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1.
Lupus Sci Med ; 8(1)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33737451

RESUMO

OBJECTIVE: Hydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE. METHODS: Platelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose. RESULTS: Among 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=-0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=-0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056). CONCLUSION: HCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.

2.
J Exp Med ; 218(5)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33783474

RESUMO

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3-sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.

3.
J Rheumatol ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259328

RESUMO

OBJECTIVE: APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine a) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and b) predictors of unstable aPL profiles over time. METHODS: Clinically meaningful aPL profile was defined as positive lupus anticoagulant (LA) test and/or anticardiolipin (aCL)/anti-ß2 glycoprotein-I (aß2GPI) IgG/M ≥40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis. RESULTS: Of 472 patients with clinically meaningful aPL profile at baseline (median follow up: 5.1 years), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable; and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (p=0.906) and multivariable analysis (p=0.790). Baseline triple aPL positivity decreased (Odds Ratio [OR] 0.25, 95% Confidence Interval [CI] 0.10-0.64, p=0.004) and isolated LA test positivity increased (OR 3.3, 95% CI 1.53-7.13, p=0.002) the odds of an unstable aPL profile over time. CONCLUSION: Approximately 80% of our international cohort patients with clinically meaningful aPL profile at baseline maintain such at a median follow-up of five years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32986935

RESUMO

OBJECTIVE: To describe baseline characteristics of antiphospholipid antibody (aPL)-positive patients, overall and by clinical and laboratory subtypes, enrolled in an international registry. METHODS: AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry includes persistently aPL-positive adults. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS [TAPS] only, obstetric APS [OAPS] only, and both TAPS/OAPS). We assessed baseline characteristics of patients tested for three aPL (lupus anticoagulant test [LA], anticardiolipin antibody [aCL], and anti-ß2 -Glycoprotein-I [aß2 GPI]) by aPL profiles (LA only, single, double, and triple aPL positivity). RESULTS: Of 804 aPL-positive patients (mean age: 45 ± 13y; female: 74%; white 68%; other systemic autoimmune diseases: 36%), 80% were classified as APS (55% TAPS, 9% OAPS, and 15% TAPS/OAPS). In the overall cohort, 71% had vascular thrombosis, 50% with pregnancy history had obstetric morbidity, and 56% had at least one non-criteria manifestation. Among those with three aPL tested (n: 660), 42% were triple aPL positive. While single, double and triple aPL positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup consisting of aCL or aß2 GPI only. CONCLUSION: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter, international cohort. Within single aPL-positivity, LA may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification.

6.
Am J Case Rep ; 21: e927418, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32917848

RESUMO

BACKGROUND Patients receiving immunosuppressive therapies might be more susceptible to COVID-19. Conversely, an exaggerated inflammatory response to the SARS-CoV-2 infection might be blunted by certain forms of immunosuppression, which could be protective. Indeed, there are data from animal models demonstrating that complement may be a part of the pathophysiology of coronavirus infections. There is also evidence from an autopsy series demonstrating complement deposition in the lungs of patients with COVID-19. This raises the question of whether patients on anti-complement therapy could be protected from COVID-19. CASE REPORT Case 1 is a 39-year-old woman with an approximately 20-year history of paroxysmal nocturnal hemoglobinuria (PNH), who had recently been switched from treatment with eculizumab to ravulizumab prior to SARS-CoV-2 infection. Case 2 is a 54-year-old woman with a cadaveric renal transplant for lupus nephritis, complicated by thrombotic microangiopathy, who was maintained on eculizumab, which she started several months before she developed the SARS-CoV-2 infection. Case 3 is a 60-year-old woman with a 14-year history of PNH, who had been treated with eculizumab since 2012, and was diagnosed with COVID-19 at the time of her scheduled infusion. All 3 patients had a relatively mild course of COVID-19. CONCLUSIONS We see no evidence of increased susceptibility to SARS-CoV-2 in these patients on anti-complement therapy, which might actually have accounted for the mild course of infection. The effect of anti-complement therapy on COVID-19 disease needs to be determined in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Complemento C5/metabolismo , Infecções por Coronavirus/complicações , Hemoglobinúria Paroxística/tratamento farmacológico , Pneumonia Viral/complicações , Microangiopatias Trombóticas/tratamento farmacológico , Adulto , Betacoronavirus , Complemento C5/efeitos dos fármacos , Complemento C5/imunologia , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/epidemiologia , Feminino , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/imunologia , Humanos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/imunologia
7.
Arthritis Res Ther ; 22(1): 191, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807233

RESUMO

BACKGROUND: Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients. METHODS: Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation. RESULTS: Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient's preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%). CONCLUSIONS: In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.

