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1.
Artigo em Inglês | MEDLINE | ID: mdl-31628482

RESUMO

OBJECTIVES: 3-hydroxy-3-methylglutaryl coenzyme-A (HMG Co-A) reductase inhibitors (statins) are standard treatment for hyperlipidaemia. In addition to lipid-lowering abilities, statins exhibit multiple anti-inflammatory effects. The objectives of this study were to determine whether treatment of patients with RA with lovastatin decreased CRP or reduced disease activity. METHODS: We conducted a randomized double-blind placebo-controlled 12 week trial of lovastatin vs placebo in 64 RA patients with mild clinical disease activity but an elevated CRP. The primary efficacy end point was the reduction in mean log CRP. Secondary end points included disease activity, RF and anti-CCP antibody titres. Mechanistic end points included levels of serum cytokines. Safety was assessed; hepatic and muscle toxicities were of particular interest. RESULTS: Baseline features were similar between groups. No significant difference in mean log CRP reduction between the two groups was observed, and disease activity did not change from baseline in either treatment group. Mechanistic analyses did not reveal significant changes in any biomarkers. A post hoc analysis of subjects not using biologic therapy demonstrated a significantly greater proportion achieving ⩾20% reduction in CRP from baseline in the lovastatin group compared with placebo (P-value = 0.007). No difference was observed in subjects receiving biologics. Lovastatin was well tolerated with no serious safety concerns. CONCLUSION: This study showed no anti-inflammatory or clinical effects on RA disease activity after 12 weeks of treatment with lovastatin. Lovastatin had a modest effect on CRP in subjects not using biologics, suggesting statins may be anti-inflammatory in selected patients. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00302952.

2.
Nat Commun ; 10(1): 3902, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467281

RESUMO

Systemic lupus erythematous (SLE) is a heterogeneous autoimmune disease in which outcomes vary among different racial groups. Here, we aim to identify SLE subgroups within a multiethnic cohort using an unsupervised clustering approach based on the American College of Rheumatology (ACR) classification criteria. We identify three patient clusters that vary according to disease severity. Methylation association analysis identifies a set of 256 differentially methylated CpGs across clusters, including 101 CpGs in genes in the Type I Interferon pathway, and we validate these associations in an external cohort. A cis-methylation quantitative trait loci analysis identifies 744 significant CpG-SNP pairs. The methylation signature is enriched for ethnic-associated CpGs suggesting that genetic and non-genetic factors may drive outcomes and ethnic-associated methylation differences. Our computational approach highlights molecular differences associated with clusters rather than single outcome measures. This work demonstrates the utility of applying integrative methods to address clinical heterogeneity in multifactorial multi-ethnic disease settings.

4.
Nat Immunol ; 20(7): 902-914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209404

RESUMO

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.


Assuntos
Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , Transcriptoma
5.
Lupus Sci Med ; 6(1): e000308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080631

RESUMO

Objective: The outcome of participants with nephrotic syndrome in clinical trials of lupus nephritis has not been studied in detail. Methods: Collated data from two randomised controlled trials in lupus nephritis, Lupus Nephritis Assessment of Rituximab (LUNAR) and A Study to Evaluate Ocrelizumab in Patients With Nephritis due to Systemic Lupus Erythematosus (BELONG) were analysed. Nephrotic syndrome was defined as albumin <3 g/dL and urine protein/creatinine ratio ≥3.5 g/g at start of trial. Renal response was defined as a first morning urine protein/creatinine ratio ≤0.5 g/g in addition to ≤25% increase in creatinine from trial entry assessed at week 48. Logistic regression was used to evaluate the association of nephrotic syndrome with renal response while adjusting for treatment received and ACE inhibitor or angiotensin receptor blocker use. Results: 28 (26%) participants with nephrotic syndrome achieved renal response as compared with 130 (52.5%) of those without (p<0.001). Having nephrotic syndrome at baseline significantly lowered the likelihood of achieving renal response (OR 0.32, 95 % CI 0.19 to 0.54, p<0.001). 125 (80%) participants achieved resolution of their nephrotic syndrome in a median time of 16 weeks. Conclusions: Nephrotic syndrome at baseline decreases the likelihood of renal response at 1 year. Longer clinical trials or better short-term predictors of long-term outcomes may better assess the effect of novel therapeutic approaches on subjects with nephrotic syndrome.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31115180

