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1.
Front Immunol ; 12: 705079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484201

RESUMO

Recent studies suggest that elevated CXCL13 serum levels in patients with primary Sjögren's syndrome (pSS) associate with minor salivary gland (MSG) histologic features, disease severity, as well as high-risk status for non-Hodgkin lymphoma (NHL) development and NHL itself. In contrast, limited discriminative value of CXCL13 saliva levels has been reported. Prompt by these reports, we sought to validate the clinical utility of CXCL13 by investigating potential correlations of serum and saliva levels with MSG histopathologic [including CXCL13+-cell number, severity of infiltrates and germinal center (GC) formation], serologic and clinical parameters, as well as NHL. CXCL13 levels were evaluated in paired serum and saliva specimens of 45 pSS patients (15 with NHL; pSS-associated NHL: SSL), 11 sicca-controls (sicca-complaining individuals with negative MSG biopsy and negative autoantibody profile), 10 healthy individuals (healthy-controls) and 6 non-SS-NHLs. CXCL13+-cells were measured in paired MSG-tissues of 22 of pSS patients studied (including 7 SSLs) and all sicca-controls. CXCL13 serum levels were significantly increased in pSS and SSL patients compared to sicca- and healthy-controls and were positively correlated with the CXCL13+-cell number and biopsy focus-score. Serum CXCL13 was significantly higher in pSS patients with GCs, rheumatoid factor, hypocomplementemia, high disease activity, NHL and in high-risk patients for NHL development. CXCL13 saliva levels were significantly increased in SSL patients (compared to non-SS-NHLs), patients with GCs and in high-risk for NHL patients. Univariate analysis revealed that CXCL13 serum, but not saliva, levels were associated with lymphoma, an association that did not survive multivariate analysis. Conclusively, our findings confirm that serum, but not saliva, levels of CXCL13 are associated with histologic, serologic and clinical features indicative of more severe pSS.

2.
Front Immunol ; 12: 719023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512643

RESUMO

There is strong evidence that COVID-19 pathophysiology is mainly driven by a spatiotemporal immune deregulation. Both its phenotypic heterogeneity, spanning from asymptomatic to severe disease/death, and its associated mortality, are dictated by and linked to maladaptive innate and adaptive immune responses against SARS-CoV-2, the etiologic factor of the disease. Deregulated interferon and cytokine responses, with the contribution of immune and cellular stress-response mediators (like cellular senescence or uncontrolled inflammatory cell death), result in innate and adaptive immune system malfunction, endothelial activation and inflammation (endothelitis), as well as immunothrombosis (with enhanced platelet activation, NET production/release and complement hyper-activation). All these factors play key roles in the development of severe COVID-19. Interestingly, another consequence of this immune deregulation, is the production of autoantibodies and the subsequent development of autoimmune phenomena observed in some COVID-19 patients with severe disease. These new aspects of the disease that are now emerging (like autoimmunity and cellular senescence), could offer us new opportunities in the field of disease prevention and treatment. Simultaneously, lessons already learned from the immunobiology of COVID-19 could offer new insights, not only for this disease, but also for a variety of chronic inflammatory responses observed in autoimmune and (auto)inflammatory diseases.


Assuntos
COVID-19/imunologia , SARS-CoV-2/imunologia , Humanos
3.
Cancer Genomics Proteomics ; 18(5): 605-626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34479914

RESUMO

In this review, the fundamental basis of machine learning (ML) and data mining (DM) are summarized together with the techniques for distilling knowledge from state-of-the-art omics experiments. This includes an introduction to the basic mathematical principles of unsupervised/supervised learning methods, dimensionality reduction techniques, deep neural networks architectures and the applications of these in bioinformatics. Several case studies under evaluation mainly involve next generation sequencing (NGS) experiments, like deciphering gene expression from total and single cell (scRNA-seq) analysis; for the latter, a description of all recent artificial intelligence (AI) methods for the investigation of cell sub-types, biomarkers and imputation techniques are described. Other areas of interest where various ML schemes have been investigated are for providing information regarding transcription factors (TF) binding sites, chromatin organization patterns and RNA binding proteins (RBPs), while analyses on RNA sequence and structure as well as 3D dimensional protein structure predictions with the use of ML are described. Furthermore, we summarize the recent methods of using ML in clinical oncology, when taking into consideration the current omics data with pharmacogenomics to determine personalized treatments. With this review we wish to provide the scientific community with a thorough investigation of main novel ML applications which take into consideration the latest achievements in genomics, thus, unraveling the fundamental mechanisms of biology towards the understanding and cure of diseases.