8.
Arthritis Rheumatol ; 72(12): 1971-1980, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32715660

RESUMO

OBJECTIVE: To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID-19) and to analyze associations of comorbidities and medications on infection outcomes. METHODS: Patients with SLE and reverse transcriptase-polymerase chain reaction-confirmed COVID-19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web-based questionnaire and review of medical records. Data on baseline characteristics were obtained for all patients with COVID-19 to analyze risk factors for hospitalization. Data were also collected on asymptomatic patients and those with COVID-19-like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID-19-positive patients. RESULTS: A total of 226 SLE patients were included: 41 with confirmed COVID-19, 19 who tested negative for COVID-19, 42 with COVID-19-like symptoms who did not get tested, and 124 who remained asymptomatic without testing. Of the SLE patients with confirmed COVID-19, hospitalization was required in 24 (59%) and intensive care unit-level of care in 4, and 4 died. Hospitalized patients tended to be older, nonwhite, Hispanic, have higher body mas index (BMI), history of nephritis, and at least 1 comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least 1 comorbidity, and BMI as independent predictors of hospitalization. CONCLUSION: In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID-19 outcomes in patients with SLE.

9.
JCI Insight ; 5(12)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32396533

RESUMO

Lupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), has a heterogeneous clinical and pathological presentation. For example, proliferative nephritis identifies a more aggressive disease class that requires immunosuppression. However, the current classification system relies on the static appearance of histopathological morphology, which does not capture differences in the inflammatory response. Therefore, a biomarker grounded in the disease biology is needed in order to understand the molecular heterogeneity of lupus nephritis and identify immunologic mechanism and pathways. Here, we analyzed the patterns of 1000 urine protein biomarkers in 30 patients with active lupus nephritis. We found that patients stratify over a chemokine gradient inducible by IFN-γ. Higher values identified patients with proliferative lupus nephritis. After integrating the urine proteomics with the single-cell transcriptomics of kidney biopsies, we observed that the urinary chemokines defining the gradient were predominantly produced by infiltrating CD8+ T cells, along with natural killer and myeloid cells. The urine chemokine gradient significantly correlated with the number of kidney-infiltrating CD8+ cells. These findings suggest that urine proteomics can capture the complex biology of the kidney in lupus nephritis. Patient-specific pathways could be noninvasively tracked in the urine in real time, enabling diagnosis and personalized treatment.

10.
Arthritis Care Res (Hoboken) ; 72(2): 233-242, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31502417

RESUMO

The Accelerating Medicines Partnership (AMP) Lupus Network was established as a partnership between the National Institutes of Health, pharmaceutical companies, nonprofit stakeholders, and lupus investigators across multiple academic centers to apply high-throughput technologies to the analysis of renal tissue, urine, and blood from patients with lupus nephritis (LN). The AMP network provides publicly accessible data to the community with the goal of generating new scientific hypotheses and improving diagnostic and therapeutic tools so as to improve disease outcomes. We present here a description of the structure of the AMP Lupus Network and a summary of the preliminary results from the phase 1 studies. The successful completion of phase 1 sets the stage for analysis of a large cohort of LN samples in phase 2 and provides a model for establishing similar discovery cohorts.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Ensaios Clínicos Fase I como Assunto/métodos , Indústria Farmacêutica/organização & administração , Nefrite Lúpica/metabolismo , National Institutes of Health (U.S.)/organização & administração , Dados Preliminares , Parcerias Público-Privadas/organização & administração , Biomarcadores/metabolismo , Humanos , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/genética , Análise de Sequência de RNA/métodos , Estados Unidos/epidemiologia
11.
Lupus Sci Med ; 6(1): e000344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798917

