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1.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

4.
Arthritis Rheumatol ; 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455077

RESUMO

OBJECTIVES: Latino patients are overrepresented among cases of coronavirus disease 2019 (COVID-19) and are at an increased risk for severe disease. Prevalence of COVID-19 in Latinos with rheumatic diseases are poorly reported. The purpose of this study was to characterize COVID-19 clinical features and outcomes in Latino patients with rheumatic diseases. METHODS: This is a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1 to October 15, 2020 were analyzed in this study. We reviewed demographics, body mass index (BMI), comorbidities, and immunomodulatory therapies. An exploratory Classification and Regression Tree (CART) analysis along with logistic regression (LR) analyses were performed to identify risk factors for COVID-19 and rheumatic disease flare. RESULTS: Out of 178 patients, 32 (18%) were identified with COVID-19 and the incidence rate of infection was found to be three-fold higher than the general Latino population. No patients required ICU level care. CART analysis and multivariable LR analysis identified BMI>30.35 as a risk factor for COVID-19 [P=0.004, OR=3.37, 95%CI (1.5-7.7)]. COVID-19 positivity was a risk factor for rheumatic disease flare [P=0.02, OR=4.57, 95%CI (1.2-17.4)]. CONCLUSION: Latino patients with rheumatic diseases had a higher rate of COVID-19 compared with the general Latino population. Obesity was identified as a risk factor for COVID-19 and COVID-19 itself was found to be a risk factor for rheumatic disease flare. Latino patients with risk factors should be followed closely, especially post-COVID-19 in anticipation of disease flare.

5.
medRxiv ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33184616

RESUMO

Objectives: Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients. Methods: Patients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry. Results: Ten SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation. None of the other SLE samples blocked IFNα signaling. Conclusions: We noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.

6.
Arthritis Rheumatol ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892506

RESUMO

We read with interest the article by Orange et al. (1) assessing whether histologic parameters of synovium were related to symptoms of rheumatoid arthritis (RA). The authors analyzed synovial tissue samples of 176 RA patients who underwent hip or knee arthroplasty. The detection of neutrophils and fibrin in synovial tissue was associated with patient-reported morning stiffness of >1 hour. They suggested that ongoing neutrophil recruitment in synovial tissue may be associated with prolonged morning stiffness.

7.
Ann Rheum Dis ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988843

RESUMO

OBJECTIVES: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE. METHODS: Proteomic/phosphoproteomic analyses were performed in healthy control (HC) normal density neutrophils (NDNs), SLE NDNs and autologous SLE LDGs. The biophysical properties of these neutrophil subsets were analysed by real-time deformability cytometry and lattice light-sheet microscopy. A two-dimensional endothelial flow system and a three-dimensional microfluidic microvasculature mimetic (MMM) were used to decouple the contributions of cell surface mediators and biophysical properties to neutrophil trafficking, respectively. RESULTS: Proteomic and phosphoproteomic differences were detected between HC and SLE neutrophils and between SLE NDNs and LDGs. Increased abundance of type 1 interferon-regulated proteins and differential phosphorylation of proteins associated with cytoskeletal organisation were identified in SLE LDGs relative to SLE NDNs. The cell surface of SLE LDGs was rougher than in SLE and HC NDNs, suggesting membrane perturbances. While SLE LDGs did not display increased binding to endothelial cells in the two-dimensional assay, they were increasingly retained/trapped in the narrow channels of the lung MMM. CONCLUSIONS: Modulation of the neutrophil proteome and distinct changes in biophysical properties are observed alongside differences in neutrophil trafficking. SLE LDGs may be increasingly retained in microvasculature networks, which has important pathogenic implications in the context of lupus organ damage and small vessel vasculopathy.

8.
Ann Rheum Dis ; 79(10): 1333-1339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32816709

RESUMO

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Seleção de Pacientes , Sensibilidade e Especificidade
10.
Proc Natl Acad Sci U S A ; 117(28): 16481-16491, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601182

RESUMO

Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.


Assuntos
Interferon Tipo I/imunologia , Neutrófilos/imunologia , Adulto , Feminino , Humanos , Imunidade Inata , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/imunologia , Síndrome de Klinefelter/metabolismo , Masculino , Fatores Sexuais , Adulto Jovem
11.
Sci Rep ; 10(1): 4462, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157125

RESUMO

Type I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNApos SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Autoanticorpos/sangue , Biomarcadores/sangue , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Proteoma/análise , Perfilação da Expressão Gênica , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Índice de Gravidade de Doença
12.
PLoS One ; 15(3): e0229184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182251

RESUMO

Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients' blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients.


