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1.
Medicine (Baltimore) ; 100(12): e23940, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761629

RESUMO

ABSTRACT: To identify the prevalence and clinical characteristics of Sjögren syndrome (SS) in a Chinese single-center cohort of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.Patients diagnosed with SS were screened out from a cohort of 164 cases of SAHPO syndrome. Information regarding the patients' gender, age at onset, clinical features, laboratory tests, bone scintigraphy, and treatment was reviewed.Five patients were screened out. The prevalence of SS in SAPHO patients was 3.05% The mean onset age of SS was 48.0 ±â€Š12.0 years old and no apparent time order in the occurrence of SAPHO and SS was observed. Compared with the general SAPHO cohort, the 5 SS patients exhibited no significant difference in the SAPHO related clinical features or inflammatory markers, except for a higher prevalence of peripheral joints and bones involvement in bone scintigraphy. Objective evidence of dryness and positive salivary gland biopsy were found in all the patients. However, the positive rates of SSA and SSB antibody were only 20%. Anti-inflammatory treatment for SS was recorded in 3 patients (ESSDAI score: 3 in 2 patients; 12 in 1 patient) with extra-glandular manifestations, severe complications or poor response to the basic treatment.The prevalence of SS is higher in the SAPHO cohort than in the general Chinese population. Objective tests or biopsy might be more indicative than the antibody detection for SS diagnosis. Anti-inflammatory treatment should be prescribed in consideration of both the severity of SS and the demand for disease activity control of SAPHO.


Assuntos
Síndrome de Hiperostose Adquirida/epidemiologia , Síndrome de Sjogren/epidemiologia , Síndrome de Hiperostose Adquirida/imunologia , Adulto , Idade de Início , Anti-Inflamatórios/uso terapêutico , Biópsia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Glândulas Salivares/patologia , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia , Tomografia Computadorizada por Raios X
2.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431459

RESUMO

Primary Sjögren's syndrome (pSS) is a chronic slowly progressive autoimmune disease characterised by lymphocytic infiltration of salivary and lacrimal glands with varying degree of systemic involvement. Renal involvement, a recognised extraglandular manifestation of pSS, is commonly related to tubular dysfunction and generally manifests as distal renal tubular acidosis (RTA), proximal RTA, tubular proteinuria and nephrogenic diabetes insipidus. Untreated long-standing RTA is known to cause metabolic bone disease. Here, we present the report of a patient with sclerotic metabolic bone disease related to pSS with combined distal and proximal RTA and negative workup for other causes of sclerotic bone disease. A significant clinical and biochemical improvement, including recovery of proximal tubular dysfunction, was noted with alkali therapy. This case suggests the need to consider pSS in the diagnostic algorithm of a patient presenting with sclerotic bone disease.


Assuntos
Acidose Tubular Renal/diagnóstico , Dor nas Costas/imunologia , Doenças Ósseas Metabólicas/diagnóstico , Síndrome de Sjogren/diagnóstico , Absorciometria de Fóton , Acidose Tubular Renal/sangue , Acidose Tubular Renal/tratamento farmacológico , Acidose Tubular Renal/imunologia , Adulto , Fosfatase Alcalina/sangue , Dor nas Costas/sangue , Densidade Óssea/imunologia , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/imunologia , Feminino , Humanos , Citrato de Potássio/uso terapêutico , Cintilografia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Esqueleto/diagnóstico por imagem , Bicarbonato de Sódio/uso terapêutico
3.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440862

RESUMO

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by the infiltration of exocrine glands including salivary and lachrymal glands responsible for the classical dry eyes and mouth symptoms (sicca syndrome). The spectrum of disease manifestations stretches beyond the classical sicca syndrome with systemic manifestations including arthritis, interstitial lung involvement, and neurological involvement. The pathophysiology underlying SS is not well deciphered, but several converging lines of evidence have supported the conjuncture of different factors interplaying together to foster the initiation and perpetuation of the disease. The innate and adaptive immune system play a cardinal role in this process. In this review, we discuss the inherent parts played by both the innate and adaptive immune system in the pathogenesis of SS.


