Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5- CD11c+ cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased Toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7. DN2 cells shared with activated naive cells (aNAV), phenotypic and functional features, and similar transcriptomes. Their PC differentiation and autoantibody production was driven by TLR7 in an interleukin-21 (IL-21)-mediated fashion. An in vivo developmental link between aNAV, DN2 cells, and PC was demonstrated by clonal sharing. This study defines a distinct differentiation fate of autoreactive naive B cells into PC precursors with hyper-responsiveness to innate stimuli, as well as establishes prominence of extra-follicular B cell activation in SLE, and identifies therapeutic targets.

Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Financial Hardship and Sleep Quality Among Black American Women With and Without Systemic Lupus Erythematosus.

OBJECTIVE: To compare dimensions of financial hardship and self-reported sleep quality among Black women with versus without systemic lupus erythematosus (SLE). METHODS: Participants were 402 Black women (50% with validated diagnosis of SLE) living in Georgia between 2017 and 2020. Black women with SLE were recruited from a population-based cohort established in Atlanta, and Black women without SLE were recruited to be of comparable age and from the same geographic areas as SLE women. Financial hardship was measured using three different scales: financial adjustments, financial setbacks, and financial strain. Sleep was assessed continuously using the Pittsburgh Sleep Quality Index (PSQI) scale. Each dimension of financial hardship was analyzed separately in SLE-stratified multivariable linear regression models and adjusted by sociodemographic and health status factors. RESULTS: Dimensions of financial hardship were similarly distributed across the two groups. Sleep quality was worse in Black women with, versus without, SLE (p < .001). Among Black women with SLE, financial adjustment was positively associated with a 0.40-unit increase in poor sleep quality (95% CI = 0.12-0.67, p = .005). When accounting for cognitive depressive symptoms, financial setbacks and strain were somewhat attenuated for Black women with SLE. Overall, no associations between financial hardships and sleep quality were observed for the women without SLE. CONCLUSIONS: Black women with SLE who experience financial hardships may be more at risk for poor sleep quality than Black women without SLE. Economic interventions targeting this population may help improve their overall health and quality of life.

The impact of social determinants of health on the presentation, management and outcomes of systemic lupus erythematosus.

Disparities in SLE rates and outcomes have been attributed to genetic and hormonal factors, cigarette smoking and environmental pollutants. However, a growing body of research indicates that social determinants of health (SDH) also have substantial impact on the disparities that characterize SLE. According to the World Health Organization, SDH are defined as 'the conditions in which people are born, grow, work, live, and age', account for 30-55% of health outcomes, and adversely impact health outcomes among those of low socioeconomic status and stigmatized racial/ethnic groups. We reviewed the impact of key SDH on SLE presentation, management and outcomes, including income, education, neighbourhood factors, healthcare access, discrimination and social support. We found that adverse SDH conditions may lead to more severe SLE with increased morbidity and mortality, and that SDH affect SLE management by dictating the most feasible monitoring and treatment plan for each individual patient based on his or her specific life circumstances (for example, based on health insurance status, distance to nearest provider and/or drug affordability). SDH also have a significant impact on SLE outcomes, with worse disease and psychosocial outcomes associated with lower income level, lower educational attainment, disadvantaged neighbourhoods, lack of health insurance or public health insurance in the USA, travel burden to nearest provider, anti-Black racism and lower social support. Future efforts to improve the management and outcomes of patients with SLE must combat the societal, economic and political forces that perpetuate these inequities.

Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities.

OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

B cell subset composition segments clinically and serologically distinct groups in chronic cutaneous lupus erythematosus.

