescued CFTR expression and localization, and nearly eliminated the inflammation and tissue damage. Transgenic overexpression of CFTR exclusively in the duct had similar effects. Most notably, the markedly reduced acinar cell Ca2+ signaling, Orai1, inositol triphosphate receptors, Aquaporin 5 expression, and fluid secretion were restored by rescuing ductal CFTR. CONCLUSIONS: Our findings reveal that correcting ductal function is sufficient to rescue acinar cell function and suggests that CFTR correctors are strong candidates for the treatment of Sjögren's syndrome and pancreatitis.

Estrés oxidativo en las enfermedades bucales / Oxidative stress in the oral illnesses

Introducción: toda enfermedad está basada en trastornos a nivel molecular, por lo que el profesional de la salud debe interpretar las variadas manifestaciones internas de las enfermedades producidas por alteraciones de las biomoléculas que interactúan sistémicamente, en las cuales tienen un papel importante el estrés oxidativo. Objetivo: realizar una revisión bibliográfica sobre el estrés oxidativo y las enfermedades que afectan a la cavidad bucal. Métodos: se realizó una revisión bibliográfica en el periodo comprendido entre septiembre de 2014 a enero de 2016. Se consultaron las bases de datos de sistemas referativos, como MEDLINE, PubMed y SciELO con la utilización de descriptores como oxidative stress in oral deseases y su contraparte en español. Se incluyeron artículos en idioma inglés y español y publicaciones de los últimos cinco años, solo seis con mayor tiempo de publicación. Se revisaron 110 artículos, y se circunscribió el estudio a 49 que enfocaron estas temáticas de manera más integral. Análisis e integración de los resultados: tiene el estrés oxidativo gran relación con la enfermedad periodontal, la mucositis, los estados pulpares, síndrome de Sjögren, síndrome de ardor bucal, aftas bucales y lesiones premalignas como leucoplasia y liquen plano bucal. Conclusiones: existe relación entre el estrés oxidativo y muchas enfermedades que afectan la cavidad bucal, lo que influye en la patogenia de estas(AU)

Introduction: the basis of disease is the occurrence of disorders at the molecular level, so the health professional should be able to understand the varied internal manifestations of a disease caused by alterations in the biomolecules that systemically interact and the important role that the oxidative stress plays in this process. Objective: to make a literature review on the oxidative stress and the diseases affecting the oral cavity. Methods: a literature review was made in the period of September 2014 through January 2016. MEDLINE, PubMed and SciELO databases were consulted; the subject headings were oxidative stress in oral diseases in Spanish and in English. Several articles in English and Spanish and publications of the last five years, in addition to 6 articles published prior to this period, were all included. A total of 110 articles were reviewed, but for the study, 49 were selected on account of a more comprehensive approach on these topics.Data analysis and integration: the oxidative stress is closely related to periodontal disease, mucositis, pulpal diseases, Sjögren syndrome, burning mouth syndrome, oral aphthas and premalignant lesions such as leukoplakia and oral lichen planus. Conclusions: there is association of the oxidative stress and many other diseases affecting the oral cavity, which has an impact on the pathogenesis of many diseases(AU)

Estrés oxidativo en las enfermedades bucales / Oxidative stress in the oral illnesses

Introducción: toda enfermedad está basada en trastornos a nivel molecular, por lo que el profesional de la salud debe interpretar las variadas manifestaciones internas de las enfermedades producidas por alteraciones de las biomoléculas que interactúan sistémicamente, en las cuales tienen un papel importante el estrés oxidativo. Objetivo: realizar una revisión bibliográfica sobre el estrés oxidativo y las enfermedades que afectan a la cavidad bucal. Métodos: se realizó una revisión bibliográfica en el periodo comprendido entre septiembre de 2014 a enero de 2016. Se consultaron las bases de datos de sistemas referativos, como MEDLINE, PubMed y SciELO con la utilización de descriptores como oxidative stress in oral deseases y su contraparte en español. Se incluyeron artículos en idioma inglés y español y publicaciones de los últimos cinco años, solo seis con mayor tiempo de publicación. Se revisaron 110 artículos, y se circunscribió el estudio a 49 que enfocaron estas temáticas de manera más integral. Análisis e integración de los resultados: tiene el estrés oxidativo gran relación con la enfermedad periodontal, la mucositis, los estados pulpares, síndrome de Sjögren, síndrome de ardor bucal, aftas bucales y lesiones premalignas como leucoplasia y liquen plano bucal. Conclusiones: existe relación entre el estrés oxidativo y muchas enfermedades que afectan la cavidad bucal, lo que influye en la patogenia de estas.(AU)

