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1.
  • Pettersson, S., et al. (författare)
  • A comparison of patients and physicians assessments of disease activity using the Swedish version of the Systemic Lupus Activity Questionnaire
  • 2017
  • Ingår i: Scandinavian Journal of Rheumatology. - : TAYLOR & FRANCIS LTD. - 0300-9742 .- 1502-7732. ; 46:6, s. 474-483
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: We compared patients assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (amp;lt;1year) versus long (1year) disease duration.Method: Patients filled out the SLAQ before physicians assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearmans. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests.Results: We included 203 patients (79% women), with a median age of 45years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians SLAM without laboratory items (SLAM-nolab) and patients assessments were: SLAQ total, =0.685, Symptom score, =0.651, Flares, =0.547, and Patients global, =0.600. Of the symptom items, fatigue (=0.640), seizures (=0.635), and headache (=0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (amp;lt;0.24). Patients and physicians assessments were notably more discordant for patients with short disease durations.Conclusion: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients and physicians assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.
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2.
  • Abelson, A. K., et al. (författare)
  • No evidence of association between genetic variants of the PDCD1 ligands and SLE
  • 2007
  • Ingår i: Genes and Immunity. - : Nature Publishing Group. - 1476-5470 .- 1466-4879. ; 8:1, s. 69-74
  • Tidskriftsartikel (refereegranskat)abstract
    • PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z = 2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N = 149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N = 90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
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3.
  • Hober, S., et al. (författare)
  • Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
  • 2021
  • Ingår i: Clinical & Translational Immunology. - : WILEY. - 2050-0068. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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5.
  • Leonard, Dag, et al. (författare)
  • Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis
  • 2018
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 77:7, s. 1063-1069
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). We investigated whether single nucleotide polymorphisms (SNPs) at autoimmunity risk loci were associated with CVD in SLE and RA.Methods Patients with SLE (n=1045) were genotyped using the 200K Immunochip SNP array (Illumina). The allele frequency was compared between patients with and without different manifestations of CVD. Results were replicated in a second SLE cohort (n=1043) and in an RA cohort (n=824). We analysed publicly available genetic data from general population, performed electrophoretic mobility shift assays and measured cytokine levels and occurrence of antiphospholipid antibodies (aPLs).Results We identified two new putative risk loci associated with increased risk for CVD in two SLE populations, which remained after adjustment for traditional CVD risk factors. An IL19 risk allele, rs17581834(T) was associated with stroke/myocardial infarction (MI) in SLE (OR 2.3 (1.5 to 3.4), P=8.5x10(-5)) and RA (OR 2.8 (1.4 to 5.6), P=3.8x10(-3)), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5x10(-7)), but not in population controls. The IL19 risk allele affected protein binding, and SLE patients with the risk allele had increased levels of plasma-IL10 (P=0.004) and aPL (P=0.01). An SRP54-AS1 risk allele, rs799454(G) was associated with stroke/transient ischaemic attack in SLE (OR 1.7 (1.3 to 2.2), P=2.5x10(-5)) but not in RA. The SRP54-AS1 risk allele is an expression quantitative trait locus for four genes.Conclusions The IL19 risk allele was associated with stroke/MI in SLE and RA, but not in the general population, indicating that shared immune pathways may be involved in the CVD pathogenesis in inflammatory rheumatic diseases.
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6.
  • Pettersson, Susanne, et al. (författare)
  • An exploration of patient-reported symptoms in systemic lupus erythematosus and the relationship to health-related quality of life
  • 2012
  • Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 41:5, s. 383-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics, and disease characteristics (duration, activity, organ damage). Methods: In a cross-sectional study, patients with SLE (n = 324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analysed for patient demographics, disease duration, and results from the following questionnaires: the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the Systemic Lupus Activity Measure (SLAM), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology (SLICC/ACR) damage index. Results: Twenty-three symptom categories were identified. Fatigue (51%), pain (50%), and musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting fatigue showed a statistically significant impact on both mental and physical components of HRQoL. Patients with no present symptoms (10%) had higher HRQoL (p < 0.001) and lower levels of depression (p < 0.001), anxiety (p < 0.01), and disease activity (SLAM) (p < 0.001). Conclusion: Fatigue, pain, or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue.