OBJECTIVE: While the contribution of B-cells to SLE is well established, its role in chronic cutaneous lupus erythematosus (CCLE) remains unclear. Here, we compare B-cell and serum auto-antibody profiles between patients with systemic lupus erythematosus (SLE), CCLE, and overlap conditions. METHODS: B-cells were compared by flow cytometry amongst healthy controls, CCLE without systemic lupus (CCLE+/SLE-) and SLE patients with (SLE+/CCLE+) or without CCLE (SLE+/CCLE-). Serum was analyed for autoreactive 9G4+, anti-double-stranded DNA, anti-chromatin and anti-RNA antibodies by ELISA and for anti-RNA binding proteins (RBP) by luciferase immunoprecipitation. RESULTS: Patients with CCLE+/SLE- share B-cell abnormalities with SLE including decreased unswitched memory and increased effector B-cells albeit at a lower level than SLE patients. Similarly, both SLE and CCLE+/SLE- patients have elevated 9G4+ IgG autoantibodies despite lower levels of anti-nucleic acid and anti-RBP antibodies in CCLE+/SLE-. CCLE+/SLE- patients could be stratified into those with SLE-like B-cell profiles and a separate group with normal B-cell profiles. The former group was more serologically active and more likely to have disseminated skin lesions. CONCLUSION: CCLE displays perturbations in B-cell homeostasis and partial B-cell tolerance breakdown. Our study demonstrates that this entity is immunologically heterogeneous and includes a disease segment whose B-cell compartment resembles SLE and is clinically associated with enhanced serological activity and more extensive skin disease. This picture suggests that SLE-like B-cell changes in primary CCLE may help identify patients at risk for subsequent development of SLE. B-cell profiling in CCLE might also indentify candidates who would benefit from B-cell targeted therapies.

Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.

OBJECTIVES: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in 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 high-density lipoprotein (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.

Anticipatory racism stress, smoking and disease activity: the Black women's experiences living with lupus (BeWELL) study.

African American women with systemic lupus erythematosus (SLE) have worse disease outcomes compared to their White counterparts. Stressors associated with race may contribute to poorer health in this population through maladaptive behavioral pathways. This study investigated relationships between stress associated with anticipating racism, smoking, and SLE disease activity. Data were from 432 African American women with SLE in the Black Women's Experiences Living with Lupus (BeWELL) Study. Controlling for sociodemographic and health-related covariates, multivariable regression analyses revealed a significant association between anticipatory racism stress (ARS) and disease activity (p = 0.00, b = 1.13, 95% CI [0.43, 1.82]). A significant interaction between ARS and smoking also indicated that smoking exacerbated the effect of ARS on disease activity (p = 0.04, b = 1.95, CI = 0.04, 3.96). Test for evidence of smoking mediating the effect of ARS on disease activity were not statistically significant (z = 1.77, p = 0.08). Findings have implications for future SLE disparities research among African American women with SLE.

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus.

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.

Racial Discrimination, Disease Activity, and Organ Damage: The Black Women's Experiences Living With Lupus (BeWELL) Study.

Black women are disproportionately affected by systemic lupus erythematosus (SLE), a chronic, potentially debilitating autoimmune disease, and they also experience more rapid progression and worse outcomes compared with other groups. We examined if racial discrimination is associated with disease outcomes among 427 black women with a validated diagnosis of SLE, who live in the Atlanta, Georgia, metropolitan area, and were recruited to the Black Women's Experiences Living with Lupus Study (2015-2017). Frequency of self-reported experiences of racial discrimination in domains such as employment, housing, and medical settings was assessed using the Experiences of Discrimination measure. SLE activity in the previous 3 months, including symptoms of fatigue, fever, skin rashes, and ulcers, was measured using the Systemic Lupus Activity Questionnaire; irreversible damage to an organ or system was measured using the Brief Index of Lupus Damage. Results of multivariable linear regression analyses examining the Systemic Lupus Activity Questionnaire and log-transformed Brief Index of Lupus Damage scores indicated that increasing frequency of racial discrimination was associated with greater SLE activity (b = 2.00, 95% confidence interval: 1.32, 2.68) and organ damage (b = 0.08, 95% confidence interval: 0.02, 0.13). Comprehensive efforts to address disparities in SLE severity should include policies that address issues of racial discrimination.

Update on lupus epidemiology: advancing health disparities research through the study of minority populations.

PURPOSE OF REVIEW: The current review focuses on recent population-based studies that have examined the burden of lupus, disease outcomes, and gaps in quality of care, with an emphasis in research addressing health disparities. RECENT FINDINGS: The Centers for Disease Control and Prevention National Lupus Registries underscored higher susceptibility of both systemic lupus erythematosus (SLE) and primary cutaneous lupus among people of color, compared with whites. Not only does SLE disproportionately strike people from racial and ethnic minorities, those individuals are also at increased risk of developing severe manifestations following SLE diagnosis. Mortality is higher and death occurs at a younger age among blacks, compared with whites. Furthermore, ongoing Centers for Disease Control and Prevention-supported population-based lupus cohorts, along with research by other groups, have provided new insight into the role of social determinants on outcomes and opportunities to improve care in diverse lupus populations. SUMMARY: While descriptive epidemiological efforts have been critical to providing more accurate estimates of the burden and mortality of lupus across diverse demographic groups, emerging research suggests a significant influence of psychosocial and healthcare system factors on disease outcomes. These current efforts represent important steps toward the development of clinical and public health interventions aimed at eliminating health disparities in lupus populations.

