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1.
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
2.
J Autoimmun ; 121: 102648, 2021 Jul.
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.

3.
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
4.
Clin Med (Lond) ; 20(5): e206-e208, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32934067

RESUMO

A 42-year-old man presented with fever, sore throat, rash and painful right knee swelling, preceded by self-medication with oral steroids. Blood and knee cultures yielded group A Streptococcus After 2 weeks of intravenous antibiotics and two arthroscopic knee debridements, he continued to experience spiking fevers, and electrocardiographic changes developed. We postulate that the patient suffered from the first presentation of acute rheumatic fever, following an invasive group A bacteraemic streptococcal infection. The possible role of cardiac magnetic resonance imaging in the diagnosis of rheumatic carditis is discussed.


Assuntos
Miocardite , Febre Reumática , Infecções Estreptocócicas , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Miocardite/diagnóstico por imagem , Febre Reumática/complicações , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/diagnóstico por imagem , Streptococcus pyogenes
5.
J Clin Med ; 9(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806710

RESUMO

BACKGROUND: To compare the clinical, serological and histologic features between male and female patients with Sjögren's syndrome (SS) and explore the potential effect of gender on lymphoma development. METHODS: From a multicenter population (Universities of Udine, Pisa and Athens, Harokopion and Ioannina (UPAHI)) consisting of consecutive SS patients fulfilling the 2016 ACR/EULAR criteria, male patients were identified, matched and compared with female controls. Data-driven multivariable logistic regression analysis was applied to identify independent lymphoma-associated factors. RESULTS: From 1987 consecutive SS patients, 96 males and 192 matched female controls were identified and compared. Males had a higher frequency of lymphoma compared to females (18% vs. 5.2%, OR = 3.89, 95% CI: 1.66 to 8.67; p = 0.0014) and an increased prevalence of serum anti-La/SSB antibodies (50% vs. 34%, OR = 1.953, 95% CI: 1.19 to 3.25; p = 0.0128). No differences were observed in the frequencies of lymphoma predictors between the two genders. Data-driven multivariable logistic regression analysis revealed negative association of the female gender with lymphoma and positive association with lymphadenopathy. CONCLUSION: Male SS patients carry an increased risk of lymphoma development. Although statistics showed no difference in classical lymphoma predictors compared to females, data-driven analysis revealed gender and lymphadenopathy as independent lymphoma-associated features.

6.
Clin Exp Rheumatol ; 38 Suppl 126(4): 134-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32083547

RESUMO

OBJECTIVES: This study aims to characterise the clinical phenotype and autoantibody associations in an autoimmune population positive for anti-Ro52 and/or anti-Ro60 autoantibodies. METHODS: The sera of 508 individuals tested for autoantibody presence were found positive for anti-Ro52 and/or anti-Ro60. Medical records were available for 272 of them. Correlations of clinical, laboratory and other autoantibodies as well as disease phenotypes with the presence of anti-Ro52 and/or anti-Ro60 reactivity were examined. RESULTS: Combined serum anti-Ro52/anti-Ro60 reactivity was the most frequent one, mostly seen in Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) patients. In these patients this reactivity strongly associated with anti-La and/or anti-dsDNA autoantibodies. SS patients with combined anti-Ro52/anti-Ro60 and anti-La reactivity had clinical and/or laboratory risk factors for lymphoma development. Solo anti-Ro52 reactivity was primarily found in idiopathic inflammatory myopathies (IIM), primary biliary cholangitis (PBC), rheumatoid arthritis (RA) and SS patients. Solo anti-Ro52 also associated with anti-Jo1 and anti-M2 autoantibodies and with interstitial lung disease (ILD) in a context of IIM-related lung injury. ILD patients with combined anti-Ro52/anti-Ro-60 reactivity were diagnosed mostly as RA and/or SS. Solo anti-Ro60 reactivity strongly correlated with oral ulcers and co-existed with autoantibodies to Sm and nRNP/Sm. CONCLUSIONS: Testing for autoantibodies against both Ro peptides may guide diagnosis, classify clinical manifestations in disease entities and define prognosis in certain autoimmune disorders. A distinct weight could be given to the isolated anti-Ro specificities in the SS classification criteria.


Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Autoanticorpos , Autoantígenos , Humanos , Ribonucleoproteínas , Síndrome de Sjogren/diagnóstico
8.
J Autoimmun ; 104: 102335, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31540861

RESUMO

It is well established that distinct cell metabolic alterations strongly contribute to the modulation of innate and adaptive immune responses. In the past decade the term immunometabolism has been introduced to describe the intracellular metabolic shifts of immune cells that lead to alterations of their functions. The pathogenesis of Sjögren's syndrome (SS), also referred to as autoimmune epithelitis, is not completely understood, but strong evidence supports the central role of the salivary glandular epithelial cells which are the target cells in the initiation of the autoimmune responses. Moreover, the altered epithelial functional phenotype, observed in the salivary gland lesion, may explain their disturbed secretory as well as immunoregulatory functions. From an immunometabolic perspective we have focused our studies on the endoplasmic reticulum (ER) of the salivary gland epithelial cells (SGEC) and the implication of its altered functions in the immunogenicity of these cells in SS. We showed that ER of SGEC in SS patients in situ is stressed and extensively dilated. Using salivary gland cell cultures, we studied in vitro the effect of ER stress on the metabolic behavior and viability of the cells. ER stress induced by thapsigargin increased spliced X-box binding protein-1 (XBP-1, transcription factor that increases the transcription of UPR target genes) levels in a time-dependent manner followed by autophagy and resulted to cell apoptosis. In apoptotic cells, we observed that the autoantigens Ro52 and La were redistributed in apoptotic blebs. During the induction of ER stress autophagy rescued the cells from apoptosis acting as a protective mechanism. We have also shown that adiponectin, a multifunctional hormone, is upregulated in the SGEC of SS patients acting in an autocrine or paracrine manner in the same cells. Adiponectin through activation of AMPK, the major sensor for cell energy demands, protected SGEC from apoptosis. Our results in combination with the work of others indicate that any effort of cell adaptation to ER stress may up regulate a proinflammatory milieu. This enhances the notion that metabolic alterations of the targeted epithelial cells in SS, independently of the cause, may induce an immunogenic phenotype. Therefore, SGEC have the potential to directly regulate susceptibility to and/or severity of autoimmune responses. Since adiponectin plays a vital role in the viability of SGEC through phosphorylation of AMPK, therapeutic interventions using PPAR agonists that upregulate adiponectin and concomitantly modify the energy metabolism, may be promising candidates for therapeutic intervention in SS.


Assuntos
Apoptose/imunologia , Estresse do Retículo Endoplasmático/imunologia , Células Epiteliais , Regulação da Expressão Gênica/imunologia , Glândulas Salivares , Síndrome de Sjogren , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Glândulas Salivares/imunologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia
9.
Clin Exp Rheumatol ; 37 Suppl 118(3): 90-96, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31287405

RESUMO

OBJECTIVES: To address the need for automatically assessing the quality of clinical data in terms of accuracy, relevance, conformity, and completeness, through the concise development and application of an automated method which is able to automatically detect problematic fields and match clinical terms under a specific domain. METHODS: The proposed methodology involves the automated construction of three diagnostic reports that summarise valuable information regarding the types and ranges of each term in the dataset, along with the detected outliers, inconsistencies, and missing values, followed by a set of clinically relevant terms based on a reference model which serves as a set of terms which describes the domain knowledge of a disease of interest. RESULTS: A case study was conducted using anonymised data from 250 patients who were diagnosed with primary Sjögren's syndrome (pSS), yielding reliable outcomes that were highlighted for clinical evaluation. Our method was able to successfully identify 28 features with detected outliers, and unknown data types, as well as, identify outliers, missing values, similar terms, and inconsistencies within the dataset. The data standardisation method was able to match 76 out of 85 (89.41%) pSS-related terms according to a standard pSS reference model which has been introduced by the clinicians. CONCLUSIONS: Our results confirm the clinical value of the data curation method towards the improvement of the dataset quality through the precise identification of outliers, missing values, inconsistencies, and similar terms, as well as, through the automated detection of pSS-related relevant terms towards data standardisation.