Assuntos
Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Receptores Depuradores Classe E/fisiologia , Adulto , Aterosclerose/sangue , Aterosclerose/complicações , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Receptores Depuradores Classe E/sangue , Adulto Jovem
13.
JAMA Netw Open ; 3(2): e200032, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32101306

RESUMO

Importance: Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for an ever-increasing number of cancers. However, their use has also led to the emergence of immune-related adverse events, such as ICI-induced inflammatory arthritis. A reproducible, reliable, and accessible modality is needed to assess and distinguish early ICI-induced inflammatory arthritis and help in management. Magnetic resonance imaging (MRI) of joints may be helpful for early diagnosis, guiding therapeutic decision-making, and identifying patients at high risk for erosive disease. Objective: To assess the role of MRI of joints in patients with ICI-induced inflammatory arthritis. Design, Setting, and Participants: This retrospective case series included patients enrolled at the National Institutes of Health Clinical Center in Bethesda, Maryland. Patients were evaluated by the rheumatology consultation service between December 27, 2016, and May 28, 2019. A retrospective health record review was performed to determine demographic characteristics, clinical characteristics of inflammatory arthritis and malignant tumors, and imaging findings. Inclusion criteria were patients who were enrolled on various institutional review board-approved protocols of ICIs, developed joint-related symptoms, and had MRI data for at least 1 joint. Data were analyzed from June 1, 2019, to September 1, 2019. Exposures: Undergoing MRI of at least 1 joint. Main Outcomes and Measures: All MRIs were reviewed for synovitis, tenosynovitis, bone marrow edema, and soft tissue conditions. Results: A total of 8 patients (mean [SD] age, 58.8 [5.2] years; 6 women and 2 men) between the ages of 50 and 65 years who were undergoing ICI therapy for a variety of malignant tumors were included in this study. Only 1 patient was receiving combined ICI therapy. The results of 13 separate MRI examinations were reviewed. The most commonly performed MRIs were of the hands and wrists (9 MRIs), followed by knee examinations (3 MRIs). Tenosynovitis and synovitis were frequently seen in the hands and wrists. Bone marrow edema and erosions were also found in 3 patients, suggesting early damage. In larger joints (ie, knees and ankles), joint effusions and synovial thickening were characteristic. Most patients (5 patients) were treated with corticosteroids and had good responses. In patients with high-risk features on MRI imaging (eg, bone marrow edema, erosions), disease-modifying antirheumatic drug therapy was also discussed as a treatment option. Conclusions and Relevance: These findings suggest that advanced imaging may help to distinguish ICI-induced inflammatory arthritis from other causes of joint pain, aid in identifying patients at increased risk of joint damage, and provide utility in monitoring inflammatory arthritis treatment response in patients receiving ICI therapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Artrite Reumatoide/diagnóstico , Imunoterapia/efeitos adversos , Articulações/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Idoso , Artrite Reumatoide/induzido quimicamente , Diagnóstico Precoce , Feminino , Humanos , Articulações/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Clin Rheumatol ; 39(3): 681-687, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31848913

RESUMO

INTRODUCTION: Pakistan has a population of over 200 million with only 75 trained rheumatologists. To address the needs of rheumatology care, it is of paramount importance to train the primary care physician as a first line of defense. METHODS: The project "Empowering Family Physicians; fighting disability" was the recipient of a 2018 ILAR grant. This project began with development of an evidence-based curriculum using ACR Rheum2learn modules along with guidelines from international societies. A blended learning approach was chosen with nine online learning modules sandwiched between two face-to-face sessions. Participants' assessment entailed quizzes, clinical scenarios, and portfolio development all completed online, while face-to-face sessions relied upon power-point presentations and an objective structured clinical examination. Course impact was assessed with pre-course and post-course questionnaires. Overall perception of the training was evaluated through candidate feedback. RESULTS: Participants were enrolled from across the country totaling 48 health care providers (44 family physicians and 4 allied health professionals). The adherence to face-to-face sessions was 82.5% and 63.6% for the online component. The mean score for post-course assessment (mean = 2.369, SD = 0.3425) was significantly higher than for the pre-course assessment (mean = 1.792, SD = 0.4838) with statistically significant difference of, t (12) = - 7.756, p < 0.0001 (confidence interval: - 0.7390 to - 0.4149). The perception of the strategy was positive with 80% strongly satisfied with the workshops and presentations. CONCLUSION: Empowering family physicians by training them in rheumatology care can be an effective tool to fight unmet needs in access to musculoskeletal health care. We plan to offer a shortened version of the course at regular intervals.Key Points• Pakistan has a huge shortage of rheumatology care with only 75 rheumatologists caring for a population of over 200 million.• To improve access to rheumatology care,the "Empowering Family Physicians; Fighting disability" course was launched in 2018 with the help of anILAR grant.• A blended learning approach comprising of 9 online modules sandwiched between two face-to-face sessions was chosen.• A statistically significant difference between pre- and post-courseself-assessment of participantssuggests that the courseis an effective tool for teaching Family Physicians.