Relationships among organ damage, social support, and depression in African American women with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) disproportionately strikes African American women. Social support can potentially reduce disease impact. The purpose of this study is to understand the relationship between organ damage and depression in African American women and how social support influences this relationship. METHODS: We used a mixed methods design, analyzing self-reported data on lupus-related organ damage, depression, and social support in 437 African American women with SLE recruited in the Georgians Organized Against Lupus (GOAL) cohort. Moreover, we conducted interviews among 15 GOAL participants to gather patients' perspectives about the role of social support in people who live with lupus. RESULTS: We found a significant association between organ damage and depression ( r = 0.163, p = 0.001), as well as between depression and social support ( F = 17.574, p < 0.001). The quantitative analysis did not render social support as a significant moderator in the organ damage-depression relationship. Interviews, however, revealed that African American women with the most severe organ damage have the greatest need for support. CONCLUSIONS: Social support is a key resource for lupus patients with high disease burden. Overall, these findings highlight the importance of monitoring depressive symptoms in this population and developing interventions aimed to increase social support available to lupus patients.

Racial Disparities in Mortality Associated with Systemic Lupus Erythematosus - Fulton and DeKalb Counties, Georgia, 2002-2016.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with often nonspecific symptoms that can lead to a delay in diagnosis. The disease disproportionately affects women and minorities. Blacks with SLE also have more severe disease and develop it at an earlier age (1). Despite an increase in the 5-year survival rate from 50% in 1955 to approximately 90% in the 2000s, attributed largely to advances in management of SLE (2), premature mortality among SLE patients persists, often as a result of disease severity, infections, and cardiovascular disease. Because existing SLE mortality estimates based on death certificate data are known to underestimate SLE deaths (3), SLE mortality was analyzed using 2002-2004 data from the population-based Georgia Lupus Registry (1). Incident and prevalent SLE cases matched to the National Death Index through 2016 identified 97 and 401 deaths, respectively. Standardized mortality ratios adjusted for age group, sex, and race were two to three times higher among persons with SLE relative to expected deaths in the general population. Blacks had significantly higher cumulative mortality than did whites, and blacks with both incident and prevalent cases were significantly younger at death (mean age 51.8 and 52.3 years, respectively) than were whites (mean age 64.4 and 65.0 years, respectively). Whites had lower mortality after diagnosis than did blacks; among incident cases, mortality among whites did not occur until 5 years after SLE diagnosis, whereas blacks had significantly and persistently higher mortality from the time of diagnosis. There were no significant differences by sex. Current CDC-supported efforts encourage early detection, diagnosis, and treatment, and enhanced self-management skills to mitigate racial disparities and improve outcomes overall among persons with SLE.

Depressive Symptoms Are Associated With Low Treatment Adherence in African American Individuals With Systemic Lupus Erythematosus.

OBJECTIVE: African American (AA) people with systemic lupus erythematosus (SLE) are at high morbidity and mortality risk, and they often require multiple medications. Low medication adherence is a highly prevalent, multidimensional problem associated with poor outcomes in people with SLE. Depression, a predictor of low adherence in people with chronic conditions, has been described in over 35% of AAs with SLE. We hypothesized that depressive symptoms would be increasingly associated with low adherence in this population. METHODS: Research subjects predominantly belong to the Georgians Organized Against Lupus cohort, a population-based cohort of predominantly AA individuals with SLE in the Atlanta metropolitan area. Medication adherence and severity of depressive symptoms were measured using validated self-reported tools: the 8-item Morisky Medication Adherence Scale and the 9-item Patient Health Questionnaire, respectively. We used univariate and multivariate logistic regression to examine the odds ratios of low medication adherence across individuals with increasing severity of depressive symptoms. RESULTS: Among 632 AA SLE participants, 336 (54%) reported low medication adherence and 217 (34.6%) reported "moderate" or "severe" depressive symptoms. In univariate logistic regression, significant risk factors for low adherence were depressive symptoms, low self-efficacy, poor satisfaction with care, female sex, younger age, hurried patient-physician communication, poorer shared decision-making, less compassionate physician communication style, poor/fair health, and higher disease activity score. In multivariate regression, younger age, female sex, and more severe depressive symptoms were associated with low medication adherence. CONCLUSIONS: This is the first study to examine factors associated with low medication adherence among a population-based cohort of AA individuals with SLE. Depression was a strong correlate of low medication adherence. Mental health interventions aiming to address and treat depression may increase medication adherence.