RESUMO

OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with SLE residing in San Francisco County, California from 2007-2009, with a special focus on Asians/Pacific Islanders (API) and Hispanics. We used retrospective CLSP data to analyze racial/ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: 724 patients with SLE were retrospectively identified. Prevalence ratios (PR) of SLE manifestations were calculated using Poisson regression models stratified by race/ethnicity and adjusted for sex, age at SLE diagnosis, and disease duration. We studied onset of severe SLE manifestations after SLE diagnosis using Kaplan-Meier methods to examine time-to-event and Cox proportional hazards regressions to estimate hazard ratios (HR). Whites were the referent group in all analyses. RESULTS: Blacks, APIs, and Hispanics had increased prevalence of renal manifestations [PR 1.74 (95%CI: 1.40-2.16), PR 1.68 (95%CI: 1.38-2.05), PR 1.35 (95%CI: 1.05-1.74)], respectively. Furthermore, Blacks had increased prevalence of neurologic manifestations [PR 1.49 (95%CI: 1.12-1.98)] and both Blacks [PR 1.09 (95%CI: 1.04-1.15)] and APIs [PR 1.07 (95%CI: 1.01-1.13)] had increased prevalence of hematologic manifestations. Blacks, APIs, and Hispanics, respectively, had higher risk of developing lupus nephritis [HR 2.4 (95%CI: 1.6-3.8), HR 4.3 (95%CI: 2.9-6.4), HR 2.3 (95%CI: 1.4-3.8)] and thrombocytopenia [HR 2.3 (95%CI: 1.1-4.4), HR 2.3 (95%CI: 1.3-4.2), HR 2.2 (95%CI: 1.1-4.7)]. APIs and Hispanics had higher risk of developing antiphospholipid syndrome [HR 2.5 (95%CI: 1.4-4.4), HR 2.6 (95%CI: 1.3-5.1), respectively]. CONCLUSIONS: This is the first epidemiologic study comparing lupus manifestations among four major racial/ethnic groups. We found 1) substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups, and 2) that Blacks, APIs, and Hispanics are at increased risk of developing several severe manifestations following SLE diagnosis. This article is protected by copyright. All rights reserved.

7.
PLoS Med ; 16(5): e1002800, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31067237

RESUMO

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.


Assuntos
Técnicas de Apoio para a Decisão , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Educação de Pacientes como Assunto , Participação do Paciente , Adulto , Comportamento de Escolha , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Alfabetização em Saúde , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/etnologia , Nefrite Lúpica/imunologia , Pessoa de Meia-Idade , Folhetos , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-31069933

RESUMO

PURPOSE: Adverse childhood experiences (ACEs) are associated with poor adult health and immune dysregulation. The impact of ACEs on patients with autoimmune disease is unknown. We compared the prevalence of ACEs in Systemic Lupus Erythematosus (SLE) patients to population-based survey estimate and investigated relationships between ACEs and SLE outcomes. METHODS: Data derive from the California Lupus Epidemiology Study (CLUES), a sample of adult SLE patients. Participants completed a 10-item ACE questionnaire covering 3 domains (abuse, neglect, household challenges). We estimated ACEs prevalence in 269 CLUES participants compared to 2015 California Behavioral Risk Factor Surveillance System (BRFSS) geographically matched respondents, standardized (age, sex, race/ethnicity) to CLUES participant characteristics. We examined associations for patient-reported and physician-assessed health status measures with overall ACE levels and domains using multivariable linear regression, controlling for socio-demographics, nephritis, and childhood onset SLE. RESULTS: Though specific domains varied, overall ACE levels were similar for CLUES and BRFSS respondents. Among SLE patients, 63.2% had ≥1 ACE and 19.3% had ≥4. ACEs were more prevalent in those who were older, women, Latino or African American, without college degrees, and with lupus nephritis. In adjusted models, higher ACE levels and ACE domains were associated with worse patient-reported SLE activity, depression, and health status, but were not significantly associated with physician-assessed SLE activity, damage, or severity. CONCLUSIONS: Given the association between ACE levels and important patient-reported outcomes in SLE, our study reinforces the need for prevention of ACEs in childhood and for clinical interventions to promote resilience among adults who have experienced ACEs. This article is protected by copyright. All rights reserved.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31058460

