J Su

Lack of association between the interferon-α signature and longitudinal changes in disease activity in systemic lupus erythematosus

Objective: To study the longitudinal expression of interferon (IFN)-inducible genes in systemic lupus erythematosus (SLE) and determine their suitability as disease biomarkers. Methods: RNA was isolated from the peripheral blood of 94 patients with SLE and 11 controls and reverse transcribed into cDNA. The expression levels of five IFN-responsive genes (LY6E, OAS1, IFIT1, ISG15 and MX1) were determined by quantitative PCR, normalised to GAPDH and summed to generate a global IFN score. Patients were followed longitudinally for a period of 3–12 months, and the association between disease activity, as measured by the SLE disease activity index (SLEDAI-2K), and other clinical and laboratory variables was examined. Results: The expression of all five IFN-responsive genes was significantly higher in patients with SLE than in controls. The expression of LY6E, OAS1, IFIT1 and the global IFN score was associated with high disease activity. The global IFN score was also associated with active renal disease, a decreased C3, and the presence of anti-dsDNA or anti-RNA binding protein antibodies at a single point in time. However, there was a poor correlation between changes in this score and changes in disease activity, C3 or anti-dsDNA antibody levels in patients followed longitudinally. In most patients the levels of IFN-induced gene expression remained relatively stable over 3–12 months despite marked changes in disease activity. Nevertheless, in patients with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity. Conclusion: The findings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity.

Work Disability in Systemic Lupus Erythematosus

OBJECTIVEnTo determine the prevalence, accrual over time, and risk factors of work disability in patients with systemic lupus erythematosus (SLE).nnnMETHODSnWe studied 432 patients from an inception cohort. Work disability was measured from a single self-report question. Data were prospectively collected and included sociodemographic information, clinical lupus features including activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update [SLEDAI-2K]), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and organ involvement, as well as health status (Short Form 36 [SF-36]), comorbidity, and medication use. Students t-test and Wilcoxons rank sum test were used to compare continuous variables and chi-square tests were used for dichotomous variables. Descriptive survival curves of time to work disability were presented. Bivariate and multivariate logistic regressions were used to describe the relationships between clinically relevant factors and work disability.nnnRESULTSnOf 432 patients, 88% were women and 73% were white. Within the first year of diagnosis, 47% of patients were employed, 7% had a disability, and 7% were on sick leave. Overall, work disability was found in 98 (23%) patients. Risk factors for work disability found in the multivariate regression analysis were younger age at diagnosis, less education, fibromyalgia, hypertension, higher first-visit SLEDAI-2K score, and lower first-visit SF-36 score.nnnCONCLUSIONnWork disability is frequent in patients with SLE, with a cumulative prevalence of 23%. Work disability was associated with a complex array of health factors, including comorbidity, physical and mental health limitations, and clinical features of lupus, that warrant increased attention in future research.

Persistent proteinuria and dyslipidemia increase the risk of progressive chronic kidney disease in lupus erythematosus

Advances in immunotherapy have improved survival of patients with systemic lupus erythematosus who now face an increasing burden of chronic diseases including that of the kidney. As systemic inflammation is also thought to contribute directly to the progression of chronic kidney disease (CKD), we assessed this risk in patients with lupus, with and without a diagnosis of nephritis, and also identified modifiable risk factors. Accordingly, we enrolled 631 patients (predominantly Caucasian), of whom 504 were diagnosed with lupus within the first year and followed them an average of 11 years. Despite the presence of a chronic inflammatory disease, the rate of decline in renal function of 238 patients without nephritis was similar to that described for non-lupus patient cohorts. Progressive loss of kidney function developed exclusively in patients with lupus nephritis who had persistent proteinuria and dyslipidemia, although only six required dialysis or transplantation. The mortality rate was 16% with half of the deaths attributable to sepsis or cancer. Thus, despite the presence of a systemic inflammatory disease, the risk of progressive CKD in this lupus cohort was relatively low in the absence of nephritis. Hence, as in idiopathic glomerular disease, persistent proteinuria and dyslipidemia (modifiable risks) are the major factors for CKD progression in lupus patients with renal involvement.

Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) patients are often treated with glucocorticoids, which place them at risk of bone loss. Objectives The objectives of this article are to determine: (1) the prevalence of low bone mineral density (BMD) and factors associated with low BMD and (2) the prevalence of symptomatic fragility fractures in inception patients of the Toronto Lupus Cohort (TLC). Methods Prospectively collected data from the TLC (1996–2015) of inception patients’ first BMD were analyzed. For pre-menopausal women/males <50 years, BMD ‘below expected range for age’ was defined by Z-scoreu2009≤u2009−2.0 SD. For post-menopausal women/males age 50 or older, osteoporosis was defined by T-scoreu2009≤u2009−2.5 SD and low bone mass by T-score between −1.0 and −2.5 SD. Patients’ BMDs were defined as abnormal if Z-scoreu2009≤u2009−2.0 or T-scoreu2009<u2009−1.0 SD, and the remainder as normal. Descriptive analysis and logistic regression were employed. Results Of 1807 patients, 286 are inception patients with BMD results (mean age 37.9u2009±u200913.7 years); 88.8% are female. The overall prevalence of abnormal BMD is 31.5%. In pre-menopausal women (nu2009=u2009173), the prevalence of BMD below expected range is 17.3%. In post-menopausal women (nu2009=u200981), the prevalence of osteoporosis and low BMD are 12.3% and 43.2%, respectively. Age and cumulative dose of glucocorticoids are statistically significantly associated with abnormal BMD in multivariate analysis. Of 769 inception patients from TLC, 11.1% experienced symptomatic fragility fractures (peripheral and vertebral) over the course of their disease. Conclusion The prevalence of low BMD is high in SLE patients, and is associated with older age and higher cumulative glucocorticoid dose.

