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1.
MMWR Morb Mortal Wkly Rep ; 70(7): 236-239, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33600382

RESUMO

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with manifestations that vary widely in severity. Although minority populations are at higher risk for SLE and have more severe outcomes (1), population-based estimates of mortality by race and ethnicity are often lacking, particularly for Asian and Hispanic/Latino persons. Among 812 patients in the California Lupus Surveillance Project (CLSP) during 2007-2009 (2,3), who were matched to the 2007-2017 National Death Index (NDI), 16.6% had died by 2017. This proportion included persons of White (14.4%), Black (25%), Asian (15.3%), and Hispanic/Latino (15.5%) race/ethnicity. Standardized mortality ratios (SMRs) of observed-to-expected deaths among persons with SLE within each racial/ethnic group were 2.3, 2.0, 3.8, and 3.9, respectively. These findings provide the first population-based estimates of mortality among Asian and Hispanic/Latino persons with SLE. Coordination of robust care models between primary care providers and rheumatologists could ensure that persons with SLE receive a timely diagnosis and appropriate treatments that might help address SLE-associated mortality.


Assuntos
Americanos Asiáticos/estatística & dados numéricos , Hispano-Americanos/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/mortalidade , Grupos Minoritários/estatística & dados numéricos , Adolescente , Adulto , Idoso , California/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/etnologia , Adulto Jovem
2.
Arthritis Rheumatol ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33474834

RESUMO

OBJECTIVE: Epidemiologic data for systemic lupus erythematosus (SLE) is limited, particularly for racial/ethnic subpopulations in the United States (U.S.). Leveraging data from the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, a meta-analysis estimating U.S. SLE prevalence was performed. METHODS: The CDC National Lupus Registry network included four registries in unique states and a fifth in the Indian Health Service (IHS). All registries used the 1997 revised American College of Rheumatology (ACR) classification criteria for the SLE case definition. Case finding spanned either 2002-2004 or 2007-2009. A random effects model was employed given heterogeneity across sites. Applying sex/race-stratified estimates to the 2018 Census population, an estimate for the number of SLE cases in the U.S. was generated. RESULTS: 5,417 cases fulfilled the ACR SLE classification criteria. Pooled prevalence from the four state-specific registries was 72.8/100,000 (95%CI:65.3,81.0), 9 times higher for females than males (128.7 vs 14.6), and highest among Black females (230.9), followed by Hispanic (120.7), white (84.7) and Asian/Pacific Islander females (84.4). Male prevalence was highest in Black males (26.7) followed by Hispanic (18.0), Asian/Pacific Islander (11.2), and white males (8.9). The American Indian/Alaska Native had the highest race-specific SLE estimates for females (270.6/100,000) and males (53.8/100,000). In 2018, 204,295 persons (95% CI:160,902,261,725) in the U.S. fulfilled ACR SLE classification criteria. CONCLUSIONS: A coordinated network of population-based SLE registries provided more accurate estimates for SLE prevalence and numbers affected in the U.S.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33421358

RESUMO

OBJECTIVE: Physical activity is known to improve depressive symptoms, but this is the first study to examine physical inactivity as a predictor of incident depression in systemic lupus erythematosus (SLE). METHODS: Data derive from the California Lupus Epidemiology Study (CLUES), a longitudinal cohort with confirmed SLE diagnoses. Physical inactivity was assessed from a single item, "I rarely or never do any physical activities", and depressive symptoms by the Patient Health Questionnaire (PHQ-8). Analysis included those not depressed at baseline (PHQ-8 <10) who completed an in-person baseline assessment and at least one follow-up visit (n=225). Incident depression was defined as PHQ-8 ≥10 at follow-up. Cox proportional hazards regression modeled incident depression over 2 years as a function of baseline physical inactivity, controlling for age, sex, race, income, comorbidities, disease activity, and disease damage. RESULTS: At baseline, the mean age was 45±15, 88% were female, and 70% identified as non-white. Mean PHQ scores for those without depression at baseline did not differ by activity status, but those who were inactive at baseline were significantly more likely to develop depression over the next two years (HR=2.89, 95% CI=1.46, 5.71). After adjusting for covariates, the association remained strong, including a greater than 3-fold increased risk of incident depression among the sedentary group (HR=3.88; 95% CI=1.67, 9.03). CONCLUSION: In this diverse SLE cohort, a simple question about physical inactivity was highly predictive of incident depression over the subsequent 2 years. Results suggest an urgent need for approaches to reduce sedentary behavior in this high-risk population.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33337580