Assuntos
Imunidade Adaptativa , Suscetibilidade a Doenças/imunologia , Imunidade Inata , Síndrome de Sjogren/imunologia , Animais , Comunicação Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Especificidade de Órgãos/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
4.
Am J Kidney Dis ; 77(3): 440-453, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33487481

RESUMO

The understanding and management of membranous nephropathy, a common cause of nephrotic syndrome that is more frequently encountered in adults than in children, has rapidly evolved over the past decade. Identification of target antigens has allowed for more precise molecular diagnoses, and the ability to monitor circulating autoantibodies has added a new vantage point in terms of disease monitoring and decisions about immunosuppression. Although immunosuppression with alkylating agents combined with corticosteroids, or with calcineurin inhibitor-based regimens, has been the historical mainstay of treatment, observational and now randomized controlled trials with the B-cell-depleting agent rituximab have moved this agent to the forefront of therapy for primary membranous nephropathy. In this Core Curriculum, we discuss the typical features of primary and secondary disease; highlight the target antigens such as the phospholipase A2 receptor, thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1, and semaphorin-3B; describe the relationship between the immunologic and clinical courses of disease; and review modern management with supportive care or immunosuppressive treatment based on these composite parameters.


Assuntos
Autoanticorpos/imunologia , Glomerulonefrite Membranosa/imunologia , Proteínas de Ligação ao Cálcio/imunologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/imunologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Malária/complicações , Glicoproteínas de Membrana/imunologia , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/imunologia , Neoplasias/complicações , Receptores da Fosfolipase A2/imunologia , Rituximab/uso terapêutico , Semaforinas/imunologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Trombospondinas/imunologia
5.
Mol Immunol ; 131: 112-120, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33446393

RESUMO

BACKGROUND: Networks formed of numerous autoantibodies (aabs) directed against G-protein coupled receptors (GPCR) have been suggested to play important role in autoimmune disorders. In present study, we aimed to evaluate the association between anti-GPCR antibodies and primary Sjogren's syndrome (pSS) to determine the potential pathogenic factors. METHODS: By applying a cell membrane-based ELISA technique, which is capable of detecting aabs against conformational epitopes within GPCR, serum levels of fourteen GPCR were determined in well-characterized patients with pSS (n = 52) and gender-matched healthy controls (n = 54). Comparisons between groups were analyzed by two-tailed Mann-Whitney U test, Bonferroni correction was applied for multiple comparisons. Spearman`s rank correlation coefficients were calculated between variables and visualized by heat map. RESULTS: Compared to healthy subjects, sera of patients with pSS showed significantly higher binding to ß2AR and ETAR, but lower binding to C5aR1, C3aR1, CXCR3, and CXCR4. Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 were also decreased in patients with rheumatoid arthritis. In pSS patients, levels of anti-CXCR3 and anti-CXCR4 antibodies were negatively correlated with circulating lymphocyte counts. Furthermore, correlation signatures of anti-GPCR antibodies changed dramatically in the patients with pulmonary involvement. CONCLUSIONS: This study demonstrates an association between pSS and autoantibodies recognizing GPCR, especially those functionally involved in immune cell migration and exocrine glandular secretion.


Assuntos
Autoanticorpos/imunologia , Receptor da Anafilatoxina C5a/imunologia , Receptores CXCR3/imunologia , Receptores CXCR4/imunologia , Receptores de Complemento/imunologia , Síndrome de Sjogren/imunologia , Adulto , Idoso , Animais , Artrite Reumatoide/imunologia , Células CHO , Estudos de Casos e Controles , Cricetulus , Feminino , Humanos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade
6.
J Leukoc Biol ; 109(2): 437-447, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33325085