RESUMO

OBJECTIVE: We examined quality measures for screening, diagnosis and treatment of lupus nephritis (LN) among participants of the California Lupus Epidemiology Study (CLUES) across 25 different clinical sites to identify gaps in quality of care. METHODS: Data from 250 lupus participants was analyzed across three sources (medical records, physician examination, and patient interviews). Overall performance on eight quality measures was calculated separately for participants with and without LN. We used generalized estimating equations in which the outcome was performance on measures, adjusting for participant demographics, lupus disease severity and practice characteristics. RESULTS: Of 148 patients without LN, 42% had screening labs for nephritis, 38% had lupus activity serologies and 81% had blood pressure checked every 6 months. Of 102 LN patients, 67% had a timely kidney biopsy, at least 81% had appropriate treatment and 78% achieved target blood pressure within 1 year of diagnosis. Overall performance in participants across quality measures was 54% (no LN) and 80% (LN). Significantly higher overall performance for screening measures for LN was seen at academic (63.4-73%) versus community clinics (37.9-38.4%). Similarly, among those with LN, higher performance in academic (84.1-85.2%) versus community clinics (54.8-60.2%) was observed for treatment measures. CONCLUSION: In this quality of care analysis across 25 diverse clinical settings, we found relatively high performance on measures for management of LN. However, future work should focus on bridging the gaps in lupus quality of care for patients without nephritis, particularly in community settings. This article is protected by copyright. All rights reserved.

10.
Ann Rheum Dis ; 78(6): 729-735, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30636212

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a considerable impact on patients' quality of life. Despite the plethora of clinical trials for SLE since the turn of the millennium, only one new treatment has been approved for the condition, and the overall pace of successful drug development remains slow. Nevertheless, the myriad of clinical studies has yielded insights that have informed and refined our understanding of eligibility criteria, outcome measures and trial design in SLE. In this review, we highlight the achievements of clinical trials as well as the major pitfalls that have been identified in drug development for SLE and, in doing so, identify areas where collaboration and consensus will be important to facilitate progress.

11.
Arthritis Care Res (Hoboken) ; 71(12): 1630-1639, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30354017

RESUMO

OBJECTIVE: We examined psychometric performance of Patient-Reported Outcomes Measurement Information System (PROMIS) measures in a racially/ethnically and linguistically diverse cohort with systemic lupus erythematosus (SLE). METHODS: Data were from the California Lupus Epidemiology Study, a multiracial/multiethnic cohort of individuals with physician-confirmed SLE. The majority (n = 332) attended in-person research visits that included interviews conducted in English, Spanish, Cantonese, or Mandarin. Up to 12 PROMIS short forms were administered (depending on language availability). An additional 99 individuals completed the interview by phone only. Internal consistency was examined with Cronbach's alpha and item-total correlations. Correlations with the Short Form 36 subscales and both self-reported and physician-assessed disease activity assessed convergent validity. All analyses were repeated within each racial/ethnic group. Differences in scores by race/ethnicity were examined in bivariate analyses and by multiple regression analyses controlling for age, sex, disease duration, and disease damage and activity. RESULTS: The total sample was 30.0% white, 22.3% Hispanic, 10.9% African American, 33.7% Asian, and 3.0% other race/ethnicity. Seventy-seven percent of interviews were conducted in-person. Non-English interviews were conducted in 26.0% of the Hispanic subjects and 18.6% of the Asian subjects. Each scale demonstrated adequate reliability and validity overall and within racial/ethnic groups. Minimal floor effects were observed, but ceiling effects were noted. Missing item responses were minimal for most scales, except for items related to work. No differences were noted by mode of administration or by language of administration among Hispanics and Asians. After accounting for differences in disease status, age, and sex, few differences in mean scores between whites and other racial/ethnic groups were noted. CONCLUSION: PROMIS measures appear reliable and valid in persons with lupus across racial/ethnic groups.