4.
Cells ; 10(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34440897

RESUMO

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren's syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto's thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.

5.
Viruses ; 13(6)2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198719

RESUMO

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using 'in-house' methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of 'non-responders' a misnomer.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Antígenos Virais/imunologia , Teste Sorológico para COVID-19/normas , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Anticorpos Antivirais/metabolismo , Antígenos Virais/metabolismo , Sítios de Ligação de Anticorpos , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste Sorológico para COVID-19/estatística & dados numéricos , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Masculino , Sensibilidade e Especificidade , Soroconversão , Adulto Jovem
6.
Front Immunol ; 12: 693911, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305928

RESUMO

Introduction: The purpose of this study was to identify differentially expressed proteins in salivary glands of the ERdj5 knockout mouse model for Sjögren's syndrome and to elucidate possible mechanisms for the morbid phenotype development. At the same time, we describe for the first time the sexual dimorphism of the murine submandibular salivary gland at the proteome level. Methods: We performed Liquid Chromatography/Mass Spectrometry in salivary gland tissues from both sexes of ERdj5 knockout and 129SV wildtype mice. The resulting list of proteins was evaluated with bioinformatic analysis and selected proteins were validated by western blot and immunohistochemistry and further analyzed at the transcription level by qRT-PCR. Results: We identified 88 deregulated proteins in females, and 55 in males in wildtype vs knockout comparisons. In both sexes, Kallikrein 1b22 was highly upregulated (fold change>25, ANOVA p<0.0001), while all other proteases of this family were either downregulated or not significantly affected by the genotype. Bioinformatic analysis revealed a possible connection with the downregulated NGF that was further validated by independent methods. Concurrently, we identified 416 proteins that were significantly different in the salivary gland proteome of wildtype female vs male mice and highlighted pathways that could be driving the strong female bias of the pathology. Conclusion: Our research provides a list of novel targets and supports the involvement of an NGF-mediating proteolytic deregulation pathway as a focus point towards the better understanding of the underlying mechanism of Sjögren's syndrome.

7.
J Autoimmun ; 123: 102687, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311142

RESUMO

The impact of SARS-CoV-2 infection in patients with autoimmune/auto-inflammatory rheumatic diseases (AARD) under immunomodulatory treatment has been a focus of interest during the COVID-19 pandemic. In this observational study, demographic data, disease related features and comorbidities, COVID-19 manifestations and outcome as well as antibody responses to SARS-CoV-2 were recorded among 77 consecutive patients with underlying AARD infected by SARS-CoV-2. Analysis of data was performed using univariate and multivariate models. Most patients (68.8%) had a mild COVID-19 course. The predominant clinical manifestations were fatigue (58.4%), low grade fever (45.4%) and upper respiratory tract symptoms (68.8%). About a quarter of patients required hospitalization (23.3%) and the mortality rate was 1.3%. Regarding COVID-19 severity, prior treatment with corticosteroids, mycophenolate mofetil or rituximab was more common in patients who developed a more serious disease course (60.0 vs 29.9%, p = 0.003, 40.0 vs 7.5%, p = 0.003, 10.0 vs 0.0%, p = 0.009, respectively). When disease related features and comorbidities were considered in multivariate models, older age and lung disease in the context of the AARD were found to be independent predictive factors for hospitalization (OR [95%]: 1.09 [1.03-1.15] and 6.43 [1.11-37.19]). Among COVID-19 related features, patients with shortness of breath and high-grade fever were more likely to get hospitalized (OR [95%]: 7.06 [1.36-36.57], 12.04 [2.96-48.86]), while anosmia was independently associated with lower hospitalization risk (OR [95%]: 0.09 [0.01-0.99]). Though the majority of AARD patients displayed a mild COVID-19 course, certain underlying disease features and COVID-19 related manifestations should prompt alertness for the physician to identify patients with AARD at high risk for severe COVID-19 and need for hospitalization.