Assuntos
Currículo , Empoderamento , Médicos de Família/psicologia , Reumatologia/educação , Humanos , Aprendizagem , Sistemas On-Line , Paquistão , Inquéritos e Questionários
15.
ACR Open Rheumatol ; 1(10): 649-656, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31872187

RESUMO

Objective: Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. Methods: A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA-SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. Results: The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. Conclusion: Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.

16.
Proc Natl Acad Sci U S A ; 116(50): 25222-25228, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31754025

RESUMO

Neutrophil dysregulation is implicated in the pathogenesis of systemic lupus erythematosus (SLE). SLE is characterized by elevated levels of a pathogenic neutrophil subset known as low-density granulocytes (LDGs). The origin and phenotypic, functional, and pathogenic heterogeneity of LDGs remain to be systematically determined. Transcriptomics and epigenetic assessment of lupus LDGs, autologous normal-density neutrophils, and healthy control neutrophils was performed by bulk and single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. Functional readouts were compared among neutrophil subsets. SLE LDGs display significant transcriptional and epigenetic heterogeneity and comprise 2 subpopulations of intermediate-mature and immature neutrophils, with different degrees of chromatin accessibility and differences in transcription factor motif analysis. Differences in neutrophil extracellular trap (NET) formation, oxidized mitochondrial DNA release, chemotaxis, phagocytosis, degranulation, ability to harm the endothelium, and responses to type I interferon (IFN) stimulation are evident among LDG subsets. Compared with other immune cell subsets, LDGs display the highest expression of IFN-inducible genes. Distinct LDG subsets correlate with specific clinical features of lupus and with the presence and severity of coronary artery disease. Phenotypic, functional, and pathogenic neutrophil heterogeneity are prevalent in SLE and may promote immune dysregulation and prominent vascular damage characteristic of this disease.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Neutrófilos/metabolismo , Adulto , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Epigênese Genética , Armadilhas Extracelulares/metabolismo , Feminino , Granulócitos/metabolismo , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma
17.
Ann Rheum Dis ; 78(9): 1151-1159, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31383717

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Doenças Reumáticas , Reumatologia , Sociedades Médicas , Humanos
18.
Lupus Sci Med ; 6(1): e000332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413851

RESUMO

Objective: Subjects with SLE display an enhanced risk of atherosclerotic cardiovascular disease (CVD) that is not explained by Framingham risk. This study sought to investigate the utility of nuclear MR (NMR) spectroscopy measurements of serum lipoprotein particle counts and size and glycoprotein acetylation (GlycA) burden to predict coronary atherosclerosis in SLE. Methods: Coronary plaque burden was assessed in SLE subjects and healthy controls using coronary CT angiography. Lipoproteins and GlycA were quantified by NMR spectroscopy. Results: SLE subjects displayed statistically significant decreases in high-density lipoprotein (HDL) particle counts and increased very low-density lipoprotein (VLDL) particle counts compared with controls. Non-calcified coronary plaque burden (NCB) negatively associated with HDL subsets whereas it positively associated with VLDL particle counts in multivariate adjusted models. GlycA was significantly increased in SLE sera compared with controls. In contrast to high-sensitivity C reactive protein, elevations in GlycA in SLE significantly associated with NCB and insulin resistance (IR), though the association with NCB was no longer significant after adjusting for prednisone use. Conclusions: Patients with SLE display a proatherogenic lipoprotein profile that may significantly contribute to the development of premature CVD. The results demonstrate that NMR measures of GlycA and lipoprotein profiles, beyond what is captured in routine clinical labs, could be a useful tool in assessing CVD risk in patients with SLE.

19.
Arthritis Rheumatol ; 71(9): 1400-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31385462

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/análise , Técnicas de Apoio para a Decisão , Técnica Delfos , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sociedades Médicas , Estados Unidos
20.
Front Immunol ; 10: 1327, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249572

RESUMO

Pulmonary involvement in primary Sjögren's syndrome (pSS) is an understudied entity with important clinical implications. Its prevalence has been reported in up to 20% of pSS patients. Pulmonary manifestations of pSS are diverse with involvement of airway and/or lung parenchyma. Histopathology of lung lesions suggests a predominance of submucosal mononuclear cell infiltration consisting predominantly of CD4+ T cells. Current understanding of the pathophysiology of lung disease in pSS suggests a similar process driving the pulmonary process as those in the salivary glands, with epithelial cells playing a critical role in the initiation, maintenance, and symptomatology of the disease. Clinical manifestations of lung involvement in pSS are as varied as the underlying pathology and can be vague and non-specific, thus delaying diagnosis. Management options depend on the underlying pathology but are generally limited due to lack of systematic randomized controlled trials. This review helps summarize our current understanding of lung involvement in pSS.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pulmão/imunologia , Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologia , Animais , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/terapia
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