Assuntos
Curadoria de Dados , Síndrome de Sjogren , Confiabilidade dos Dados , Humanos
12.
Clin Rheumatol ; 38(1): 125-132, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30145635

RESUMO

Myositis-specific (MSAs) or-associated autoantibodies (MAAs) have been linked to particular clinical phenotypes of idiopathic inflammatory myopathies (IIM) and appear to aid diagnosis. The objective of this study was to analyze the prevalence of MSAs and MAAs and their possible clinical associations in Greek IIM patients. This study comprised 95 IIM patients classified based on the 2017 EULAR/ACR classification criteria. All patients had MSAs and MAAs measured in their sera by line immunoblot assay. Dermatomyositis was the most prevalent IIM clinical subtype. MSAs were found in 44% of the patients, whereas MAAs in 23%. The most frequently detected MSA was anti-Jo-1 (22%), while the most frequently detected MAA was anti-Ro-52 (30%). The distributions of MSAs/MAAs did not differ between the five IIM subgroups, except for anti-Mi-2 which was only detected in dermatomyositis patients. Patients with at least one MSA and/or MAA positivity showed more frequently IIM characteristic skin rashes, while those presenting solely MAA positivity had more often puffy hands and Raynaud's phenomenon. Anti-Jo1-positive patients presented more frequently lung disease, while anti-Ro52 positivity related to mechanic's hands. Anti-Ro-52 and anti-Jo-1 strongly associated with one another. Prevalence of IIM subtypes and of MSAs/MAAs in our patients is in line with published reports in populations of similar geographic distribution. While MSA and/or MAA positivity did associate with particular clinical manifestations, it did not predict in our cohort specific IIM subgroup as defined by the latest EULAR/ACR classification criteria. Future studies are warranted to conclusively decide if these autoantibodies, measured with a standardized method, should or not be incorporated in every day clinical practice to aid IIM diagnosis.


Assuntos
Autoanticorpos/sangue , Miosite/imunologia , Adolescente , Adulto , Idoso , Autoanticorpos/classificação , Autoantígenos/imunologia , Biomarcadores/sangue , Estudos de Coortes , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Adulto Jovem
15.
J Rheumatol ; 45(6): 785-794, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29606666

RESUMO

OBJECTIVE: To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention. METHODS: Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004-2014 were analyzed. Kaplan-Meier curves and Cox regression models were used. RESULTS: Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26-0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24-0.50 for 28-joint Disease Activity Score remission). CONCLUSION: The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Espondilartrite/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
16.
FEBS Lett ; 592(1): 5-14, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29223133

RESUMO

A large body of clinical evidence on the association between stressful life events and autoimmune diseases suggests that stress may play an important role in the pathogenesis of these disorders. In this article, we discuss the effects of stress, not on the immune system but on specific cell populations against which the autoimmune reactivity is directed. Using Sjögren's syndrome as a model autoimmune disease, we review the role of stress in the initiation and perpetuation of autoimmune reactivity. We present data that reveal the effects of stress on salivary gland epithelial cells, suggesting that stress can become immunogenic through its various effects on salivary gland epithelium.


Assuntos
Autoimunidade , Síndrome de Sjogren/etiologia , Síndrome de Sjogren/imunologia , Apoptose , Sistema Nervoso Autônomo/imunologia , Autofagia , Estresse do Retículo Endoplasmático , Células Epiteliais/imunologia , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Modelos Imunológicos , Sistema Hipófise-Suprarrenal/imunologia , Glândulas Salivares/imunologia , Estresse Fisiológico
19.
Clin Exp Rheumatol ; 34(6): 999-1005, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27749220

RESUMO

OBJECTIVES: To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. METHODS: Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. RESULTS: We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). CONCLUSIONS: In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Fatores Etários , Idoso , Artrite Reumatoide/diagnóstico , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Índice de Gravidade de Doença , Resultado do Tratamento
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