Assuntos
Doenças Autoimunes/epidemiologia , COVID-19/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Comorbidade , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/imunologia , Estado Terminal , Feminino , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hipotireoidismo/epidemiologia , Hospedeiro Imunocomprometido , Imunoglobulina G/biossíntese , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Literatura de Revisão como Assunto , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Avaliação de Sintomas
8.
Artigo em Inglês | MEDLINE | ID: mdl-34260696

RESUMO

OBJECTIVES: To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with giant cell arteritis (GCA). METHODS: Ten patients with GCA [5 with limited and 5 with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose (FDG) positron-emission tomography with computed tomography (PET/CT)] and 8 with polymyalgia rheumatica (PMR) were studied. The presence, location, quantitation, and decoration of NETs with IL-6, IL-1ß, and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients. RESULTS: All temporal artery biopsies from GCA, but not PMR patients, had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were -PET/CT(+) and 3 PET/CT(-) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1ß(+)NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A. CONCLUSIONS: NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centers will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.

9.
Front Immunol ; 12: 683623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220834

RESUMO

Background: B-cell non-Hodgkin's lymphoma (B-NHL) is one of the major complications of primary Sjögren's syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)-a product mainly of tissue macrophages-is found in the circulation associated with lipoproteins and has been previously involved in cardiovascular, autoimmune, and malignant diseases, including lymphoma. Objective: The purpose of the current study was to investigate the contributory role of Lp-PLA2 in B-NHL development in the setting of primary SS. Methods: Lp-PLA2 activity in serum samples collected from 50 primary SS patients with no lymphoma (SS-nL), 9 primary SS patients with lymphoma (SS-L), and 42 healthy controls (HC) was determined by detection of [3H]PAF degradation products by liquid scintillation counter. Moreover, additional sera from 50 SS-nL, 28 SS-L, and 32 HC were tested for Lp-PLA2 activity using a commercially available ELISA kit. Lp-PLA2 mRNA, and protein expression in minor salivary gland (MSG) tissue samples derived from SS-nL, SS-L patients, and sicca controls (SC) were analyzed by real-time PCR, Western blot, and immunohistochemistry. Results: Serum Lp-PLA2 activity was significantly increased in SS-L compared to both SS-nL and HC by two independent methods implemented [mean ± SD (nmol/min/ml): 62.0 ± 13.4 vs 47.6 ± 14.4 vs 50.7 ± 16.6, p-values: 0.003 and 0.04, respectively, and 19.4 ± 4.5 vs 15.2 ± 3.3 vs 14.5 ± 3.0, p-values: <0.0001, in both comparisons]. ROC analysis revealed that the serum Lp-PLA2 activity measured either by radioimmunoassay or ELISA has the potential to distinguish between SS-L and SS-nL patients (area under the curve [AUC]: 0.8022, CI [95%]: 0.64-0.96, p-value: 0.004 for radioimmunoassay, and AUC: 0.7696, CI [95%]: 0.66-0.88, p-value: <0.0001, for ELISA). Lp-PLA2 expression in MSG tissues was also increased in SS-L compared to SS-nL and SC at both mRNA and protein level. ROC analysis revealed that both MSG mRNA and protein Lp-PLA2 have the potential to distinguish between SS-nL and SS-L patients (area under the curve [AUC] values of 0.8490, CI [95%]: 0.71-0.99, p-value: 0.0019 and 0.9444, CI [95%]: 0.79-1.00, p- value: 0.0389 respectively). No significant difference in either serum Lp-PLA2 activity or MSG tissue expression was observed between SS-nL and HC. Conclusions: Lp-PLA2 serum activity and MSG tissue mRNA/protein expression could be a new biomarker and possibly a novel therapeutic target for B-cell lymphoproliferation in the setting of SS.