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7.
  • Pettersson, Susanne, et al. (författare)
  • Lifestyle habits and fatigue among people with systemic lupus erythematosus and matched population controls
  • 2015
  • Ingår i: Lupus. - : Sage Publications. - 0961-2033 .- 1477-0962. ; 24:9, s. 955-965
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The objective of this paper is to identify clusters of fatigue in patients with systemic lupus erythematosus (SLE) and matched controls, and to analyze these clusters with respect to lifestyle habits, health-related quality of life (HRQoL), anxiety and depression.METHODS: Patients with SLE (n = 305) and age- and gender-matched population controls (n = 311) were included. Three measurements of fatigue (Fatigue Severity Scale (FSS), Vitality (VT, from SF-36) and Multidimensional Assessment of Fatigue scale (MAF) and hierarchic cluster analysis were used to define clusters with different degrees of fatigue. Lifestyle habits were investigated through questionnaires. HRQoL was assessed with the SF-36 and anxiety/depression with the Hospital Anxiety and Depression Scale.RESULTS: Three clusters, denominated "High," "Intermediate" and "Low" fatigue clusters, were identified. The "High" contained 80% patients, and 20% controls (median; VT 25, FSS 5.8, MAF 37.4). These had the most symptoms of depression (51%) and anxiety (34%), lowest HRQoL (p < 0.001) and they exercised least frequently. The "Intermediate" (48% patients and 52% controls) (median; VT 55, FSS 4.1, MAF 23.5) had similarities with the "Low" regarding sleep/rest whereas social status and smoking were closer to the "High." The"Low" contained 22% patients and 78% controls (median; VT 80, FSS 2.3, MAF 10.9). They had the highest perceived HRQoL (p < 0.001), least symptoms of anxiety (10%), no depression, smoked least (13%) and reported the highest percentage (24%) of exercising ≥ 3 times/week.CONCLUSION: Fatigue is common, but not a general feature of SLE. It is associated with depression, anxiety, low HRQoL and less physical exercise. Patients with SLE and population controls with a healthy lifestyle reported lower levels of fatigue. Whether lifestyle changes can reduce fatigue, which is a major problem for a majority of SLE patients, needs to be further explored.
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8.
  • Pettersson, Susanne, et al. (författare)
  • Women's experience of SLE-related fatigue : a focus group interview study
  • 2010
  • Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 49:10, s. 1935-1942
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to describe women's experience of SLE-related fatigue, how they express the feeling of fatigue, impact on life and strategies developed to manage fatigue in daily living.METHOD: Seven, semi-structured focus group discussions with 33 women were audio-taped, transcribed verbatim and analysed according to qualitative content analysis.RESULTS: Perceptions of SLE-related fatigue were sorted into four themes. Nature of Fatigue, involved the sensation, occurrence and character. Aspects Affected by Fatigue described emotions that arose together with fatigue as well as aspects of work, family life, social contacts and leisure activities that were affected by fatigue. Striving Towards Power and Control concluded the array of ways used to manage daily life and were categorized into the mental struggle, structure, restrict and provide. Factors Influencing the Perception of Fatigue described understanding from their surroundings and pain as strongly influencing the experience and perception of fatigue.CONCLUSION: SLE-related fatigue was portrayed as an overwhelming phenomenon with an unpredictable character, resulting in the feeling that fatigue dominates and controls most situations in life. The choice of strategies was described as a balance with implications for how fatigue limited a person's life. Health care professionals are advised to take a more active role to empower people with SLE to find their own balance as a way to achieve a feeling of being in control.
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9.