RESUMO

OBJECTIVE: Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asians is lacking. We examined SLE disease activity, severity, and damage among Asians of primarily Chinese and Filipino descent in a multiethnic cohort. METHODS: California Lupus Epidemiology Study (CLUES, n=328) data were analyzed. Data were collected in English, Cantonese, Mandarin or Spanish, using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]) and disease damage (Systemic Lupus International Collaborating Clinics Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. RESULTS: Asians were the largest racial/ethnic group (38%; [Chinese=22%; Filipino=9%; Other=7%]). Average age at diagnosis (years) was younger among Asians (27.9), particularly Filipinos (22.2), compared with Whites (29.4) and Blacks (34.0). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asians was significantly higher than Whites (LSI 7.1 vs 6.5; p<0.05) but similar to Blacks and Hispanics. Early age at diagnosis was associated with greater organ damage among Asians, Blacks, and Hispanics, but not Whites. CONCLUSIONS: SLE was more severe among US Asians compared to Whites. Filipinos were affected at strikingly young ages. Asians and non-White groups with younger age at diagnosis had greater organ damage than Whites. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asians with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33026693

RESUMO

Non-white people are more likely to develop systemic lupus erythematosus (SLE), yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non-white populations. To address these issues, a conference was held in Bethesda, Maryland from October 15th -16th , 2019 entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and United States government representatives (the Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all of these groups, the organizers purposefully included people of non-white ancestry. Decreased participation of non-white SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non-white patient participation in SLE and non-SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies.

6.
Arthritis Rheumatol ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32755035

RESUMO

OBJECTIVE: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN). METHODS: In a multicenter, randomized, open-label clinical trial, 43 patients with recurrent or refractory LN were treated with rituximab, cyclophosphamide (CYC), and glucocorticoids followed by weekly belimumab infusions until week 48 (RCB group) or with rituximab and CYC but no belimumab infusions (RC group). Patients were followed up until week 96. Percentages of total and autoreactive B cell subsets in the patients' peripheral blood were analyzed by flow cytometry. RESULTS: Treatment with belimumab did not increase the incidence of adverse events in patients with refractory LN. At week 48, a complete or partial renal response occurred in 11 (52%) of 21 patients receiving belimumab, compared to 9 (41%) of 22 patients in the RC group who did not receive belimumab (P = 0.452). Lack of improvement in or worsening of LN was the major reason for treatment failure. B cell depletion occurred in both groups, but the percentage of B cells remained lower in those receiving belimumab (geometric mean number of B cells at week 60, 53 cells/µl in the RCB group versus 11 cells/µl in the RC group; P = 0.0012). Percentages of total and autoreactive transitional B cells increased from baseline to week 48 in both groups. However, percentages of total and autoreactive naive B cells decreased from baseline to week 48 in the belimumab group compared to the no belimumab RC group (P = 0.0349), a finding that is consistent with impaired maturation of naive B cells and enhanced censoring of autoreactive B cells. CONCLUSION: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN. This regimen diminished maturation of transitional to naive B cells during B cell reconstitution, and enhanced the negative selection of autoreactive B cells. Clinical efficacy was not improved with rituximab and CYC in combination with belimumab when compared to a therapeutic strategy of B cell depletion alone in patients with LN.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32741118

RESUMO

OBJECTIVE: Health disparities in patient-reported outcomes (PROs) by income and education are well documented; the impact of health literacy on PROs has received less attention. We examined independent effects of income, education, and health literacy on PROs in SLE. METHODS: Data from the California Lupus Epidemiology Study (CLUES, n=323) were used. Health literacy was assessed with a validated 3-item measure (ability to understand written information, reliance on others to understand written information, confidence in completing written forms). PROs were administered by interview in English, Spanish, Cantonese, or Mandarin. Generic and disease-specific PROs were examined: ten PROMIS short forms, the eight SF-36 subscales, and three patient-reported SLE disease activity and damage measures. We conducted two sets of multivariable analyses: the first examined education, income, or health literacy individually; the second included all three simultaneously. All multivariable models included age, sex, race/ethnicity, language, disease duration, and physician-assessed disease activity and damage. RESULTS: Over one-third (38%) had limited health literacy (LHL), including >25% with greater than high school education. In multivariable analyses simultaneously considering education, income, and health literacy, LHL was associated with significantly worse scores on all PROs except disease damage. In contrast, disparities by income were seen in only three PROMIS scales, three SF-36 subscales, and one disease activity measure. No disparities by education level were noted. CONCLUSIONS: We found significantly worse PRO scores among individuals with LHL, even after controlling for disease activity and damage. Whether disparities are due to actual differences in health or measurement issues requires further study.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32741124