10.
Comput Biol Med ; 134: 104520, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34118751

RESUMO

Virtual population generation is an emerging field in data science with numerous applications in healthcare towards the augmentation of clinical research databases with significant lack of population size. However, the impact of data augmentation on the development of AI (artificial intelligence) models to address clinical unmet needs has not yet been investigated. In this work, we assess whether the aggregation of real with virtual patient data can improve the performance of the existing risk stratification and disease classification models in two rare clinical domains, namely the primary Sjögren's Syndrome (pSS) and the hypertrophic cardiomyopathy (HCM), for the first time in the literature. To do so, multivariate approaches, such as, the multivariate normal distribution (MVND), and straightforward ones, such as, the Bayesian networks, the artificial neural networks (ANNs), and the tree ensembles are compared against their performance towards the generation of high-quality virtual data. Both boosting and bagging algorithms, such as, the Gradient boosting trees (XGBoost), the AdaBoost and the Random Forests (RFs) were trained on the augmented data to evaluate the performance improvement for lymphoma classification and HCM risk stratification. Our results revealed the favorable performance of the tree ensemble generators, in both domains, yielding virtual data with goodness-of-fit 0.021 and KL-divergence 0.029 in pSS and 0.029, 0.027 in HCM, respectively. The application of the XGBoost on the augmented data revealed an increase by 10.9% in accuracy, 10.7% in sensitivity, 11.5% in specificity for lymphoma classification and 16.1% in accuracy, 16.9% in sensitivity, 13.7% in specificity in HCM risk stratification.


Assuntos
Algoritmos , Inteligência Artificial , Teorema de Bayes , Humanos , Redes Neurais de Computação , Medição de Risco
11.
J Autoimmun ; 121: 102648, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34029875

RESUMO

The aim of this study is to explore the role of labial minor salivary gland (LMSG) focus score (FS) in stratifying Sjögren's Syndrome (SS) patients, lymphoma development prediction and to facilitate early lymphoma diagnosis. Ιn an integrated cohort of 1997 patients, 618 patients with FS ≥ 1 and at least one-year elapsing time interval from SS diagnosis to lymphoma diagnosis or last follow up were identified. Clinical, laboratory and serological features were recorded. A data driven logistic regression model was applied to identify independent lymphoma associated risk factors. Furthermore, a FS threshold maximizing the difference of time interval from SS until lymphoma diagnosis between high and low FS lymphoma subgroups was investigated, to develop a follow up strategy for early lymphoma diagnosis. Of the 618 patients, 560 were non-lymphoma SS patients while the other 58 had SS and lymphoma. FS, cryoglobulinemia and salivary gland enlargement (SGE) were proven to be independent lymphoma associated risk factors. Lymphoma patients with FS ≥ 4 had a statistically significant shorter time interval from SS to lymphoma diagnosis, compared to those with FS < 4 (4 vs 9 years, respectively, p = 0,008). SS patients with FS ≥ 4 had more frequently B cell originated manifestations and lymphoma, while in patients with FS < 4, autoimmune thyroiditis was more prevalent. In the latter group SGE was the only lymphoma independent risk factor. A second LMSG biopsy is patients with a FS ≥ 4, 4 years after SS diagnosis and in those with FS < 4 and a history of SGE, at 9-years, may contribute to an early lymphoma diagnosis. Based on our results we conclude that LMSG FS, evaluated at the time of SS diagnosis, is an independent lymphoma associated risk factor and may serve as a predictive biomarker for the early diagnosis of SS-associated lymphomas.

13.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33921064

RESUMO

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem (HSCs) and/or progenitor cells disorders. The established dependence of MDS progenitors on the hypoxic bone marrow (BM) microenvironment turned scientific interests to the transcription factor hypoxia-inducible factor 1 (HIF-1). HIF-1 facilitates quiescence maintenance and regulates differentiation by manipulating HSCs metabolism, being thus an appealing research target. Therefore, we examine the aberrant HIF-1 stabilization in BMs from MDS patients and controls (CTRLs). Using a nitroimidazole-indocyanine conjugate, we show that HIF-1 aberrant expression and transcription activity is oxygen independent, establishing the phenomenon of pseudohypoxia in MDS BM. Next, we examine mitochondrial quality and quantity along with levels of autophagy in the differentiating myeloid lineage isolated from fresh BM MDS and CTRL aspirates given that both phenomena are HIF-1 dependent. We show that the mitophagy of abnormal mitochondria and autophagic death are prominently featured in the MDS myeloid lineage, their severity increasing with intra-BM blast counts. Finally, we use in vitro cultured CD34+ HSCs isolated from fresh human BM aspirates to manipulate HIF-1 expression and examine its potential as a therapeutic target. We find that despite being cultured under 21% FiO2, HIF-1 remained aberrantly stable in all MDS cultures. Inhibition of the HIF-1α subunit had a variable beneficial effect in all <5%-intra-BM blasts-MDS, while it had no effect in CTRLs or in ≥5%-intra-BM blasts-MDS that uniformly died within 3 days of culture. We conclude that HIF-1 and pseudohypoxia are prominently featured in MDS pathobiology, and their manipulation has some potential in the therapeutics of benign MDS.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , Autofagia/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitofagia/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Células Mieloides/ultraestrutura , Nitroimidazóis/farmacologia , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
Vaccine ; 39(11): 1593-1597, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33610375