Introduction: the basis of disease is the occurrence of disorders at the molecular level, so the health professional should be able to understand the varied internal manifestations of a disease caused by alterations in the biomolecules that systemically interact and the important role that the oxidative stress plays in this process. Objective: to make a literature review on the oxidative stress and the diseases affecting the oral cavity. Methods: a literature review was made in the period of September 2014 through January 2016. MEDLINE, PubMed and SciELO databases were consulted; the subject headings were oxidative stress in oral diseases in Spanish and in English. Several articles in English and Spanish and publications of the last five years, in addition to 6 articles published prior to this period, were all included. A total of 110 articles were reviewed, but for the study, 49 were selected on account of a more comprehensive approach on these topics. Data analysis and integration: the oxidative stress is closely related to periodontal disease, mucositis, pulpal diseases, Sjögren syndrome, burning mouth syndrome, oral aphthas and premalignant lesions such as leukoplakia and oral lichen planus. Conclusions: there is association of the oxidative stress and many other diseases affecting the oral cavity, which has an impact on the pathogenesis of many diseases(AU)

Smad4 in T cells plays a protective role in the development of autoimmune Sjögren's syndrome in the nonobese diabetic mouse.

We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway, in T cells on the pathology of Sjögren's syndrome (SS) in nonobese diabetic (NOD) mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre; Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration into exocrine glands, decreased tear and saliva production, and increased levels of autoantibodies at 12 weeks of age. Activated/memory T cells and cytokine (IFN-γ, IL-17)-producing T cells were increased in Smad4 tKO NOD mice, however the proportion and function of regulatory T (Treg) cells were not different between Smad4 tKO and WT NOD mice. Effector T (Teff) cells from Smad4 tKO NOD mice were less sensitive than WT Teff cells to suppression by Treg cells. Th17 differentiation capability of Teff cells was similar between Smad4 tKO and WT NOD mice, but IL-17 expression was increased under inducible Treg skewing conditions in T cells from Smad4 tKO NOD mice. Our results demonstrate that disruption of the Smad4 pathway in T cells of NOD mice increases Teff cell activation resulting in upregulation of Th17 cells, indicating that Smad4 in T cells has a protective role in the development of SS in NOD mice.

Glutathione protects against hepatic injury in a murine model of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease which may cause complications such as hepatic dysfunction and injury. As an important antioxidant, reduced glutathione (GSH) has been reported protecting against hepatic injury induced by some diseases, but the role of GSH in pSS is poorly understood. This study aims at investigating the role of GSH in hepatic injury during pSS. A murine model of pSS, non-obese diabetic (NOD) mice, was used for GSH administration via tail intravenous injection. Enzyme-linked immunosorbent assay (ELISA) was performed to detect serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of GSH, tumor necrosis factor, interleukin (IL) 10, integrin alpha M, IL1B, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase 4, and superoxide dismutases in hepatocyte homogenates. Hematoxylin-eosin staining was performed to observe hepatic histology. The results showed that serum AST and ALT levels were up-regulated in the NOD mice (p = 0.0021 and 0.0048), but were significantly recovered after the GSH administration (p = 0.0081 and 0.0263). The NOD mice exhibited disturbed hepatic tissue structure, which was attenuated by GSH. The GSH administration could also promote the production of GSH in the hepatocytes (p = 0.0264), and control the levels of inflammatory factors and oxidative stress-related factors. These results indicate that GSH has significant effects on protecting against the hepatic injury during pSS, which may be associated with its regulation of the inflammatory factors and oxidative stress-related factors. This study suggests that GSH is a promising therapeutic strategy for controlling hepatic injury during pSS and offers valuable information for further research.

Secondary Amyloid Deposition in Discoid Lupus Erythematosus / Depósitos de amiloide secundarios a lupus eritematoso discoide

No disponible

Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction.

Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS.

Sjögren's syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090.