RESUMO

Objective: Epidemiological data for primary discoid lupus erythematosus (pDLE) remain limited, particularly for racial/ethnic populations in the USA. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases with SLE and related diseases including pDLE in Manhattan and was used to provide estimates of the prevalence and incidence of pDLE across major racial/ethnic populations. Methods: MLSP cases were identified from rheumatologists, hospitals and population databases. Two case definitions were used for pDLE: the primary case definition which was any physician diagnosis found in the chart and a secondary case definition which was limited to cases diagnosed by a rheumatologist and/or dermatologist. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess case under-ascertainment. Results: Based on the primary definition, age-adjusted overall prevalence and incidence rates of pDLE among Manhattan residents were 6.5 and 0.8 per 100 000 person-years, which increased to 9.0 and 1.3 after capture-recapture adjustment. Prevalence and incidence rates were approximately two and six times higher, respectively, among women compared with men (p<0.0001). Higher prevalence was also found among non-Latino blacks (23.5) and Latinos (8.2) compared with non-Latino whites (1.8) and non-Latino Asians (0.6) (p<0.0001). Incidence was highest among non-Latino blacks (2.4) compared with all other racial/ethnic groups. Similar relationships were observed for the secondary case definition. Conclusion: Data from the MLSP provide epidemiological estimates for pDLE among the major racial/ethnic populations in the USA and reveal disparities in pDLE prevalence and incidence by sex and race/ethnicity among Manhattan residents.

13.
J Thromb Haemost ; 17(12): 2069-2080, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31364274

RESUMO

BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Ensaio de Proficiência Laboratorial , Inibidor de Coagulação do Lúpus/sangue , Testes Sorológicos/normas , Anticoagulantes/sangue , Síndrome Antifosfolipídica/sangue , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Tempo de Protrombina/normas , Sistema de Registros , Reprodutibilidade dos Testes
14.
Semin Arthritis Rheum ; 49(3): 464-468, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31153708

RESUMO

OBJECTIVES: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. METHODS: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ("Registry"). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-ß2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. RESULTS: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ±â€¯3.3 vs. 6 ±â€¯3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ±â€¯3.9; p<0.05). CONCLUSIONS: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/diagnóstico , Sistema de Registros , Medição de Risco/métodos , Trombose/etiologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Biomarcadores/sangue , Estudos Transversais , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/epidemiologia
15.
Nat Immunol ; 20(7): 915-927, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31110316

RESUMO

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.


Assuntos
Perfilação da Expressão Gênica , Interferon Tipo I/metabolismo , Queratinócitos/metabolismo , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Transcriptoma , Biópsia , Linhagem da Célula/genética , Biologia Computacional/métodos , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose , Perfilação da Expressão Gênica/métodos , Humanos , Nefrite Lúpica/patologia , Ligação Proteica , Transdução de Sinais , Análise de Célula Única , Pele/imunologia , Pele/metabolismo , Pele/patologia
16.
Arthritis Care Res (Hoboken) ; 71(1): 134-141, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29669399

RESUMO

OBJECTIVE: Although systemic lupus erythematosus (SLE) is the most common autoimmune disease associated with antiphospholipid antibodies (aPL), limited data exist regarding the impact of SLE on the clinical phenotype of aPL-positive patients. The primary objective of this study was to compare the clinical, laboratory, and treatment characteristics of aPL-positive patients with SLE with those of aPL-positive patients without SLE. METHODS: A secure web-based data capture system was used to store patient demographic characteristics and aPL-related clinical and laboratory characteristics. Inclusion criteria included positive aPL according to the updated Sapporo classification criteria. Antiphospholipid antibody-positive patients fulfilling the American College of Rheumatology criteria for the classification of SLE ("aPL with SLE") and those with no other autoimmune diseases ("aPL only") were included in the analysis. RESULTS: Six hundred seventy-two aPL-positive patients were recruited from 24 international centers; 426 of these patients did not have other autoimmune disease, and 197 had SLE. The frequency of thrombocytopenia, hemolytic anemia, low complement levels, and IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) antibodies was higher in the aPL-positive patients with SLE, whereas the frequency of cognitive dysfunction and IgG anti-ß2 GPI antibodies was higher in the aPL-only group. The frequency of arterial and venous thromboses (including recurrent) as well as pregnancy morbidity was similar in the 2 groups. The prevalence of cardiovascular disease risk factors at the time of entry into the registry entry did not differ between the 2 groups, with the exception of current smoking, which was more frequent in aPL-positive patients with SLE. CONCLUSION: Although the frequencies of thrombosis and pregnancy morbidity are similar in aPL-positive patients with and those without SLE, the diagnosis of SLE in patients with persistently positive aPL is associated with an increased frequency of thrombocytopenia, hemolytic anemia, low complement levels, and positive IgA anti-ß2 GPI antibodies.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/epidemiologia , Bases de Dados Factuais , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Fenótipo , Adulto , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , Internacionalidade , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Gravidez , Sistema de Registros
17.
J Magn Reson Imaging ; 50(2): 490-496, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30548522