RESUMO

INTRODUCTION: Patients with autoimmune rheumatic diseases (ARDs) are at increased risk for pneumococcal infections and should be vaccinated against Streptococcus pneumoniae. Data on the rates of pneumococcal vaccination among patients with ARDs in Southern Europe are scarce. Here, we estimate the pneumococcal vaccination rate in patients living in Greece with ARDs, explore the patients' awareness regarding vaccination, and try to recognize factors that influence the vaccine uptake. METHODS: Between October 2015 and September 2016, a structured questionnaire was provided to all consecutive patients with ARDs attending one outpatient clinic of our department. The survey included parameters concerning patients' demographics, underlying ARD and immunosuppressive medications, other comorbidities, vaccine type, knowledge about infection risk and necessity of vaccination. Univariate and multivariate analyses were performed to study any association of these factors with the vaccination uptake. RESULTS: Overall, 395 patients with ARDs (30.13% aged >65 years and 78.99% female) participated in our survey. The most frequent ARD was rheumatoid arthritis (43.04%); 40.51% of patients were receiving biologic agents and 44.56% steroids. Pneumococcal vaccination rate was 49.37%, while 45.06% of patients have been vaccinated during the last five years and only 8.21% of them had a second pneumococcal vaccine, as per national guidelines. The decision of vaccination was significantly influenced by the patient's age (>65 years) (p < 0.001) and the complete awareness of reasons for being vaccinated (p < 0.001), but not by presence of comorbidities, the type of ARD or administration of a biologic agent. The main reason for no vaccination was that it was not suggested by the caring physician (82.50%). CONCLUSIONS: In our cohort of patients with ARDs the pneumococcal vaccination was suboptimal. Better understanding of the significance of vaccination by the patient and suggestion for vaccination by the caring physician will improve vaccination uptake and optimize the clinical benefits among patients with ARDs.


Assuntos
Vacinas contra Influenza , Infecções Pneumocócicas , Idoso , Auditoria Clínica , Europa (Continente) , Feminino , Grécia/epidemiologia , Humanos , Masculino , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Vacinação
15.
Drugs Aging ; 38(4): 265-284, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33619703

RESUMO

Primary Sjögren's syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60 years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65 years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the recently published 2020 European League Against Rheumatism (EULAR) recommendations for the management of the disease with topical and systemic therapies. These recommendations are applicable to all patients with primary SjS regardless of age at diagnosis, although the therapeutic management in older patients requires additional considerations. Older patients are more likely to have pulmonary, liver, kidney, or heart-related comorbidities (even cognitive disturbances); caution is required when most drugs are used, including muscarinic agents, systemic corticosteroids and synthetic immunosuppressants. It is also important to monitor the use of eye drops containing steroids due to the increased risk of developing cataracts, a frequent ocular complication in the older population. In contrast, the majority of drugs that can be used topically (pilocarpine rinses, eye drops containing topical non-steroidal anti-inflammatory drugs (NSAIDs) or cyclosporine A, topical dermal formulations of NSAIDs) have shown an acceptable safety profile in older patients, as well as rituximab. A rigorous evaluation of the medical history of older patients is essential when drugs included in the EULAR guidelines are prescribed, with special attention to factors frequently related to ageing, such as polypharmacy, the existence of organ-specific comorbidities, or the enhanced susceptibility to infections.