RESUMO

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease, characterized by lymphocytic infiltration into exocrine glands, which causes dry eyes, dry mouth, and systemic damage. Although the precise etiology of pSS is not clear yet, highly activated B cells, abundant anti-SSA/Ro, and anti-SSB/La autoantibodies are the hallmarks of this disease. Follicular helper T cells (Tfh), a subset of CD4+ T cells, with cell surface receptors PD-1 and CXCR5, express ICOS, transcription factor Bcl-6, and a cytokine IL-21. These cells help in the differentiation of B cells into plasma cells and stimulate the formation of germinal center (GC). Previous studies have demonstrated abundant Tfh cells in the peripheral blood and salivary glands (SGs) of the patients with pSS, correlated with extensive lymphocytic infiltration of the SGs and high disease activity scores. Patients with pSS who are treated with abatacept (CTLA-4 Ig) show fewer circulating Tfh cells, reduced expression of ICOS, and lower disease activity scores. Recently identified follicular regulatory T (Tfr) cells, a subset of regulatory T cells, control the function of Tfh cells and the GC reactions. Here, we summarize the observed alterations in Tfh and Tfr cell numbers, activation state, and circulating subset distribution in pSS. Our goal is to improve the understanding of the roles of Tfh and Tfr cells (surface marker expression, cytokine production, and transcription factors) in the pathogenesis of pSS, thus contributing to the identification of candidate therapeutic agents for this disease.


Assuntos
Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Linfócitos T Reguladores/imunologia , Animais , Modelos Animais de Doenças , Humanos , Memória Imunológica , Modelos Imunológicos
7.
Phytomedicine ; 80: 153381, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33086170

RESUMO

BACKGROUND: Hyperactivation of B cells by activators has been demonstrated to play a central role in the pathogenesis of Sjögren's syndrome (SS). In this study, we found that artesunate (ART) can attenuate BAFF-induced B cell hyperactivation and SS-like symptoms in NOD/Ltj mice. PURPOSE: To determine the efficacy of ART in attenuating SS-like symptoms in vivo and explore the underlying mechanism in vitro. STUDY DESIGN: ART was intragastrically injected into SS-like NOD/Ltj mice. The cytokine hsBAFF was used to activate Raji and Daudi B cells to mimic B cell hyperactivation in vitro. METHODS: The efficacy of ART in inhibiting SS progression was studied in NOD/Ltj mice. Salivary flow rate, the number of lymphocytic infiltration foci, the level of autoantibodies and the extent of B cell infiltration were measured in the indicated groups. CCK-8 assays, flow cytometry-based EdU staining and Annexin V/PI staining were also used to detect the effect of ART on the survival and proliferation mechanism in BAFF-induced Raji and Daudi cells. Further studies determined that TRAF6 degradation is a potential mechanism by which ART determines B cell fate. RESULTS: Treatment with ART inhibited lymphocytic foci formation, B cell infiltration and autoantibody secretion in SS-like NOD/Ltj mice. In vitro assay results indicated that ART effectively inhibited BAFF-induced viability, survival and proliferation of neoplastic B cells. Mechanistically, ART targeted BAFF-activated NFκB by regulating the proteasome-mediated degradation of TRAF6 in Raji and Daudi cells. CONCLUSION: ART ameliorated murine SS-like symptoms and regulated TRAF6-NFκB signaling, thus determining survival and proliferation of B cells.


Assuntos
Artesunato/farmacologia , Fator Ativador de Células B/farmacologia , Linfócitos B/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Síndrome de Sjogren/imunologia , Animais , Autoanticorpos/metabolismo , Autoimunidade/efeitos dos fármacos , Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfócitos/efeitos dos fármacos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos NOD , NF-kappa B/metabolismo , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/patologia
8.
PLoS One ; 15(12): e0244712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382786

RESUMO

OBJECTIVES: To compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. METHODS: In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). RESULTS: Among DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46-2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65-1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78-14.21), ANA (OR = 14.75, 95%CI: 4.09-53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60-95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). CONCLUSIONS: Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.


Assuntos
Autoanticorpos/sangue , Síndromes do Olho Seco/sangue , Síndrome de Sjogren/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Complemento C3 , Complemento C4 , Síndromes do Olho Seco/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangue , Síndrome de Sjogren/imunologia , Adulto Jovem
9.
Int J Mol Sci ; 21(24)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322152

RESUMO

Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.