The frequency and outcome of lupus nephritis: results from an international inception cohort study.

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.

Comparison of vascular access outcomes in patients with end-stage renal disease attributed to systemic lupus erythematosus vs. other causes: a retrospective cohort study.

BACKGROUND: U.S. hemodialysis patients with systemic lupus erythematosus (SLE) and end-stage renal disease (ESRD) are less likely than other ESRD patients to have a permanent vascular access (fistula or graft) in place at the dialysis start. We examined whether vascular access outcomes after dialysis start differed for SLE vs. other ESRD patients. METHODS: Among U.S. patients initiating hemodialysis in 2010 with only a catheter (n = 40,911; 384 with SLE) and using a permanent access on first dialysis (n = 13,073; 48 with SLE), we examined the association of SLE status with time to first placement of a permanent access (among catheter-only patients) and to loss of access patency (among patients using a permanent access on first dialysis), both censored 1 year after dialysis start, using multivariable Cox proportional hazards models. RESULTS: Among catheter-only patients, 46.1 % vs. 54.5 % of those with SLE-ESRD vs. other ESRD had a permanent access placed within 1 year after dialysis start. However, with adjustment, there was no association of 1-year placement with SLE status [HR = 1.00 (95 % CI, 0.86-1.17)]. SLE-ESRD vs. other ESRD patients starting dialysis with a permanent access were less likely to experience a 1-year loss of patency (43.8 % vs. 55.0 %), but this association was not statistically significant after adjustment [HR = 0.88 (0.57-1.37)]. CONCLUSION: These results suggest that SLE-ESRD patients starting dialysis with a catheter are not more likely to have a permanent access placed in the first year of dialysis, despite an observed lack of association of SLE status with subsequent loss of vascular access patency among those starting dialysis with a permanent access.

Epidemiology of lupus: an update.

PURPOSE OF REVIEW: Recent interest in lupus has expanded various efforts to better define its population burden. The Centers for Disease Control and Prevention coordinated National Lupus Registries that advance our epidemiologic understanding of and methodological approach to lupus. RECENT FINDINGS: More accurate estimates of incidence and prevalence of lupus in the United States have shown significant burden among racial/ethnic minority groups. These efforts underscore the need to better coordinate future studies, particularly as it relates to case definition. SUMMARY: These efforts confirm the significant burden of systemic lupus erythematosus, particularly in younger minority populations. Experience from these studies could also inform other surveillance efforts in lupus, as well as other medical conditions for which similar methodologic challenges exist.

Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort.

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.

Discrimination and Cumulative Disease Damage Among African American Women With Systemic Lupus Erythematosus.

OBJECTIVES: We examined associations between unfair treatment, attributions of unfair treatment to racial discrimination, and cumulative disease damage among African American women with systemic lupus erythematosus (SLE). METHODS: We used multivariable regression models to examine SLE damage among 578 African American women in metropolitan Atlanta, Georgia, recruited to the Georgians Organized Against Lupus cohort. RESULTS: When we controlled for demographic, socioeconomic, and health-related covariates, reporting any unfair treatment was associated with greater SLE damage compared with reporting no unfair treatment (b = 0.55; 95% confidence interval = 0.14, 0.97). In general, unfair treatment attributed to nonracial factors was more strongly associated with SLE damage than was unfair treatment attributed to racial discrimination, although the difference was not statistically significant. CONCLUSIONS: Unfair treatment may contribute to worse disease outcomes among African American women with SLE. Unfair treatment attributed to nonracial causes may have a more pronounced negative effect on SLE damage. Future research may further examine possible differences in the effect of unfair treatment by attribution.