16.
Expert Rev Clin Immunol ; 17(2): 127-141, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33478279

RESUMO

Introduction: Sjögren's syndrome is a unique systemic autoimmune disease, placed in the center of systemic autoimmunity and at the crossroads of autoimmunity and lymphoproliferation. The diverse clinical picture of the disease, the inefficacy of current biologic treatments, and the co-existence with lymphoma conferring to the patients' morbidity and mortality force the scientific community to review disease pathogenesis and reveal the major implicated cellular and molecular elements.Areas covered: Biomarkers for early diagnosis, prediction, stratification, monitoring, and targeted treatments can serve as a tool to interlink and switch from the clinical phenotyping of the disease into a more sophisticated classification based on the underlying critical molecular pathways and endotypes. Such a transition may define the establishment of the so-called precision medicine era in which patients' management will be based on grouping according to pathogenetically related biomarkers. In the current work, literature on Sjogren's syndrome covering several research fields including clinical, translational, and basic research has been reviewed.Expert opinion: The perspectives of clinical and translational research are anticipated to define phenotypic clustering of high-risk pSS patients and link the clinical picture of the disease with fundamental molecular mechanisms and molecules implicated in pathogenesis.

17.
Autoimmun Rev ; 20(2): 102742, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33333235

RESUMO

Autoimmune rheumatic diseases (ARD) are characterized by systemic manifestations and multiple organ involvement, including the lung. Interstitial Lung Disease (ILD) is a cardinal manifestation of lung involvement in patients with ARD and is associated with significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are used as first -line treatment. Targeted therapies, such as biological disease modifying antirheumatic drugs (DMARDS) and anti- fibrotic agents are new treatment options. In this review we discuss the role of targeted therapies in patients with ILD secondary to ARD.


Assuntos
Antirreumáticos , Doenças Autoimunes , Doenças Pulmonares Intersticiais , Doenças Reumáticas , Antirreumáticos/uso terapêutico , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico
18.
Cancers (Basel) ; 12(12)2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33255926

RESUMO

Myelodysplastic syndromes (MDS) encompass a very heterogeneous group of clonal hematopoietic stem cell differentiation disorders with malignant potential and an elusive pathobiology. Given the central role of metabolism in effective differentiation, we performed an untargeted metabolomic analysis of differentiating myeloid lineage cells from MDS bone marrow aspirates that exhibited <5% (G1) or ≥5% (G2) blasts, in order to delineate its role in MDS severity and malignant potential. Bone marrow aspirates were collected from 14 previously untreated MDS patients (G1, n = 10 and G2, n = 4) and age matched controls (n = 5). Following myeloid lineage cell isolation, untargeted mass spectrometry-based metabolomics analysis was performed. Data were processed and analyzed using Metabokit. Enrichment analysis was performed using Metaboanalyst v4 employing pathway-associated metabolite sets. We established a bioenergetic profile coordinated by the Warburg phenomenon in both groups, but with a massively different outcome that mainly depended upon its group mitochondrial function and redox state. G1 cells are overwhelmed by glycolytic intermediate accumulation due to failing mitochondria, while the functional electron transport chain and improved redox in G2 compensate for Warburg disruption. Both metabolomes reveal the production and abundance of epigenetic modifiers. G1 and G2 metabolomes differ and eventually determine the MDS clinical phenotype, as well as the potential for malignant transformation.

19.
Cureus ; 12(10): e10766, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33154839

RESUMO

A nine-year-old girl with a two-month history of fever and generalized malaise, along with intermittent abdominal pain, immigrant myalgia, throat pain, anorexia, and long-standing failure to thrive, was admitted to our department for further investigation and treatment. Detailed medical history revealed recurrent inflammation attacks from a very young age and a heavily burdened family history. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was highly suspected. Genetic screening was performed and several members of the family were found to be carriers of C73Y mutation in exon 3, which is a novel tumor necrosis factor superfamily receptor 1A (TNFRSF1A) mutation. The girl was treated with an interleukin-1ß inhibitor, canakinumab, which induced immediate and complete remission of disease that interestingly lasted for a long period even after medication discontinuation.

20.
Front Immunol ; 11: 594096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193443

RESUMO

Objectives: To study the clinical, serological and histologic features of primary Sjögren's syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development. Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups. Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11-3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34-8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years. Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.


Assuntos
Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/etiologia , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Humanos , Linfoma/epidemiologia , Linfoma/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Prevalência , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Adulto Jovem
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