12.
Arthritis Rheumatol ; 71(3): 431-440, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30277008

RESUMO

OBJECTIVE: Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease. METHODS: We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment. RESULTS: Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-γ pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production. CONCLUSION: We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia Adotiva/métodos , Lúpus Eritematoso Sistêmico/terapia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia
13.
Arthritis Rheumatol ; 71(3): 411-419, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225865

RESUMO

OBJECTIVE: End points currently used in lupus nephritis (LN) clinical trials lack uniformity and questionably reflect long-term kidney survival. This study was undertaken to identify short-term end points that predict long-term kidney outcomes for use in clinical trials. METHODS: A database of 944 patients with LN was assembled from 3 clinical trials and 12 longitudinal cohorts. Variables from the first 12 months of treatment after diagnosis of active LN (prediction period) were assessed as potential predictors of long-term outcomes in a 36-month follow-up period. The long-term outcomes examined were new or progressive chronic kidney disease (CKD), severe kidney injury (SKI), and the need for permanent renal replacement therapy (RRT). To predict the risk for each outcome, hazard index tools (HITs) were derived using multivariable analysis with Cox proportional hazards regression. RESULTS: Among 550 eligible subjects, 54 CKD, 55 SKI, and 22 RRT events occurred. Variables in the final CKD HIT were prediction-period CKD status, 12-month proteinuria, and 12-month serum creatinine level. The SKI HIT variables included prediction-period CKD status, International Society of Nephrology (ISN)/Renal Pathology Society (RPS) class, 12-month proteinuria, 12-month serum creatinine level, race, and an interaction between ISN/RPS class and 12-month proteinuria. The RRT HIT included age at diagnosis, 12-month proteinuria, and 12-month serum creatinine level. Each HIT validated well internally (c-indices 0.84-0.92) and in an independent LN cohort (c-indices 0.89-0.92). CONCLUSION: HITs, derived from short-term kidney responses to treatment, correlate with long-term kidney outcomes, and now must be validated as surrogate end points for LN clinical trials.


Assuntos
Biomarcadores/análise , Nefrite Lúpica/mortalidade , Insuficiência Renal Crônica/mortalidade , Terapia de Substituição Renal/mortalidade , Índice de Gravidade de Doença , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/terapia , Adulto , Fatores Etários , Ensaios Clínicos como Assunto , Creatinina/sangue , Bases de Dados Factuais , Feminino , Humanos , Estudos Longitudinais , Nefrite Lúpica/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Proteinúria/urina , Insuficiência Renal Crônica/terapia , Reprodutibilidade dos Testes
15.
Clin J Am Soc Nephrol ; 13(10): 1502-1509, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089664

RESUMO

BACKGROUND AND OBJECTIVES: Incomplete peripheral blood B cell depletion after rituximab in lupus nephritis might correlate with inability to reduce tubulointerstitial lymphoid aggregates in the kidney, which together could be responsible for inadequate response to treatment. We utilized data from the Lupus Nephritis Assessment with Rituximab (LUNAR) study to characterize the variability of peripheral blood B cell depletion after rituximab and assess its association with complete response in patients with lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed 68 participants treated with rituximab. Peripheral blood B cell depletion was defined as 0 cells/µl, termed "complete peripheral depletion," assessed over 78 weeks. Logistic regression was used to estimate the association between characteristics of complete peripheral depletion and complete response (defined as urine protein-to-creatinine ratio <0.5 mg/mg, and normal serum creatinine or an increase in creatinine <15%, if normal at baseline), assessed at week 78. RESULTS: A total of 53 (78%) participants achieved complete peripheral depletion (0 cells/µl) in a median time of 182 days (interquartile range, 80-339).The median duration of complete peripheral depletion was 71 days (interquartile range, 14-158). Twenty-five (47%) participants with complete peripheral depletion achieved complete response, compared with two (13%) without. Complete peripheral depletion was associated with complete response (unadjusted odds ratio [OR], 5.8; 95% confidence interval [95% CI], 1.2 to 28; P=0.03). Longer time to achieving complete peripheral depletion was associated with a lower likelihood of complete response (unadjusted OR, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Complete peripheral depletion lasting >71 days (the median) was associated with complete response (unadjusted OR, 4.1; 95% CI, 1.5 to 11; P=0.008). CONCLUSIONS: There was substantial variability in peripheral blood B cell depletion in patients with lupus nephritis treated with rituximab from the LUNAR trial. Achievement of complete peripheral depletion, as well as the rapidity and duration of complete peripheral depletion, were associated with complete response at week 78. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_06_CJASNPodcast_18_10_.mp3.

