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1.
  • Ajeganova, S, et al. (författare)
  • Patients with SLE have higher risk of cardiovascular events and mortality in comparison with controls with the same levels of traditional risk factors and intima-media measures, which is related to accumulated disease damage and antiphospholipid syndrome: a case-control study over 10 years
  • 2021
  • Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • SLE is a strong risk factor for premature cardiovascular (CV) disease and mortality. We investigated which factors could explain poor prognosis in SLE compared with controls.MethodsPatients with SLE and population controls without history of clinical CV events who performed carotid ultrasound examination were recruited for this study. The outcome was incident CV event and death. Event-free survival rates were compared using Kaplan-Meier curves. Relative HR (95% CI) was used to estimate risk of outcome.ResultsPatients (n=99, 87% female), aged 47 (13) years and with a disease duration of 12 (9) years, had mild disease at inclusion, Systemic Lupus Erythematosus Diseases Activity Index score of 3 (1–6) and Systemic Lupus International Collaborating Clinics (SLICC) Damage Index score of 0 (0–1). The controls (n=109, 91% female) were 49 (12) years old. Baseline carotid intima-media thickness (cIMT) did not differ between the groups, but plaques were more prevalent in patients (p=0.068). During 10.1 (9.8-10.2) years, 12 patients and 4 controls reached the outcome (p=0.022). Compared with the controls, the risk of the adverse outcome in patients increased threefold to fourfold taking into account age, gender, history of smoking and diabetes, family history of CV, baseline body mass index, waist circumference, C reactive protein, total cholesterol, high-density lipoprotein, low-density lipoprotein, dyslipidaemia, cIMT and presence of carotid plaque. In patients, higher SLICC score and SLE-antiphospholipid syndrome (SLE-APS) were associated with increased risk of the adverse outcome, with respective HRs of 1.66 (95% CI 1.20 to 2.28) and 9.08 (95% CI 2.71 to 30.5), as was cIMT with an HR of 1.006 (95% CI 1.002 to 1.01). The combination of SLICC and SLE-APS with cIMT significantly improved prediction of the adverse outcome (p<0.001).ConclusionIn patients with mild SLE of more than 10 years duration, there is a threefold to fourfold increased risk of CV events and death compared with persons who do not have SLE with similar pattern of traditional CV risk factors, cIMT and presence of carotid plaque. SLICC, SLE-APS and subclinical atherosclerosis may indicate a group at risk of worse outcome in SLE.
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2.
  • Ajeganova, S, et al. (författare)
  • Similar progression of carotid intima-media thickness in 7-year surveillance of patients with mild SLE and controls, but this progression is still promoted by dyslipidaemia, lower HDL levels, hypertension, history of lupus nephritis and a higher prednisolone usage in patients
  • 2020
  • Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 7:1, s. e000362-
  • Tidskriftsartikel (refereegranskat)abstract
    • To compare progression of subclinical atherosclerosis and factors promoting it in patients with SLE and controls.MethodsConsecutive patients with SLE and age-matched, sex-matched population controls from the SLEVIC cohort were assessed at inclusion and after 7 years with standardised data collection and carotid ultrasound. Effect of risk factors on carotid intima–media thickness (cIMT) progression was examined with adjusted linear mixed models.ResultsA total of 77 patients and 74 controls, 68% and 61% of the original cohort, completed follow-up. The patients were (mean) 47 years old, 90% were women, and controls were 51 years old, 92% women. Patients had disease duration of (mean) 11 years, mild disease activity and low severity at both assessments. Baseline cIMT did not differ between the groups. An average absolute cIMT progression was 0.009 mm/year in patients and 0.011 mm/year in controls, intergroup difference p=0.9.Of factors at inclusion, dyslipidaemia, lower levels of high-density lipoprotein (HDL) and carotid plaque in patients and controls, and higher systolic blood pressure, total cholesterol:HDL and LDL:HDL ratios and triglycerides in patients were associated with cIMT progression. Of factors at follow-up, hypertension and blood lipids in patients and HDL in controls were significantly associated with cIMT progression. History of lupus nephritis and a higher average dose of prednisolone used since diagnosis were associated with cIMT progression in patients. Associations of risk factors with cIMT progression were stronger in presence of plaques.ConclusionWe observed a statistically comparable progression of cIMT in patients with mild SLE and controls over 7 years, which implies that progression of subclinical atherosclerosis in some patients with SLE could follow that of the general population. Traditional cardiovascular (CV) risk factors, history of lupus nephritis and higher use of corticosteroids promote cIMT progression in SLE. Detection of carotid plaque may add to CV risk stratification.