RESUMO

BACKGROUND: Osteoporosis (OP) results in weak bone and can ultimately lead to fracture. Drugs such as glucocorticoids can also induce OP (glucocorticoid-induced osteoporosis [GIO]). Bone marrow adipose tissue composition and quantity may play a role in OP pathophysiology, but has not been thoroughly studied in GIO compared to primary OP. PURPOSE/HYPOTHESIS: Chemical shift-encoded (CSE) MRI allows detection of subregional differences in bone marrow adipose tissue composition and quantity in the proximal femur of GIO compared to OP subjects and has high agreement with the reference standard of magnetic resonance spectroscopy (MRS). STUDY TYPE: Prospective. SUBJECTS: In all, 18 OP and 13 GIO subjects. FIELDS STRENGTH: 3T. SEQUENCE: Multiple gradient-echo, stimulated echo acquisition mode (STEAM). ASSESSMENT: Subjects underwent CSE-MRI in the proximal femurs, and for each parametric map regions of interest (ROIs) were assessed in the femoral head (fHEAD), femoral neck (fNECK), Ward's triangle (fTRIANGLE), and the greater trochanter (GTROCH). In addition, we compared CSE-MRI against the reference standard of MRS performed in the femoral neck and Ward's triangle. STATISTICAL TESTS: Differences between OP/GIO were investigated using the Mann-Whitney nonparametric test. Bland-Altman methodology was used to assess measurement agreement between CSE-MRI and MRS. RESULTS: GIO compared with OP subjects demonstrated: decreased monounsaturated fat fraction (MUFA) (-2.1%, P < 0.05) in fHEAD; decreased MUFA (-3.8%, P < 0.05), increased saturated fat fraction (SFA) (5.5%, P < 0.05), and decreased T 2 * (-3.8 msec, P < 0.05) in fNECK; decreased proton density fat fraction (PDFF) (-15.1%, P < 0.05), MUFA (-9.8%, P < 0.05), polyunsaturated fat fraction (PUFA) (-1.8%, P < 0.01), increased SFA (11.6%, P < 0.05), and decreased T 2 * (-5.4 msec, P < 0.05) in fTRIANGLE; and decreased T 2 * (-1.5 msec, P < 0.05) in GTROCH. There was high measurement agreement between MRI and MRS using the Bland-Altman test. DATA CONCLUSION: 3T CSE-MRI may allow reliable assessment of subregional bone marrow adipose tissue (bMAT) quantity and composition in the proximal femur in a clinically reasonable scan time. Glucocorticoids may alter the lipid profile of bMAT and potentially result in reduced bone quality. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:490-496.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Glucocorticoides/efeitos adversos , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico por imagem , Adolescente , Adulto , Idoso , Algoritmos , Densidade Óssea , Medula Óssea/diagnóstico por imagem , Ácidos Graxos/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Arthritis Care Res (Hoboken) ; 71(7): 949-960, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30044541

RESUMO

OBJECTIVE: Extant epidemiologic data of primary Sjögren's syndrome (SS) remains limited, particularly for racial/ethnic populations in the US. The Manhattan Lupus Surveillance Program (MLSP) is a population-based retrospective registry of cases of systemic lupus erythematosus and related diseases, including primary SS in Manhattan, New York. The MLSP was used to provide estimates of the incidence and prevalence of primary SS across major racial/ethnic populations. METHODS: MLSP cases were identified from hospitals, rheumatologists, and population databases. Three case definitions were used for primary SS, including physician diagnosis, rheumatologist diagnosis, and modified primary SS criteria. Rates among Manhattan residents were age-adjusted, and capture-recapture analyses were conducted to assess underascertainment of cases. RESULTS: By physician diagnosis, age-adjusted overall incidence and prevalence rates of primary SS among adult Manhattan residents were 3.5 and 13.1 per 100,000 person-years, respectively. Capture-recapture adjustment increased incidence and prevalence rates (4.1 and 14.2 per 100,000 person-years, respectively). Based on physician diagnosis, incidence and prevalence rates were approximately 6 times higher among women than men (P < 0.001). Incidence of primary SS was statistically higher among non-Latina Asian women (10.5) and non-Latina white women (6.2) compared with Latina women (3.2). Incidence was also higher among non-Latina Asian women compared with non-Latina black women (3.3). Prevalence of primary SS did not differ by race/ethnicity. Similar trends were observed when more restrictive case definitions were applied. CONCLUSION: Data from the MLSP revealed disparities among Manhattan residents in primary SS incidence and prevalence by sex and differences in primary SS incidence by race/ethnicity among women. These data also provided epidemiologic estimates for the major racial/ethnic populations in the US.