Assuntos
Autoimunidade/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Aparelho Lacrimal/imunologia , Glicoproteínas de Membrana/imunologia , Síndrome de Sjogren/imunologia , Receptor 7 Toll-Like/imunologia , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Interferon Tipo I/metabolismo , Aparelho Lacrimal/citologia , Aparelho Lacrimal/patologia , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , RNA-Seq , Glândulas Salivares/citologia , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Sexo , Receptor 7 Toll-Like/genética
10.
Molecules ; 25(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202656

RESUMO

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Betacoronavirus/patogenicidade , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/fisiopatologia , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Esquema de Medicação , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/virologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Zika virus/patogenicidade , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia
11.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 136-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093777

RESUMO

Background: Interstitial lung disease (ILD) is a common complication of primary Sjögren's syndrome (pSS). Because there is a paucity of literature on the management of pSS-associated ILD (pSS-ILD), this retrospective cohort study assessed the efficacy of azathioprine and mycophenolate therapy in adult patients with pSS-ILD. Methods: A retrospective cohort study was performed using electronic health records to identify adults meeting the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for pSS. The presence of pSS-ILD was confirmed by characteristic high-resolution computed tomography and/or histopathology findings. Sociodemographic, clinical, and pulmonary function test (PFT) data were abstracted for patients meeting the criteria and followed longitudinally from the date of their ILD diagnosis. PFT values were anchored on time of treatment start, and linear mixed-effects modeling was used to analyze changes in diffusion capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) before and after treatment initiation. Results: We identified 19 subjects who had pSS-ILD, of whom seven were treated with azathioprine and seven were treated with mycophenolate. Within the azathioprine treated group, FVC% slope change trended toward improvement from a rate of -9.8% per month pre-treatment to 2.1% per month post-treatment (p = 0.13). Within the mycophenolate treated group, FVC% slope change improved from a rate of 1.5% per month pre-treatment to 4.3% per month post-treatment (p = 0.02) and DLCO% slope changed from a rate of -3.8% to -1.3% per month (p = 0.01) after therapy start. Conclusions: Mycophenolate treatment was associated with significant improvement in PFTs of pSS-ILD patients over time, and azathioprine treatment followed a similar non-significanttrend. Additional prospective studies are needed to further evaluate these findings. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 136-147).


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pulmão/efeitos dos fármacos , Ácido Micofenólico/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Azatioprina/efeitos adversos , Registros Eletrônicos de Saúde , Feminino , Humanos , Imunossupressores/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/imunologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Fatores de Tempo , Resultado do Tratamento
12.
Mol Immunol ; 127: 107-111, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32950755

RESUMO

BACKGROUND: T helper 17 (Th17) cell responses were involved in the pathophysiology of primary Sjögren's syndrome (pSS). IL-38 has been reported to inhibit the secretion of chemokines involved in Th17 pathway. This study aimed to explore the regulation of Th17 response by IL-38 in pSS. METHODS: Twenty-four pSS patients, 15 non-pSS control, and 13 health subjects were recruited. The expression of IL-38 and Th17 cytokines were detected and compared between pSS and controls. Human peripheral blood mononuclear cells (PBMCs) and minor salivary gland mononuclear cells (MSGMs) were purified and stimulated by IL-38. The differentiation and function of Th17 cells were evaluated by PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: The pSS patients presented with significantly lower expression of IL-38 and higher Th17 cytokines (IL-17 and IL-23) compared with both non-pSS and healthy controls. The IL-38 inhibited the differentiation and function of Th17 responses from PBMCs and MSGMs. The IL-38 treatment could inhibit the Th17 response in mice model. CONCLUSIONS: IL-38 inhibits T helper 17 type responses in pSS, suggesting that IL-38 may be used as potential treatment target in pSS.


