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.
Smoking can induce autoantibodies in persons who are genetically predisposed to rheumatoid arthritis. We investigated the association between smoking and antiphospholipid antibodies (aPL) in systemic ...lupus erythematosus (SLE), a question not previously addressed. Further, we explored the relationship between smoking, aPL and vascular events (arterial and venous, VE).
In this cross-sectional study, clinical evaluation and questionnaire data were collected from 367 prevalent SLE patients. At the same time, we measured aPL (anticardiolipin (aCL), anti-β2 glycoprotein-1 (aβ2GP1) antibodies IgG/IgM/IgA, and lupus anticoagulant (LA)), and a large set of other SLE-associated autoantibodies for comparison. Association analyses using logistic regression models with smoking, (ever, former and current with never as reference) and antibody status as outcome variable were performed. As a secondary outcome, we investigated the associations between aPL, smoking and VE.
In multivariable-adjusted models ever, and in particular former, cigarette smoking was associated with the most pathogenic aPL; LA, aCL IgG and aβ2GP1 IgG. Other SLE-associated autoantibodies were not associated with smoking. The combination of smoking and aPL was strongly associated with VE. We noted a positive interaction between smoking-LA and smoking-'triple aPL' positivity for previous VE.
We investigated a large set of commonly occurring autoantibodies in SLE, but only aPL were positively associated with a history of smoking. This association was especially apparent in former smokers. Among ever regular smokers who were aPL positive, we observed a strikingly high frequency of former VE. The underlying mechanisms and temporality between smoking, aPL and VE need further investigations.
Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical ...atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.
A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.
Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.
In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.
Objective
Accumulating evidence supports an impaired health‐related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of 2 biologic treatments ...on HRQoL of patients with SLE.
Methods
Patients with SLE from the Karolinska University Hospital treated with belimumab (n = 34) or rituximab (n = 35) were included; normative values derived from Swedish population‐based controls matched for age and sex were used for the purpose of comparisons. Data were collected prospectively at treatment initiation and at months 3, 6, 12, and 24, using the Short Form 36 (SF‐36) health questionnaire, the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue) scale, the EuroQol 5‐dimension (EQ‐5D) instrument, and the Stanford Health Assessment Questionnaire disability index (HAQ DI).
Results
Substantial decrements from Swedish norms were observed across all SF‐36 domains at baseline. Patients treated with belimumab reported gradual improvements in the SF‐36 physical component summary (significant from month 12; P = 0.023) and FACIT‐Fatigue (significant by month 24; P = 0.001), no changes in EQ‐5D scores, and improvements in HAQ DI by month 6 (P = 0.014). Patients treated with rituximab showed rapid improvements in the SF‐36 mental component summary and FACIT‐Fatigue by month 3 (P = 0.031 and P = 0.007, respectively), as well as improvements in EQ‐5D at month 6 (P = 0.016) and HAQ DI at month 3 (P = 0.033). Based on baseline evaluations, patients receiving antimalarial agents (n = 33) performed better in the SF‐36 social functioning (P = 0.022) and mental health (P = 0.023) domains compared to patients who did not receive antimalarial agents (n = 36).
Conclusion
Our results corroborated previous findings of considerable HRQoL impairments in patients with SLE. Patients' perceptions of HRQoL showed discrepant patterns over time in the 2 treatment groups and could provide additional information along with the clinical evaluation of biologic therapy in SLE. Further survey on the effects of antimalarial agents on the HRQoL of patients with SLE in larger cohorts is merited.
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 (< 1 year) versus long (≥ 1 year) 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 Spearman's ρ. 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 45 years 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, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 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.
ObjectiveAccumulating evidence supports an impaired health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of 2 biologic treatments on ...HRQoL of patients with SLE. MethodsPatients with SLE from the Karolinska University Hospital treated with belimumab (n = 34) or rituximab (n = 35) were included; normative values derived from Swedish population-based controls matched for age and sex were used for the purpose of comparisons. Data were collected prospectively at treatment initiation and at months 3, 6, 12, and 24, using the Short Form 36 (SF-36) health questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, the EuroQol 5-dimension (EQ-5D) instrument, and the Stanford Health Assessment Questionnaire disability index (HAQ DI). ResultsSubstantial decrements from Swedish norms were observed across all SF-36 domains at baseline. Patients treated with belimumab reported gradual improvements in the SF-36 physical component summary (significant from month 12; P = 0.023) and FACIT-Fatigue (significant by month 24; P = 0.001), no changes in EQ-5D scores, and improvements in HAQ DI by month 6 (P = 0.014). Patients treated with rituximab showed rapid improvements in the SF-36 mental component summary and FACIT-Fatigue by month 3 (P = 0.031 and P = 0.007, respectively), as well as improvements in EQ-5D at month 6 (P = 0.016) and HAQ DI at month 3 (P = 0.033). Based on baseline evaluations, patients receiving antimalarial agents (n = 33) performed better in the SF-36 social functioning (P = 0.022) and mental health (P = 0.023) domains compared to patients who did not receive antimalarial agents (n = 36). ConclusionOur results corroborated previous findings of considerable HRQoL impairments in patients with SLE. Patients perceptions of HRQoL showed discrepant patterns over time in the 2 treatment groups and could provide additional information along with the clinical evaluation of biologic therapy in SLE. Further survey on the effects of antimalarial agents on the HRQoL of patients with SLE in larger cohorts is merited.
Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical ...research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.
The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of ...type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi–Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.
In this paper we review on the technologies available to make globally quantitative observations of particles, in general, and plankton, in particular, in the world oceans, and for sizes varying from ...sub-micron to centimeters. Some of these technologies have been available for years while others have only recently emerged. Use of these technologies is critical to improve understanding of the processes that control abundances, distributions and composition of plankton, provide data necessary to constrain and improve ecosystem and biogeochemical models, and forecast changes in marine ecosystems in light of climate change. In this paper we begin by providing the motivation for plankton observations, quantification and diversity qualification on a global scale. We then expand on the state-of-the-art, detailing a variety of relevant and (mostly) mature technologies and measurements, including bulk measurements of plankton, pigment composition, uses of genomic, optical, acoustical methods and analysis using particles counters, flow cytometers and quantitative imaging devices. We follow by highlighting the requirements necessary for a plankton observing system, the approach to achieve it and associated challenges. We conclude with ranked action-item recommendations for the next ten years to move towards our vision of a holistic ocean-wide plankton observing system. Particularly, we suggest to begin with a demonstration project on a GO-SHIP line and/or a long-term observation site and expand from there ensuring that issues associated with methods, observation tools, data analysis, quality assessment and curation are addressed early in the implementation. Global coordination is key for the success of this vision and will bring new insights on processes associated with nutrient regeneration, ocean production, fisheries, and carbon sequestration.
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