Sjögren's syndrome is an autoimmune disease associated with inflammation of exocrine glands with clinical manifestations of dry eye and dry mouth. Dry eye in this disease involves inflammation of the ocular surface tissues - cornea and conjunctiva. While systemic blockade of adhesion molecules has been used to treat autoimmune diseases, the purpose of this study was to determine the therapeutic efficacy of topical application of an integrin α4 adhesion molecule antagonist in a mouse model of dry eye associated with Sjögren's syndrome. To assess this spontaneously developed ocular surface inflammation related to Sjögren's syndrome in TSP-1null mice (12 wks) was evaluated. Mice were treated with topical formulations containing 0.1% dexamethasone or 30 mg/ml GW559090 or vehicle control. Corneal fluorescein staining and conjunctival goblet cell density were assessed. Real-time PCR analysis was performed to assess expression of the inflammatory marker IL-1ß in the cornea and Tbet and RORγt in the draining lymph nodes. Ocular surface inflammation was detectable in TSP-1null mice (≥12 wk old), which resulted in increased corneal fluorescein staining indicative of corneal barrier disruption and reduced conjunctival goblet cell density. These changes were accompanied by increased corneal expression of IL-1ß as compared to WT controls and an altered balance of Th1 (Tbet) and Th17 (RORγt) markers in the draining lymph nodes. Topically applied dexamethasone and GW559090 significantly reduced corneal fluorescein staining compared to vehicle treatment (p = 0.023 and p < 0.001, respectively). This improved corneal barrier integrity upon adhesion molecule blockade was consistent with significantly reduced corneal expression of pro-inflammatory IL-1ß compared to vehicle treated groups (p < 0.05 for both treatments). Significant improvement in goblet cell density was also noted in mice treated with 0.1% dexamethasone and GW559090 (p < 0.05 for both). We conclude that similar to topical dexamethasone, topically administered GW559090 successfully improved corneal barrier integrity and inflammation in an established ocular surface disease associated with Sjögren's syndrome.

Avaliação dos efeitos do tratamento periodontal não cirúrgico sobre os sinais e sintomas da síndrome de Sjõgren primária / Evaluation of periodontal non-surgical treatment effects on the signs and symptoms on primary Sjõgren's syndrome

A síndrome de Sjõgren primária (SSp) é uma doença crônica autoimune sistêmica que pode levar à hipossalivação e afetar negativamente o ambiente oral. Os objetivos deste estudo foram detectar a influência da SSp nos níveis de biomarcadores inflamatórios na saliva e no fluido gengival nas amostras de pacientes com periodontite crônica, avaliar o efeito do tratamento periodontal não cirúrgico sobre os valores do índice clínico de avaliação da atividade sistêmica de pacientes com SSp e do índice reportado pelo paciente com SSp. Amostras de fluido gengival, saliva e os parâmetros clínicos periodontais que consistiram de medida da profundidade de sondagem (PS), nível clínico de inserção (NCI), sangramento à sondagem (SS) e índice de placa (IP) foram coletadas no início do estudo e 45 dias após a terapia periodontal não-cirúrgica de pacientes sistemicamente saudáveis com periodontite crônica (PC, n = 7) e pacientes com SSp e periodontite crônica (SP, n = 7). Pacientes periodontalmente saudáveis com SSp (SC, n = 7) e sistemicamente saudáveis (C, n = 7) também foram avaliados no início do estudo. Os grupos C, PC e SC foram pareados em gênero, idade e critério socioeconômico com o grupo SP. Os níveis de interleucina-8 (IL-8), IL-10 e IL-1ß foram avaliados por ensaio multiplex. Os níveis de atividade da doença foram medidos usando o Gold Standard da literatura chamado Índice Eular de atividade da síndrome de Sjõgren (ESSDAI). Já para avaliação dos sintomas reportados pelo paciente com SSp foi utilizado o Índice Eular reportado pelo paciente com Sjõgren (ESSPRI).

Os parâmetros clínicos melhoraram após a terapia periodontal (p <0,05). No entanto, o NCI em pacientes com SSp não melhorou significativamente após a terapia (p> 0,05). Houve um aumento nos níveis de IL-1ß, IL-8 e diminuição dos níveis de IL-10 nas amostras de saliva de pacientes do grupo SC em comparação ao grupo C (p <0,05). Já em relação ao fluido gengival, pacientes do grupo SC tiveram maiores níveis de IL-1ß em comparação com o grupo C (p<0,05). Além disso, o tratamento periodontal não cirúrgico resultou num aumento dos níveis de IL-10 no fluido gengival no grupo SP e grupo PC em relação ao valor basal (p <0,05). O fluxo salivar foi significativamente aumentado após o tratamento periodontal apenas em pacientes do grupo SP (p = 0,039). Além disso, o tratamento periodontal não influenciou o índice ESSDAI (p = 0,35) e levou a uma diminuição significativa no índice ESSPRI (p = 0,03). Os presentes dados demonstraram que a SSp influencia os níveis salivares e de fluido gengival de biomarcadores inflamatórios em favor de um perfil próinflamatório, no entanto, este perfil parece não aumentar susceptibilidade dos indivíduos SSp à destruição periodontal. Além disso, os presentes dados demonstraram que o tratamento periodontal não-cirúrgico tem um impacto positivo sobre o fluxo salivar e sobre o índice ESSPRI de pacientes com SSp. Sugere-se assim que o tratamento periodontal pode melhorar a qualidade de vida de indivíduos com SSp.