RESUMO

OBJECTIVE: Health-related quality of life (HRQoL) is reduced in systemic lupus erythematosus (SLE), partly driven by comorbid depression. Among patients with SLE, the association between major depression and HRQoL, measured using the NIH's Patient-Reported Outcomes Measurement Information System (PROMIS), is not well characterized. The objective was to determine an association between major depression and HRQoL as measured by PROMIS. METHODS: Cross-sectional data were obtained from the California Lupus Epidemiology Study, a cohort of adults in the San Francisco Bay Area with SLE. We studied the association between major depression (score ≥10 on the Patient Health Questionnaire 8 depression scale) and T scores (scaled to population mean ± SD of 50 ± 10) on 12 PROMIS domains representing physical, mental, and social health. Mean T scores in depressed and nondepressed individuals were compared using multiple linear regression models adjusting for age, sex, race/ethnicity, disease activity, damage, body mass index, and household income. RESULTS: Mean age of the 326 participants was 45 years; ~89% were women, 29% White, 23% Hispanic, 10% African American, and 36% Asian. One-fourth met the criteria for major depression. In multivariable analyses, major depression was independently associated with worse T scores on all 12 PROMIS domains (P < 0.001); compared with those without major depression, depressed individuals scored >10 points (1 SD) worse on fatigue, sleep impairment, negative psychosocial impact of illness, satisfaction in discretionary social activities, and satisfaction in social roles. CONCLUSION: In individuals with SLE, major depression is associated with markedly worse PROMIS scores in physical, mental, and social domains. Diagnosing and treating depression may help improve HRQoL in individuals with SLE.

10.
Am J Pharm Educ ; 84(2): 847519, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32226076

RESUMO

Objective. To develop and evaluate a mobile learning module to support knowledge construction between medical and pharmacy students through structured dialogue prompts. Methods. Rheumatologists and pharmacists collaboratively developed a two-week, case-based, asynchronous interprofessional learning module that was delivered via a mobile app and focused on collaborative medication management of a complex case involving a patient with systemic lupus erythematosus. The clinical case evolved over three phases: diagnosis, initial treatment, and medication-related complications. Dialogue prompts were incorporated in each phase as a mechanism to support knowledge construction among learners. Pharmacy and medical student pairs were randomized to receive either high guidance or low guidance prompts for collaborative learning. The student pairs worked together, asynchronously, online, to develop three collaborative care plans. The evaluation of the learning module to support knowledge construction included: analysis of text-based dialogue coded for knowledge construction phases; the accuracy and completeness of the three collaborative care plans; and quantitative and qualitative participant feedback. Results. Sixteen pairs of medical and pharmacy students (n=32) participated. Pairs who received high guidance engaged in all phases of knowledge construction more often than pairs who received low guidance. Guidance phase did not differentially impact collaborative care plan scores. Ninety-eight percent of students agreed or strongly agreed that the module improved their clinical reasoning, interprofessional communication, and knowledge of systemic lupus erythematosus. Conclusion. The knowledge construction framework can guide the design and evaluation of educational interventions such as a mobile learning module to support knowledge construction among health professionals.

12.
ACR Open Rheumatol ; 2(1): 53-60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31943975

RESUMO

OBJECTIVE: Examinations of Patient-Reported Outcomes Measurement Information System (PROMIS) measures in adult systemic lupus erythematosus (SLE) have provided support for their cross-sectional validity in SLE. We estimated responsiveness to change, meaningful changes (minimally important differences [MIDs]), and the patient acceptable symptom state (PASS) for five PROMIS short forms to facilitate longitudinal use and interpretation of PROMIS scales in SLE. METHODS: Data from five administrations of PROMIS short forms in the FORWARD SLE cohorts were used. Pearson correlation coefficients were used to assess associations between changes in PROMIS measures and changes in anchor measures for responsiveness analyses. Worse, same, or better groups were defined for each anchor. Differences in PROMIS scores were calculated for each consecutive PROMIS administration; mean changes in PROMIS scores of individuals in the worse, same, and better groups were calculated. Both anchor-based and distribution-based methods were used to estimate MIDs. PASS was defined as the 75th-percentile positive score among those who considered their health to be acceptable or who were somewhat or very satisfied with their health. RESULTS: All PROMIS short forms showed adequate responsiveness to changes in related patient-reported outcomes. However, only the fatigue and pain interference scales were responsive to self-reported SLE activity. Taking into account all methods, we estimated MIDs for each scale to be approximately two points. All PASS values were better than the population mean T-score of 50. CONCLUSION: These results support use and further study of PROMIS short forms in SLE and should facilitate interpretation of PROMIS scores and changes.

