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1.
Artigo em Inglês | MEDLINE | ID: mdl-33555325

RESUMO

OBJECTIVES: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels. RESULTS: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased HDL were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. CONCLUSIONS: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32813314

RESUMO

OBJECTIVE: To assess cancer risk factors in incident SLE. METHODS: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (over-all risk, and most common cancers) included demographics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and adjusted mean SLE Disease Activity Index-2K. RESULTS: Among 1668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 non-melanoma skin, seven lung, six hematological, six prostate, five melanoma, three cervical, three renal, two each gastric, head and neck, and thyroid, and one each rectal, sarcoma, thymoma, and uterine cancers. Half of cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively and anti-malarial drugs were negatively associated. Anti-malarial drugs and higher disease activity were also negatively associated with non-melanoma skin cancer (NMSC) risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with NMSC risk. CONCLUSIONS: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and NMSC. Antimalarials were negatively associated with breast cancer and NMSC risk. SLE activity was associated positively with hematologic cancer and negatively with NMSC. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.

3.
Arthritis Rheumatol ; 72(10): 1734-1740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32515554

RESUMO

OBJECTIVE: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. METHODS: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models. RESULTS: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001). CONCLUSION: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32433832

RESUMO

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 SLE classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list-based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria, and compared its performance to the revised ACR 1997, unweighted SLICC 2012 and the newly reported European League Against Rheumatism (EULAR)/ACR 2019 criteria. METHODS: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were re-employed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules. RESULTS: Weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis. CONCLUSION: The two new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a dataset originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived, and whether the goal is to prioritize sensitivity or specificity.

5.
Ann Rheum Dis ; 79(3): 356-362, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31915121

RESUMO

OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/mortalidade , Vasculite Associada ao Lúpus do Sistema Nervoso Central/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multinível , Estudos Prospectivos , Qualidade de Vida
6.
J Autoimmun ; 106: 102340, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31629628

RESUMO

OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. METHODS: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). RESULTS: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03-1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). CONCLUSION: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

7.
Rheumatology (Oxford) ; 58(7): 1259-1267, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753683

RESUMO

OBJECTIVES: To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. METHODS: This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. RESULTS: A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. CONCLUSION: CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.


Assuntos
Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Adulto , Síndrome Antifosfolipídica/complicações , Estudos de Coortes , Contraindicações de Medicamentos , Uso de Medicamentos/estatística & dados numéricos , Escolaridade , Feminino , Humanos , Hipertensão/complicações , Enxaqueca com Aura/complicações , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
8.
J Rheumatol ; 46(5): 492-500, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30647177

RESUMO

OBJECTIVE: In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. METHODS: We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. RESULTS: Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). CONCLUSION: The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/epidemiologia , Osteopontina/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Ásia , Biomarcadores/sangue , Criança , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Europa (Continente) , Feminino , Seguimentos , Humanos , Internacionalidade , Modelos Logísticos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , América do Norte , Valores de Referência , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
9.
Kidney Int ; 95(1): 219-231, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30420324

RESUMO

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Adulto , Inibidores de Calcineurina/efeitos adversos , Ciclosporina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Indução de Remissão/métodos , Resultado do Tratamento , Adulto Jovem
10.
Ann Rheum Dis ; 78(7): 1010-1012, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30573656
11.
Rheumatology (Oxford) ; 57(4): 677-687, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361147

RESUMO

Objectives: To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods: Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time. Results: We studied 1700 patients with a mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis. Conclusion: GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Grupos Étnicos , Glucocorticoides/administração & dosagem , Nível de Saúde , Cooperação Internacional , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Algoritmos , Ásia/epidemiologia , Estudos Transversais , Progressão da Doença , Relação Dose-Resposta a Droga , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Morbidade/tendências , América do Norte/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
12.
Arthritis Care Res (Hoboken) ; 70(1): 98-103, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28388813

RESUMO

OBJECTIVE: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. METHODS: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. RESULTS: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. CONCLUSION: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.


Assuntos
Técnicas de Apoio para a Decisão , Lúpus Eritematoso Sistêmico/diagnóstico , Registros Médicos , Inquéritos e Questionários , Competência Clínica , Consenso , Progressão da Doença , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
13.
Arthritis Res Ther ; 19(1): 287, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273092

RESUMO

BACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. METHODS: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event. RESULTS: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety. CONCLUSIONS: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Nucleossomos/metabolismo , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Clin Immunol ; 168: 16-24, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27102764

RESUMO

The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/ß) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/ß frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD.