Assuntos
Interleucinas/metabolismo , Síndrome de Sjogren/imunologia , Células Th17/imunologia , Adulto , Animais , Autoanticorpos/sangue , Estudos de Casos e Controles , Diferenciação Celular , Citocinas/metabolismo , Feminino , Humanos , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucinas/genética , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Saliva/metabolismo , Glândulas Salivares/patologia , Transdução de Sinais , Síndrome de Sjogren/sangue
13.
Adv Rheumatol ; 60(1): 32, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517786

RESUMO

Hydroxychloroquine and chloroquine, also known as antimalarial drugs, are widely used in the treatment of rheumatic diseases and have recently become the focus of attention because of the ongoing COVID-19 pandemic. Rheumatologists have been using antimalarials to manage patients with chronic immune-mediated inflammatory rheumatic diseases for decades. It is an appropriate time to review their immunomodulatory and anti-inflammatory mechanisms impact on disease activity and survival of systemic lupus erythematosus patient, including antiplatelet effect, metabolic and lipid benefits. We also discuss possible adverse effects, adding a practical and comprehensive approach to monitoring rheumatic patients during treatment with these drugs.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Cloroquina/farmacologia , Hidroxicloroquina/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Infecções por Coronavirus/tratamento farmacológico , Erupção por Droga/etiologia , Interações Medicamentosas , Feminino , Glucose/metabolismo , Cardiopatias/induzido quimicamente , Humanos , Lipídeos/sangue , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pandemias , Agregação Plaquetária/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Gravidez , Insuficiência Renal/prevenção & controle , Doenças Retinianas/induzido quimicamente , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia
15.
Ann Rheum Dis ; 79(4): 518-524, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114510

RESUMO

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS: We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. RESULTS: We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. CONCLUSION: Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.


Assuntos
Linfócitos B/imunologia , Ativação Linfocitária/imunologia , NF-kappa B/imunologia , Proteínas de Neoplasias/imunologia , Síndrome de Sjogren/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Lactonas , Masculino , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa/imunologia , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Fosforilação , RNA Interferente Pequeno , Sesquiterpenos , Síndrome de Sjogren/metabolismo , Receptor Toll-Like 9/imunologia , Receptor Toll-Like 9/metabolismo , Fator de Transcrição RelA/imunologia , Fator de Transcrição RelA/metabolismo , Adulto Jovem
16.
Proc Natl Acad Sci U S A ; 117(12): 6630-6639, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32161138

RESUMO

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 ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-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.


Assuntos
Doenças Autoimunes/patologia , Galectina 1/fisiologia , Tolerância Imunológica/imunologia , Glândulas Salivares/patologia , Sialadenite/patologia , Síndrome de Sjogren/patologia , Linfócitos T Reguladores/imunologia , Adulto , Fatores Etários , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Estudos de Casos e Controles , Células Dendríticas/imunologia , Feminino , Glicosilação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Pessoa de Meia-Idade , N-Acetilglucosaminiltransferases/fisiologia , Polissacarídeos/metabolismo , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Sialadenite/imunologia , Sialadenite/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo
17.
Clin Immunol ; 214: 108384, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171889

RESUMO

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models. These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.


Assuntos
Doenças Autoimunes do Sistema Nervoso/complicações , Disfunção Cognitiva/etiologia , Síndromes da Dor Regional Complexa/etiologia , Síndrome de Fadiga Crônica/etiologia , Síndrome da Taquicardia Postural Ortostática/etiologia , Disautonomias Primárias/complicações , Próteses e Implantes/efeitos adversos , Silicones/efeitos adversos , Neuropatia de Pequenas Fibras/complicações , Especificidade de Anticorpos , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/psicologia , Doenças Autoimunes do Sistema Nervoso/terapia , Autoimunidade , Disfunção Cognitiva/imunologia , Síndromes da Dor Regional Complexa/imunologia , Síndromes da Dor Regional Complexa/psicologia , Síndromes da Dor Regional Complexa/terapia , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/psicologia , Síndrome de Fadiga Crônica/terapia , Humanos , Técnicas de Imunoadsorção , Imunoterapia , Síndrome da Taquicardia Postural Ortostática/imunologia , Síndrome da Taquicardia Postural Ortostática/psicologia , Síndrome da Taquicardia Postural Ortostática/terapia , Disautonomias Primárias/psicologia , Disautonomias Primárias/terapia , Receptores Acoplados a Proteínas-G/imunologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Neuropatia de Pequenas Fibras/psicologia , Neuropatia de Pequenas Fibras/terapia
18.
Sci Rep ; 10(1): 2967, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076051