16.
Lupus Sci Med ; 5(1): e000258, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29657738

RESUMO

Formidable impediments stand in the way of treatment development for lupus. These include the unwieldy size of current trials, international competition for scarce patients, complex outcome measures and a poor understanding of these outcomes in the world at large. The heterogeneity of the disease itself coupled to superimposition of variegated background polypharmacy has created enough immunological noise to virtually ensure the failure of lupus treatment trials, leaving an understandable suspicion that at least some of the results in testing failed drugs over the years may not have been negative, but merely uninterpretable. The authors have consulted with many clinical trial investigators, biopharmaceutical developers and stakeholders from government and voluntary sectors. This paper examines the available evidence that supports workable trial designs and proposes approaches to improve the odds of completing interpretable treatment development programs for lupus.

17.
Arthritis Rheumatol ; 69(10): 1996-2005, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28891237

RESUMO

OBJECTIVE: Estimates of the incidence and prevalence of systemic lupus erythematosus (SLE) in the US have varied widely. The purpose of this study was to conduct the California Lupus Surveillance Project (CLSP) to determine credible estimates of SLE incidence and prevalence, with a special focus on Hispanics and Asians. METHODS: The CLSP, which is funded by the Centers for Disease Control and Prevention, is a population-based registry of individuals with SLE residing in San Francisco County, CA, from January 1, 2007 through December 31, 2009. Data sources included hospitals, rheumatologists, nephrologists, commercial laboratories, and a state hospital discharge database. We abstracted medical records to ascertain SLE cases, which we defined as patients who met ≥4 of the 11 American College of Rheumatology classification criteria for SLE. We estimated crude and age-standardized incidence and prevalence, which were stratified by sex and race/ethnicity. RESULTS: The overall age-standardized annual incidence rate was 4.6 per 100,000 person-years. The average annual period prevalence was 84.8 per 100,000 persons. The age-standardized incidence rate in women and men was 8.6 and 0.7 per 100,000 person-years, respectively. This rate was highest among black women (30.5), followed by Hispanic women (8.9), Asian women (7.2), and white women (5.3). The age-standardized prevalence in women per 100,000 persons was 458.1 in blacks, 177.9 in Hispanics, 149.7 in Asians, and 109.8 in whites. Capture-recapture modeling estimated 33 additional incident cases and 147 additional prevalent cases. CONCLUSION: Comprehensive methods that include intensive case-finding provide more credible estimates of SLE in Hispanics and Asians, and confirm racial and ethnic disparities in SLE. The disease burden of SLE is highest in black women, followed by Hispanic women, Asian women, and white women.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/epidemiologia , Sistema de Registros , Adulto , Afro-Americanos/estatística & dados numéricos , Nativos do Alasca/estatística & dados numéricos , Americanos Asiáticos/estatística & dados numéricos , California/epidemiologia , Monitoramento Epidemiológico , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Incidência , Índios Norte-Americanos/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Grupo com Ancestrais Oceânicos/estatística & dados numéricos , Prevalência , São Francisco/epidemiologia
18.
Rheumatol Int ; 37(8): 1249-1255, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28258475

