Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10−8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.

Objective. To characterize sleep complaints in women with systemic lupus erythematosus (SLE) and to identify correlates of sleep quality. Methods. Sleep quality in 100 women with SLE was assessed using the Pittsburgh Sleep Quality Index (PSQI). Participants completed standardized questionnaires assessing depressed mood, leisure time physical activity, functional disability, and pain severity. A clinical examination determined disease activity, cumulative damage, and whether patients fulfilled the American College of Rheumatology criteria for fibromyalgia. A series of hierarchical multiple regressions were computed. Results. The mean ؎ SD global PSQI score was 6.98 ؎ 4.03, with moderate to severe sleep impairment reported by 56% of the sample. The first model testing the importance of demographic factors was not statistically significant. In the disease-related model, the use of prednisone and functional disability both contributed to poor sleep quality (P < 0.001). The addition of level of exercise participation to the demographic set significantly added to the model (P ‫؍‬ 0.001). Depression significantly added to the demographic set, explaining 29% of the variance (P < 0.0001). When these variables, along with disease related variables, were simultaneously regressed on the PSQI Global Score, only depressed mood appeared as a significant independent determinant of global sleep quality (P < 0.001). However, the point estimates for the Beta coefficients were consistent with effects for lack of exercise and prednisone use. Conclusion. A significant proportion of women with SLE suffer from poor sleep quality. The findings suggest that depressed mood, prednisone use, and lack of exercise contribute to decreased overall sleep quality.

In observational studies, particularly with administrative databases, SLE incidence and prevalence estimates differ considerably, according to the approach for case ascertainment. In the absence of gold standards, statistical modelling can provide sensitivity and specificity estimates for different approaches.

BackgroundSystemic lupus erythematosus (SLE) is a chronic disease of unclear etiology, characterized by an overactive immune system and the production of antibodies that may target normal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly in women.ObjectiveOur aim was to evaluate the potential influence of particulate matter (PM) air pollution on clinical aspects of SLE.MethodsWe studied a clinic cohort of SLE patients living on the island of Montreal, followed annually with a structured clinical assessment. We assessed the association between ambient levels of fine PM [median aerodynamic diameter ≤ 2.5 μm (PM2.5)] measured at fixed-site monitoring stations and SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K), which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renal tubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regression models that we adjusted for daily ambient temperatures and ozone levels.ResultsWe assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000 through 2007 (mean age at time of first visit, 41.2 years). PM2.5 levels were associated with anti-dsDNA and cellular casts. The crude and adjusted odds ratios (reflecting a 10-μg/m3 increase in PM2.5 averaged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65] and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28 (0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM2.5 levels.ConclusionsWe provide novel data that suggest that short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans. Our results add weight to concerns that pollution may be an important trigger of inflammation and autoimmunity.

Objective. Systemic lupus erythematosus (SLE) is characterized by a markedly elevated risk for coronary heart disease (CHD), the exact pathogenesis of which is unknown. In particular, the causal roles of corticosteroid therapy and SLE disease activity, and whether their putative effects are mediated through conventional risk factors, remain unclear.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).

These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.