RESUMO

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease, with only palliative treatments available. Recent work has suggested that increased bone morphogenetic protein 6 (BMP6) expression could alter cell signaling in the salivary gland (SG) and result in the associated salivary hypofunction. We examined the prevalence of elevated BMP6 expression in a large cohort of pSS patients and tested the therapeutic efficacy of BMP signaling inhibitors in two pSS animal models. Increased BMP6 expression was found in the SGs of 54% of pSS patients, and this increased expression was correlated with low unstimulated whole saliva flow rate. In mouse models of SS, inhibition of BMP6 signaling reduced phosphorylation of SMAD1/5/8 in the mouse submandibular glands, and led to a recovery of SG function and a decrease in inflammatory markers in the mice. The recovery of SG function after inhibition of BMP6 signaling suggests cellular plasticity within the salivary gland and a possibility for therapeutic intervention that can reverse the loss of function in pSS.


Assuntos
Receptores de Ativinas Tipo I/antagonistas & inibidores , Proteína Morfogenética Óssea 6/metabolismo , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Quinolinas/administração & dosagem , Glândulas Salivares/patologia , Síndrome de Sjogren/tratamento farmacológico , Receptores de Ativinas Tipo I/metabolismo , Adulto , Idoso , Animais , Proteína Morfogenética Óssea 6/análise , Proteína Morfogenética Óssea 6/genética , Linhagem Celular , Feminino , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Saliva/imunologia , Saliva/metabolismo , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/metabolismo , Glândulas Salivares/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Síndrome de Sjogren/fisiopatologia , Proteínas Smad Reguladas por Receptor/metabolismo , Adulto Jovem
19.
Int J Mol Sci ; 21(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079137

RESUMO

Autonomic neuropathy has been reported in autoimmune rheumatic diseases (ARD) including Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, the pathophysiological mechanism underlying autonomic dysfunction remains unknown to researchers. On the other hand, autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder, which causes dysautonomia that is mediated by autoantibodies against ganglionic acetylcholine receptors (gAChRs). The purpose of this review was to describe the characteristics of autonomic disturbance through previous case reports and the functional tests used in these studies and address the importance of anti-gAChR antibodies. We have established luciferase immunoprecipitation systems to detect antibodies against gAChR in the past and determined the prevalence of gAChR antibodies in various autoimmune diseases including AAG and rheumatic diseases. Autonomic dysfunction, which affects lower parasympathetic and higher sympathetic activity, is usually observed in ARD. The anti-gAChR antibodies may play a crucial role in autonomic dysfunction observed in ARD. Further studies are necessary to determine whether anti-gAChR antibody levels are correlated with the severity of autonomic dysfunction in ARD.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Gânglios Autônomos/fisiopatologia , Receptores Colinérgicos/imunologia , Doenças Reumáticas/fisiopatologia , Animais , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Sistema Nervoso Autônomo/imunologia , Sistema Nervoso Autônomo/fisiopatologia , Gânglios Autônomos/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Doenças Reumáticas/imunologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/fisiopatologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia
20.
Rheumatology (Oxford) ; 59(6): 1218-1225, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32025734

RESUMO

Sjögren's syndrome (SjS) accompanied by other systemic autoimmune rheumatic connective tissue diseases has historically been termed 'secondary' in contrast to 'primary' SjS as a standalone entity. However, it is a matter of a long-standing debate whether the prefixes 'primary' and 'secondary', including a temporal component, are obsolete in the terminology of SjS. We review the history and the pathophysiological, chronological, genetic, histological and clinical data underlying the concept of 'secondary' SjS. There are important unintended consequences of the nomenclature; notably 'secondary' SjS has been much less researched and is often excluded from clinical trials. We argue for further research, a change in terminology and more stringent classification. Further we highlight possible opportunities for trials in SjS and other systemic autoimmune diseases that might contribute to an advance in care for all patients with SjS.


Assuntos
Artrite Reumatoide/complicações , Autoimunidade , Lúpus Eritematoso Sistêmico/complicações , Escleroderma Sistêmico/complicações , Síndrome de Sjogren/complicações , Artrite Reumatoide/imunologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Escleroderma Sistêmico/imunologia , Síndrome de Sjogren/imunologia
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