RESUMO

In this study, we aimed to systematically review available literature on the efficacy of eculizumab for the treatment of renal involvement in patients with systemic lupus erythematosus (SLE). We conducted a literature search developed a priori, to identify articles reporting clinical experience with the use of eculizumab in SLE patients, focusing on renal involvement. The search strategy was applied to Ovid MEDLINE, EMBASE, In-Process and Other Non-Indexed Citation, Cochrane Central Register of Controlled Trials and Scopus from 2006 to present. Abstracts from EULAR and ACR congresses were also screened. We included six publications describing the renal outcome in SLE patients receiving eculizumab. Five out of six cases described the occurrence of thrombotic microangiopathy (TMA) in renal biopsies of patients with known SLE; three cases with biopsy-proven lupus nephritis (LN) and two patients with SLE-related antiphospholipid syndrome without histologic evidence of LN. One study reported the outcome of a patient with severe refractory LN successfully treated with eculizumab. All patients, regardless of the presence of concomitant LN, presented with severe hypocomplementemia and renal function impairment. All patients showed a sustained improvement of renal function and normalization of complement parameters after treatment with eculizumab[median follow-up 9 months (1-17)]. Despite the limitations of the currently available evidence, existing data are promising and provide preliminary support for the use of eculizumab in selected cases of SLE with renal involvement, especially in the presence of TMA, or in patients with refractory LN.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Fármacos Renais/administração & dosagem , Microangiopatias Trombóticas/tratamento farmacológico , Lesão Renal Aguda/etiologia , Síndrome Antifosfolipídica/complicações , Feminino , Humanos , Rim/patologia , Nefrite Lúpica/complicações , Nefrite Lúpica/imunologia , Masculino , Microangiopatias Trombóticas/complicações
19.
Curr Opin Rheumatol ; 29(3): 241-247, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28207493

RESUMO

PURPOSE OF REVIEW: Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies. RECENT FINDINGS: Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity. Despite disappointing results of several recent trials, novel therapies targeting diverse immunologic pathways are being actively studied in lupus nephritis. Two promising strategies include the use of B-cell depletion therapy and multitarget therapy with calcineurin inhibitors. In parallel with the conduct of these trials, there are ongoing efforts to improve trial design. Two recent studies of outcome measures reported that a level of proteinuria of less than 0.7-0.8 g at 12 months is most predictive of good long-term renal outcome, and that the inclusion of urine red blood cells worsens the predictive value of proteinuria alone. SUMMARY: Improved understanding of lupus nephritis pathogenesis, development of novel therapies, and optimization of clinical trial design are leading the path forward for successful drug development in lupus nephritis. The ultimate goal of these efforts is to treat our patients in a more strategic, personalized manner that improves long-term outcomes.


Assuntos
Gerenciamento Clínico , Nefrite Lúpica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Linfócitos B/imunologia , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/imunologia
20.
J Immunol ; 197(7): 2854-63, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27534558

RESUMO

The loss of tolerance and the presence of circulating autoantibodies directed against nuclear Ags is the hallmark of systemic lupus erythematosus (SLE). Many of these Ags are complexed with short, noncoding RNAs, such as U1 and Y1. The amount of U1 and Y1 RNA complexed with SLE patient Abs and immune complexes was measured in a cross-section of 228 SLE patients to evaluate the role of these RNA molecules within the known biochemical framework of SLE. The study revealed that SLE patients had significantly elevated levels of circulating U1 and/or Y1 RNA compared with healthy volunteers. In addition, the blood-borne RNA molecules were correlated with SLE disease activity and increased expression of IFN-inducible genes. To our knowledge, this study provides the first systematic examination of the role of circulating RNA in a large group of SLE patients and provides an important link with IFN dysregulation.


Assuntos
Regulação da Expressão Gênica , Interferons/imunologia , Lúpus Eritematoso Sistêmico/genética , RNA/sangue , Adulto , Reações Antígeno-Anticorpo , Autoanticorpos/imunologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , RNA/imunologia , RNA Citoplasmático Pequeno/sangue , RNA Nuclear Pequeno/sangue
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