Primary Sjõgren's syndrome (pSS) is a chronic systemic autoimmune disease that might lead to hyposalivation and negatively affect the oral environment. The aims of this study were to detect the influence of pSS on the levels of inflammatory biomarkers in salivary and gingival crevicular fluid (GCF) samples of patients with chronic periodontitis and to evaluate the effect of non-surgical periodontal treatment on the disease activity index of patients with pSS, and on the reported index of patients with pSS. GCF and salivary samples and clinical parameters consisting of measuring probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were collected at baseline and 45 days after non-surgical periodontal therapy from systemically healthy patients with chronic periodontitis (PC, n=7) and patients with pSS with chronic periodontitis (SP, n=7). Periodontally healthy patients with pSS (SC, n=7) and systemically healthy (C, n=7) were also evaluated at baseline. The groups C, PC and SC were pared on gender, years and socioeconomic status with the SP group. The levels of interleukin-8 (IL-8), IL-10, and IL-1ß were measured by using multiplex immunoassays. Disease activity levels were measured by using the Gold Standard called Eular Sjõgren's syndrome disease activity index (ESSDAI). Also to evaluate the symptoms reported by the pacients with pSS we used the Eular Sjõgren's syndrome patient reported index (ESSPRI).

The clinical parameters improved significantly after periodontal therapy (p<0.05). However, CAL in pSS patients was not statistically improved after therapy (p>0.05). There was an increased expression of IL-1ß, IL-8 and decreased levels of IL-10 in the salivary samples of patients in the group SC compared to the group C (p<0.05). The GCF, patients in the group SC had bigger levels of IL-1ß in comparation with the C group (p<0.05). Moreover, nonsurgical periodontal treatment resulted in increased levels of IL-10 on GCF in the groups SP and PC in relation to the baseline (p<0.05). Salivary flow was significantly increased post-treatment only in the SP's group patients (p=0.039). In addition, periodontal treatment did not influence ESSDAI index (p=0.35) and led to a statistically significant decrease on the ESSPRI index (p=0.03). The present data demonstrated that pSS influences the salivary and GCF levels of inflammatory biomarkers in favour of a proinflammatory profile, however, this profile might doesn't increase the susceptibility of pSS subjects to periodontal breakdown. In addition, the present data demonstrated that non-surgical periodontal treatment has a positive impact on the salivary flow and ESSPRI index of pSS patients. Thus suggesting that periodontal treatment may improve the quality of life of pSS subjects.

Síndrome de Sjögren / No disponble

No disponible

Activation of HIF-1α (hypoxia inducible factor-1α) prevents dry eye-induced acinar cell death in the lacrimal gland.

The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sjögren's syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sjögren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1α. Interestingly, the areas of stable HIF-1α expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1α conditional knockout (CKO) mice in which HIF-1α expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sjögren's syndrome, CD3(+) and CD11b(+) cells infiltrated HIF-1α CKO LGs. Our results show that DE induced the expression of HIF-1α that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.

Perforación corneal como primera manifestación de síndorme de Sjören secundario a artritis reumatoide / Corneal melts as the initial manifestation of sjögren syndrome secondary to rheumatoid arthritis

La artritis reumatoide es una enfermedad sistémica inflamatoria crónica frecuente, de etiología desconocida. El síndrome de Sjögren puede ir asociado a dicha patología. El curso clínico de la artritis reumatoide a nivel ocular es muy variable y el diagnóstico temprano es determinante para prevenir graves complicaciones. Presentamos el caso de una mujer de 64 años de edad que acudió al Servicio de Urgencias por presentar ojo rojo bilateral con fotofobia, lagrimeo continuo, dolor y disminución de la agudeza visual. En la exploración se objetivó importante adelgazamiento del estroma corneal en OD y perforación corneal OI, que requirió recubrimiento tectónico con membrana amniótica. Los análisis serológicos mostraron los siguientes resultados: Factor Reumatoide+, ANA+, ENA Anti-Ro/SSA+, ENA Anti-La/SSB+. La paciente fue diagnosticada de Artritis Reumatoide y Síndrome de Sjögren secundario. Desde entonces, sigue un tratamiento sistémico con corticoides y azatioprina. Aproximadamente, el 25% de los pacientes desarrollan enfermedad oftalmológica, esencialmente queratoconjuntivitis seca (25%), epiescleritis, escleritis y queratitis. Estas manifestaciones son en general poco severas, pero hay un pequeño porcentaje de pacientes, como el caso que aquí presentamos, que sufren una inflamación ocular grave y que sin tratamiento inmunosupresor precozmente instaurado, pueden desarrollar úlceras corneales estériles, centrales o periféricas, que les puede llevar incluso a la perforación y destrucción del globo (AU)