  • Svenungsson, E., et al. (författare)
  • Quick Systemic Lupus Activity Questionnaire (Q-SLAQ): a simplified version of SLAQ for patient-reported disease activity
  • 2021
  • Ingår i: Lupus Science & Medicine. - : BMJ Publishing Group Ltd. - 2053-8790 .- 1625-9823. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Most indices of disease activity in SLE combine physicians' assessments and laboratory tests. However, there is also a need to capture patients' perspectives of disease activity. Consequently, we need new, preferably quick and easy instruments to collect this information, which can be very useful for online consultations and registry purposes. We compared patients' assessments of SLE disease impact/activity, as reported by a shorter version of the Quick Systemic Lupus Activity Questionnaire (Q-SLAQ), with physicians' assessments using SLE Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI-2K) and with the original Systemic Lupus Activity Questionnaire (SLAQ). Methods Patients with SLE (n=115), with a disease duration of 15 years (IQR 17), completed the Q-SLAQ prior to physicians' assessments by SLAM and SLEDAI-2K. A second set of patients (n=85) with similar characteristics filled out Q-SLAQ and SLAQ. Spearman's rho correlations were explored between patients' total Q-SLAQ and subscales (Symptom Score, Patient's Global Disease Activity) and physicians' SLAM and SLEDAI-2K, with and without laboratory items (SLAM-nolab and SLEDAI-2K-nolab) and SLAQ. Corresponding items in Q-SLAQ and SLAM were compared. Results Correlations between patients' and physicians' assessments were higher for SLAM-nolab (total Q-SLAQ, rho=0.71; Symptom Score, rho=0.67; and Patient's Global Disease Activity, rho=0.68) than for the original SLAM (total Q-SLAQ, rho=0.53; Symptom Score, rho=0.50; and Patient's Global Disease Activity, rho=0.53). Regarding specific symptoms, fatigue (rho=0.72) and alopecia (rho=0.71) correlated best, while pulmonary/respiratory symptoms correlated least (rho=0.19, p=0.039). Physicians assessment with SLEDAI-2K-nolab correlated weakly with patients' assessments (total Q-SLAQ, rho=0.30; Symptom Score, rho=0.30; and Patient's Global Disease Activity, rho=0.36). Bivariate correlations between Q-SLAQ and SLAQ were good (rho=0.82-0.96). Conclusions Q-SLAQ and the original SLAQ performed equally well, demonstrating that the shorter Q-SLAQ can safely be used to monitor patients' perception of disease impact/activity. We also noted an intriguing discrepancy between physicians' and patients' evaluations of pulmonary/respiratory symptoms, which requires further investigations.
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10.
  • Wang, C., et al. (författare)
  • Contribution of IKBKE and IFIH1 gene variants to SLE susceptibility
  • 2013
  • Ingår i: Genes and Immunity. - : Nature Publishing Group. - 1476-5470 .- 1466-4879. ; 14:4, s. 217-222
  • Tidskriftsartikel (refereegranskat)abstract
    • The type I interferon system genes IKBKE and IFIH1 are associated with the risk of systemic lupus erythematosus (SLE). To identify the sequence variants that are able to account for the disease association, we resequenced the genes IKBKE and IFIH1. Eighty-six single-nucleotide variants (SNVs) with potentially functional effect or differences in allele frequencies between patients and controls determined by sequencing were further genotyped in 1140 SLE patients and 2060 controls. In addition, 108 imputed sequence variants in IKBKE and IFIH1 were included in the association analysis. Ten IKBKE SNVs and three IFIH1 SNVs were associated with SLE. The SNVs rs1539241 and rs12142086 tagged two independent association signals in IKBKE, and the haplotype carrying their risk alleles showed an odds ratio of 1.68 (P-value = 1.0 x 10(-5)). The risk allele of rs12142086 affects the binding of splicing factor 1 in vitro and could thus influence its transcriptional regulatory function. Two independent association signals were also detected in IFIH1, which were tagged by a low-frequency SNV rs78456138 and a missense SNV rs3747517. Their joint effect is protective against SLE (odds ratio = 0.56; P-value = 6.6 x 10(-3)). In conclusion, we have identified new SLE-associated sequence variants in IKBKE and IFIH1, and proposed functional hypotheses for the association signals.
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