13.
Arthritis Care Res (Hoboken) ; 72(5): 622-629, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31115180

RESUMO

OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with systemic lupus erythematosus (SLE) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to analyze racial and ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: A total of 724 patients with SLE were retrospectively identified. Prevalence ratios (PRs) 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 regression models to estimate hazard ratios (HRs). White patients were the referent group in all analyses. RESULTS: African Americans, Asian/Pacific Islanders, and Hispanic patients had increased prevalence of renal manifestations (PR 1.74 [95% confidence interval (95% CI) 1.40-2.16], PR 1.68 [95% CI 1.38-2.05], and PR 1.35 [95% CI 1.05-1.74], respectively). Furthermore, African Americans had increased prevalence of neurologic manifestations (PR 1.49 [95% CI 1.12-1.98]), and both African Americans (PR 1.09 [95% CI 1.04-1.15]) and Asian/Pacific Islanders (PR 1.07 [95% CI 1.01-1.13]) had increased prevalence of hematologic manifestations. African Americans, Asian/Pacific Islanders, and Hispanic patients, 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], and 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], and HR 2.2 [95% CI 1.1-4.7]). Asian/Pacific Islander and Hispanic patients had higher risk of developing antiphospholipid syndrome (HR 2.5 [95% CI 1.4-4.4] and HR 2.6 [95% CI 1.3-5.1], respectively). CONCLUSION: This is the first epidemiologic study comparing lupus manifestations among 4 major racial and ethnic groups. We found substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups and discovered that African Americans, Asian/Pacific Islanders, and Hispanic patients are at increased risk of developing several severe manifestations following a diagnosis of SLE.


Assuntos
Grupos de Populações Continentais , Grupos Étnicos , Disparidades nos Níveis de Saúde , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , California/epidemiologia , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etnologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Prognóstico , Fatores Raciais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
14.
Rheumatology (Oxford) ; 59(7): 1505-1513, 2020 07 01.
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.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/imunologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lovastatina/uso terapêutico , Adulto , Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Arthritis Care Res (Hoboken) ; 72(7): 888-896, 2020 07.
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 across 25 different clinical sites to identify gaps in quality of care. METHODS: Data from 250 participants with lupus were analyzed across 3 sources (medical records, physician examination, and patient interviews). Overall performance on 8 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% underwent screening laboratory tests for nephritis, 38% underwent lupus activity serum studies, and 81% had their 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.


Assuntos
Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Garantia da Qualidade dos Cuidados de Saúde , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Arthritis Care Res (Hoboken) ; 72(4): 525-533, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31069933

RESUMO

OBJECTIVE: Adverse childhood experiences (ACEs) are associated with poor adult health and immune dysregulation. The impact of ACEs on patients with autoimmune disease is unknown. The present study was undertaken to compare the prevalence of ACEs in patients with systemic lupus erythematosus (SLE) to a population-based survey estimate and to investigate relationships between ACEs and SLE outcomes. METHODS: Data derived from the California Lupus Epidemiology Study (CLUES), a sample of adult patients with SLE. Participants completed a 10-item ACE questionnaire covering 3 domains (abuse, neglect, household challenges). We estimated ACE prevalence in 269 CLUES participants compared to geographically matched respondents from the 2015 California Behavioral Risk Factor Surveillance System (BRFSS), which was standardized to CLUES participant characteristics (age, sex, race/ethnicity). We examined associations of patient-reported and physician-assessed health status measures with overall ACE levels and domains using multivariable linear regression, controlling for sociodemographics, nephritis, and juvenile-onset SLE. RESULTS: Although 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, and without college degrees, but not in those 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. CONCLUSION: 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.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Afro-Americanos , Fatores Etários , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Inquéritos e Questionários
18.
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.


Assuntos
Biologia Computacional , Grupos Étnicos/genética , Genômica , Lúpus Eritematoso Sistêmico/genética , Família Multigênica , Estudos de Coortes , Metilação de DNA , Epigenômica , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Locos de Características Quantitativas , Índice de Gravidade de Doença , Estados Unidos
19.
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
20.
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.

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