Assuntos
Sistema Imunitário/citologia , Interferon Tipo I/imunologia , Rim/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Urina/citologia , Adulto , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Células Dendríticas/imunologia , Feminino , Citometria de Fluxo , Humanos , Sistema Imunitário/imunologia , Memória Imunológica/imunologia , Interferon Tipo I/sangue , Interferon Tipo I/urina , Interferon-alfa/sangue , Interferon-alfa/imunologia , Interferon-alfa/urina , Interferon beta/sangue , Interferon beta/imunologia , Interferon beta/urina , Rim/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/imunologia , Falência Renal Crônica/urina , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/urina , Nefrite Lúpica/sangue , Nefrite Lúpica/urina , Masculino , Plasmócitos/imunologia
15.
Rheumatology (Oxford) ; 55(2): 252-62, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26342222

RESUMO

OBJECTIVE: To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores. RESULTS: There were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR <30 ml/min at diagnosis had lower SF-36 physical component summary scores (P < 0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and proteinuria had lower SF-36 mental component summary (P ≤ 0.02) scores compared to patients with normal values. CONCLUSION: LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower health-related quality of life. Further advances are required for the optimal treatment of LN.


Assuntos
Grupos Étnicos , Nefrite Lúpica/etnologia , Avaliação de Resultados em Cuidados de Saúde , Adulto , Progressão da Doença , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Nefrite Lúpica/diagnóstico , Masculino , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida/tendências
16.
Arthritis Res Ther ; 17: 110, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25927414

RESUMO

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations. Although the approval of new therapies includes only one agent in 50 years, a number of promising new drugs are in development. Lupus nephritis is a dreaded complication of SLE as it is associated with significant morbidity and mortality. Advancing the treatment of lupus nephritis requires well-designed clinical trials and this can be challenging in SLE. The major obstacles involve identifying the correct population of patients to enroll and ensuring that a clinically appropriate and patient-centered endpoint is being measured. In this review, we will first discuss the clinical utility of endpoints chosen to represent lupus nephritis in global disease activity scales. Second, we will review completed and active trials focused on lupus nephritis and discuss the endpoints chosen. There are many important lessons to be learned from existing assessment tools and clinical trials. Reviewing these points will help ensure that future efforts will yield meaningful disease activity measures and well-designed clinical trials to advance our understanding of lupus management.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/prevenção & controle , Corticosteroides/uso terapêutico , Progressão da Doença , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Testes de Função Renal , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/fisiopatologia , Masculino , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controle , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Ann Rheum Dis ; 74(9): 1706-13, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24834926

RESUMO

BACKGROUND AND AIMS: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. RESULTS: We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). CONCLUSIONS: Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.


Assuntos
Grupos Étnicos , Nível de Saúde , Lúpus Eritematoso Sistêmico/fisiopatologia , Qualidade de Vida , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Adulto Jovem
18.
Arthritis Care Res (Hoboken) ; 67(1): 128-35, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24838943

RESUMO

OBJECTIVE: To estimate the early prevalence of various electrocardiographic (EKG) abnormalities in patients with systemic lupus erythematosus (SLE) and to evaluate possible associations between repolarization changes (increased corrected QT [QTc] and QT dispersion [QTd]) and clinical and laboratory variables, including the anti-Ro/SSA level and specificity (52 or 60 kd). METHODS: We studied adult SLE patients from 19 centers participating in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Registry. Demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), disease damage (SLICC/American College of Rheumatology Damage Index [SDI]), and laboratory data from the baseline or first followup visit were assessed. Multivariate logistic and linear regression models were used to asses for any cross-sectional associations between anti-Ro/SSA and EKG repolarization abnormalities. RESULTS: For the 779 patients included, mean ± SD age was 35.2 ± 13.8 years, 88.4% were women, and mean ± SD disease duration was 10.5 ± 14.5 months. Mean ± SD SLEDAI-2K score was 5.4 ± 5.6 and mean ± SD SDI score was 0.5 ± 1.0. EKG abnormalities were frequent and included nonspecific ST-T changes (30.9%), possible left ventricular hypertrophy (5.4%), and supraventricular arrhythmias (1.3%). A QTc ≥440 msec was found in 15.3%, while a QTc ≥460 msec was found in 5.3%. Mean ± SD QTd was 34.2 ± 14.7 msec and QTd ≥40 msec was frequent (38.1%). Neither the specificity nor the level of anti-Ro/SSA was associated with QTc duration or QTd, although confidence intervals were wide. Total SDI was significantly associated with a QTc interval exceeding 440 msec (odds ratio 1.38 [95% confidence interval 1.06, 1.79]). CONCLUSION: A substantial proportion of patients with recent-onset SLE exhibited repolarization abnormalities, although severe abnormalities were rare.


Assuntos
Eletrocardiografia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Estudos de Coortes , Estudos Transversais , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Internacionalidade , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Adulto Jovem
19.
Ann Rheum Dis ; 74(8): 1530-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24692585

RESUMO

BACKGROUND: The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. METHODS: Recently diagnosed (<15 months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. RESULTS: We studied 1150 patients with a mean (SD) age of 34.9 (13.6) years and disease duration at enrolment of 24.2 (18.0) weeks. In those with complete data, MetS prevalence was 38.2% at enrolment, 34.8% at year 1 and 35.4% at year 2. In a multivariable random effects model that included data from all visits, prior MetS status, baseline renal disease, SLICC Damage Index >1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort. CONCLUSIONS: MetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course.


Assuntos
Lúpus Eritematoso Sistêmico/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Estudos de Coortes , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Adulto Jovem
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