Rheumatoid arthritis(RA) is a common chronic inflammatory autoinmune disease, with unknown etiology. Approximately 11-31% of RA patients have secondary Sjögren´s syndrome. Ophthalmologic manifestations of these diseases can cause corneal scarring, ulceration, infection, and even perforation; thus, although the prognosis is good for most patients with Sjögren syndrome and ophthalmologic features, individuals with complications have much guarded prognosis. We report the case of a 65 years old woman with photophobia, pain, tearing and blurred vision in both eyes. Slit lamp exam showed an important corneal melting right eye, and corneal perforation left eye, which required amniotic membrane transplantation. The diagnosis was: Rheumatoid Arthritis and secondary Sjögren´s Syndrome. Azathioprine treatment was started in combination with oral steroids. Approximately 25% of patients have ocular involvement, and keratoconjunctivitis sicca is the most frequent ocular complication. Although the prognosis is good in most cases, an early diagnosis is necessary to avoid several complications (AU)

Effects of total glucosides of paeony for delaying onset of Sjogren's syndrome: an animal study.

OBJECTIVE: To investigate the effectiveness of total glucosides of paeony (TGP) on Sjogren's syndrome (SS) using non-obese diabetic (NOD) mice model. STUDY DESIGN: Twenty-seven 8-week-old female NOD mice were assigned into TGP group, hydroxychloroquine (HCQ) group and normal saline (NS) group, receiving corresponding drugs respectively and sacrificed at 24-week-old. Saliva flow rate (SFR), ration of regulatory T cells, level of anti-SSA/SSB, histological changes in submandibular glands (SMG) and microarray analysis were assessed. The data were analyzed using SPSS. RESULTS: Compared to NS group, in TGP group, SFR, SMG index and the ration of regulatory T cells were significantly higher, while anti-SSA/SSB and lymphocytic foci were significantly lower. HCQ group demonstrated similar results except SMG index. Altered gene expression was found in 10.71% of TGP and 13.09% of HCQ of the profile. CONCLUSION: TGP demonstrated a similar effectiveness as HCQ in delaying the onset of SS-like disease in NOD mice.

Influence of sex hormones and genetic predisposition in Sjögren's syndrome: a new clue to the immunopathogenesis of dry eye disease.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration, destruction of lacrimal and salivary glands and the presence of serum autoantibodies. Most women that suffer from SS are post-menopausal however, not all post-menopausal women develop SS, suggesting that other factors, in addition to the decrease in ovarian hormones, are necessary for the development of SS. The purposes of this study were to investigate a) the time course of lymphocytic infiltration and apoptosis in the lacrimal gland after ovariectomy, b) if a predisposed genetic background for SS aggravates the effects of decreasing levels of sex hormones in the lacrimal glands and c) if physiological doses of estrogen or androgen prevent the effects observed after ovariectomy. Six weeks old mice that are genetically predisposed to SS (NOD.B10.H2(b)) and control (C57BL/10) mice were either sham operated, ovariectomized (OVX), OVX + 17ß estradiol (E(2)) or OVX + Dihydrotestosterone (DHT). Lacrimal glands were collected at 3, 7, 21 or 30 days after surgery and processed for immunohistochemistry to measure CD4(+), CD8(+) T cells, B220(+) B cells, nuclear DNA degradation and cleaved caspase-3 activity. Quantification of the staining was done by light microscopy and Image Pro Plus software. The results of our study show that lymphocytic infiltration preceded lacrimal gland apoptosis after ovariectomy. Moreover, removal of ovarian sex hormones accelerated these effects in the genetically predisposed animal and these effects were more severe and persistent compared to control animals. In addition, sex hormone replacement at physiological levels prevented these symptoms. The mechanisms by which decreased levels of sex hormones caused lymphocytic infiltration and apoptosis and the interaction of lack of sex hormones with the genetic elements remain to be elucidated.