Assuntos
Síndrome de Sjogren/epidemiologia , Adulto , Distribuição por Idade , Idoso , Grupos de Populações Continentais , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Prevalência , Sistema de Registros , Fatores de Risco , Distribuição por Sexo , Síndrome de Sjogren/diagnóstico , Fatores de Tempo
19.
Lupus Sci Med ; 5(1): e000271, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233806

RESUMO

Objectives: The study aimed to determine if serum albumin at 12 months predicts long-term renal outcome at 48 months. Data from the NYU SAMPLE (Specimen and Matched Phenotype Linked Evaluation) Lupus Registry were used to compare the performance of albumin, anti-double-stranded DNA, C3/C4, proteinuria and haematuria. Methods: 82 patients with SLE with data at time of renal biopsy, at 12 months and at a second visit, and up to 48 months were included. The significance of each biomarker as a predictor of an adverse renal outcome (ARO), defined as doubling of serum creatinine, as creatinine >4 mg/dL if initial >2.5 mg/dL or ESRD, was evaluated in univariate and exploratory multivariable Cox proportional hazards models. Hazard ratios (HRs) for ARO with 95% CIs were generated. The receiver operating characteristic (ROC) curves at 48 months were used to identify the optimal cut-off point for albumin and proteinuria to predict ARO. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for albumin and proteinuria. Results: Serum albumin and proteinuria had statistically significant HRs for ARO (0.140 and 1.459, respectively). The model with both albumin and proteinuria indicated no additional independent contribution of proteinuria to albumin alone. The ROC curves identified cut-offs of 3.7 g/dL for albumin and 0.964 urine protein to creatinine ratio for proteinuria. Albumin had a sensitivity of 94%, specificity of 87%, PPV of 64% and NPV of 98%. Conclusions: This study demonstrates serum albumin >3.7 g/dL is a predictor of a favourable long-term renal outcome. These results support the inclusion of albumin as an outcome in lupus nephritis trials and treat-to-target guidelines.

20.
Semin Arthritis Rheum ; 48(2): 256-262, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29395256

RESUMO

OBJECTIVE: To study membrane attack complex in lupus nephritis as a potential biomarker for disease intensity and prognostic indicator for response to treatment. METHODS: Immunohistochemistry was performed using unconjugated, murine anti-human complement C9 on kidney biopsies from 30 SLE patients who fulfilled 4 ACR or SLICC criteria. Clinical parameters were assessed at time of biopsy, 6 and 12 months. RESULTS: 30 renal biopsies were obtained from patients with Class II (2), III (5), IV (8), V (5), III+V (8) and IV+V (2). 13/30 (43.3%) biopsies stained positive for glomerular C9. Patients with positive C9 had significantly higher blood pressure, trend towards lower C3, and male gender. There was no significant difference for ISN/RPN class, activity or chronicity indices between C9 positive and negative groups. 5/11 (45.5%) patients positive for C9 did not respond to therapy at 6 months compared with 2/15 (13.3%) patients negative for C9. C9 positive patients were more likely to be a non-responder at 6 months (OR = 5.4, 95% CI: 0.8, 36.4) compared to C9 negative patients. After adjusting for systolic blood pressure, compliance to treatment and proteinuria in a multivariate logistic model, C9 positive patients remained more likely to be non-responders (OR = 4.6, 95% CI: 0.3, 70.9). CONCLUSION: This study suggests that MAC deposition measured as C9 staining may be a biomarker for more intense disease and poor response to treatment in lupus nephritis. MAC staining may be useful in routine studies of lupus biopsies and identify patients at risk for aggressive disease who may be candidates for novel therapies targeting terminal complement pathway.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Hipertensão/metabolismo , Imunossupressores/uso terapêutico , Rim/metabolismo , Nefrite Lúpica/metabolismo , Adulto , Feminino , Humanos , Hipertensão/complicações , Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
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