Defining low disease activity in systemic lupus erythematosus

To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short‐term outcomes.

Does renin‐angiotensin system blockade protect lupus nephritis patients from atherosclerotic cardiovascular events? A case‐control study

Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used as an adjuvant treatment in lupus nephritis (LN) patients with proteinuria. The primary aim of this study was to discover whether ACE inhibitors/ARBs have an atheroprotective effect similar to other, at‐risk, populations.

Association of Autoantibodies to Heat-Shock Protein 60 With Arterial Vascular Events in Patients With Antiphospholipid Antibodies

OBJECTIVEnAnti-heat shock protein 60 autoantibodies (anti-Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti-Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of anti-Hsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events.nnnMETHODSnThe study population was derived from 3 ongoing cohort studies: 2 independent systemic lupus erythematosus (SLE) registries and 1 cohort comprising SLE patients and non-SLE patients. Data from a total of 402 participants were captured; 199 of these participants had had confirmed vascular events (arterial vascular events in 102, venous vascular events in 76, and both arterial and venous vascular events in 21). Anti-Hsp60 were detected by enzyme-linked immunoassay, and association with vascular events was assessed by regression analysis.nnnRESULTSnMultiple regression analysis revealed that arterial vascular events were associated with male sex, age, and hypertension. Analyses of the vascular events according to their origin showed an association of anti-Hsp60 with arterial vascular events (odds ratio 2.26 [95% confidence interval 1.13-4.52]), but not with venous vascular events. Anti-Hsp60 increased the risk of arterial vascular events (odds ratio 5.54 [95% confidence interval 1.89-16.25]) in antiphospholipid antibody (aPL)-positive, but not aPL-negative, individuals.nnnCONCLUSIONnWe demonstrate that anti-Hsp60 are associated with an increased risk of arterial vascular events, but not venous vascular events, in aPL-positive individuals. These data suggest that anti-Hsp60 may serve as a useful biomarker to distinguish risk of arterial and venous vascular events in patients with aPL.

Psoriasis in systemic lupus erythematosus: a single-center experience

The coexistence of psoriasis with systemic lupus erythematosus (SLE) has been reported in limited case series, raising hypotheses about shared pathogenetic mechanisms. Nevertheless, important differences regarding treatment do exist. The aim of the present study was to determine the prevalence and characteristics of psoriasis in a defined cohort of lupus patients. Patients with psoriasis were retrieved from the University of Toronto Lupus Clinic from its inception in 1970 up to 2015. Charts were hand-searched to collect information concerning demographic, clinical, and therapeutic variables. Patients were matched with non-psoriasis lupus patients to identify the impact of supervening psoriasis on lupus activity, damage accrual, and venous thromboembolic (VTEs) and cardiovascular events (CVEs). Psoriasis was diagnosed in 63 patients (49 females, 14 males) for a prevalence of 3.46% (63/1823). The male-to-female ratio was significantly higher in non-psoriasis patients (0.286 vs. 0.138, pxa0=xa00.017). Plaque psoriasis was the most prominent type (55/63, 87.3%) whereas three patients had pustular disease; one had psoriatic arthritis. Nine patients (14.3%) were administered systemic treatment with methotrexate (nxa0=xa05), azathioprine (nxa0=xa01), ustekinumab (nxa0=xa03), and etanercept (nxa0=xa01). Psoriasis was definitely deteriorated by hydroxychloroquine in one patient. There was no significant impact of psoriasis on disease activity, damage accrual, VTEs, and CVEs. The prevalence of psoriasis was twice as high as that of the general Canadian population in this lupus cohort. Plaque psoriasis was the most prominent subtype, and topical treatment was adequate in the majority of patients. Supervening psoriasis had no significant impact on lupus activity and damage accrual.

Osteonecrosis in SLE: prevalence, patterns, outcomes and predictors

Objective Osteonecrosis is a serious comorbidity in patients with systemic lupus erythematosus. The aims of this study were to describe the prevalence of symptomatic osteonecrosis, determine the pattern of joint involvement, identify the outcomes and investigate predictive factors in a large cohort of patients with systemic lupus erythematosus followed prospectively. Methods At the Toronto Lupus Clinic patients have been followed prospectively according to a standard protocol since 1970. Osteonecrosis is recorded if patients are symptomatic and is confirmed by imaging. The site of osteonecrosis is recorded and whether or not surgery was performed. For determination of prevalence, pattern and outcome of osteonecrosis a longitudinal cohort design was performed. For the predictive factors, only patients with incident osteonecrosis were included and were matched for gender, year of entry to clinic (within 5 years), year of birth (within 5 years) and disease duration (within 3 years) with systemic lupus erythematosus patients without osteonecrosis. Results Of 1729 patients with systemic lupus erythematosus registered in the database, 234 (13.5%) developed symptomatic osteonecrosis in 581 sites. Hips and knees were most commonly affected and 47% of the patients had multiple sites involved. More than half of the joints involved at first occurrence of osteonecrosis had surgery. Univariate analysis identified black race, damage, elevated cholesterol and glucocorticosteroids as predictive factors, but glucocorticosteroids remained as the primary predictor for the development of osteonecrosis on multivariable analysis. Conclusion Despite advancements in the assessment and treatment of systemic lupus erythematosus, symptomatic osteonecrosis continues to be a significant comorbidity. Strategies to minimize glucocorticosteroid use are necessary to prevent this serious complication.

Disease evolution in late-onset and early-onset systemic lupus erythematosus:

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18–40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosisu2009±u2009SD 58.05u2009±u20097.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosisu2009±u2009SD 27.80u2009±u20095.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.