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3.
  • Almeida-Brasil, Celline C., et al. (författare)
  • Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine
  • 2022
  • Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. Results We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). Conclusions This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.
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4.
  • Andraos, Rama, et al. (författare)
  • Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
  • 2022
  • Ingår i: Lupus Science and Medicine. - : BMJ PUBLISHING GROUP. - 2053-8790. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveSLE, primary Sjogrens syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-alpha, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-alpha was quantified by ELISA. Self-reported data on Raynauds phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-alpha levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.
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5.
  • Antovic, A, et al. (författare)
  • Obstetric antiphospholipid syndrome
  • 2018
  • Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 5:1, s. e000197-
  • Tidskriftsartikel (refereegranskat)abstract
    • The present clinical and laboratory classification criteria for antiphospholipid syndrome (APS) were established in Sydney, Australia, in 2006. In this review, we focus on the obstetric subset of APS (OAPS), defined by persistent positivity for antiphospholipid antibodies together with either early recurrent pregnancy loss, early fetal death, stillbirth or premature birth <34 gestational weeks due to pre-eclampsia, eclampsia and placental insufficiency. It is important to diagnose these cases since most women suffering from OAPS can, when given appropriate treatment, have successful pregnancies. Furthermore, patients with OAPS may, depending on the antibody profile, be at enhanced risk of thrombotic events later in life. We present an update on the present knowledge of possible underlying pathogenesis, risk factors and risk estimations for adverse pregnancy outcomes before and during pregnancy, current treatment concepts, and long-term outcomes for women with OAPS and their children.
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6.
  • Arat, Seher, et al. (författare)
  • Illness representations of systemic lupus erythematosus and systemic sclerosis: a comparison of patients, their rheumatologists and their general practitioners.
  • 2017
  • Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Discrepancies in illness representations between patients and physicians result in treatment difficulties, decreased well-being of patients and misunderstandings and disrupted communication. Hence, the objective of this study was to compare illness perceptions of individual patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), their rheumatologists and their general practitioners (GPs) and explore potential differences.This study has a cross-sectional design. Patients with SLE and SSc, who were followed at the rheumatology department of the University Hospitals Leuven (Belgium), completed the revised Illness Perception Questionnaire which measures patients' perceptions of their condition and captures nine dimensions. Physicians completed the Revised Illness Perception Questionnaire for Healthcare Professionals which consists of seven dimensions and measures perceptions of the healthcare professional regarding the disease of their patients. Intraclass correlation was performed to examine relationships between pairs of respondents; Cohen's d was used for estimating the magnitude of the difference.Questionnaires were sent to 284 patients of whom 241 (113 SSc and 128 SLE patients) were included. Five rheumatologists and 160 GPs participated. For both diseases, positive correlations were found for 'consequences', 'illness coherence' and 'emotional representations' among patients, rheumatologists and GPs. GPs scored higher on the 'consequences' of these diseases for the patient (d=0.71 for SLE; d=0.80 for SSc). Differences between rheumatologists and GPs were small for SSc and moderate to large for 'consequences' (d=0.56) and 'timeline acute/chronic' (d=0.95) in SLE with higher scores for GPs.For both diseases and among the three groups, significant correlations are detected for the dimensions 'consequences', 'illness coherence' and 'emotional representations'. Differences between rheumatologists and GPs were mainly detected in the case of SLE patients. This can have implications for the collaboration between these two groups of physicians in daily clinical practice.NCT02655640; Pre-results.
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7.
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8.
  • Bernatsky, Sasha, et al. (författare)
  • Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
  • 2017
  • Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 4:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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9.
  • Buyon, J, et al. (författare)
  • Editorial
  • 2014
  • Ingår i: Lupus science & medicine. - : BMJ. - 2053-8790. ; 1:1, s. e000028-
  • Tidskriftsartikel (refereegranskat)
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10.
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