| 1. |
- Bengtsson, Johan, et al.
(författare)
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A Robot Playing Scrabble Using Visual Feedback
- 2000
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Ingår i: IFAC Proceedings Volumes. ; 33:27, s. 551-556
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Tidskriftsartikel (refereegranskat)abstract
- Today most industrial robot systems use dedicated and rather limited sensors, and available control systems provide limited support for feedback control. Aiming towards more autonomous robot systems, we want to improve flexibility. The game Scrabble is used as a test problem capturing these aspects. Our approach is to incorporate visual servoing and a conventional powerful off-line prograrnrning (OLP) system into the real-time control system, providing task specification and visual debugging. We use the OLP tool Envision from Deneb and an ABB robot with reconfigured control system, where the control system has an Open Robot Control architecture (ORC). The vision system is connected to a host computer and the camera is attached to the robot gripper. By extending the control system, we have designed and implemented both the vision system and the application for the Scrabble game. Our system implementation shows that ORC constitutes a necessary support for incorporation of real-time visual feedback and that OLP may effectively be used with real-time feedback of sensor data.
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| 2. |
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| 3. |
- Sandling, Johanna K., et al.
(författare)
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A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:4, s. 479-484
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Tidskriftsartikel (refereegranskat)abstract
- Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.
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| 4. |
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| 5. |
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| 6. |
- Appelgren, Daniel, et al.
(författare)
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Active NET formation in Libman–Sacks endocarditis without antiphospholipid antibodies : A dramatic onset of systemic lupus erythematosus
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:6, s. 310-318
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Tidskriftsartikel (refereegranskat)abstract
- Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman–Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman–Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p =.0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r = 0.65, p =.16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman–Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.
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| 7. |
- Bengtsson, Anders, 1954, et al.
(författare)
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Effects on complement activation of a new continuous autotransfusion system.
- 1997
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Ingår i: Transfusion medicine (Oxford, England). - 0958-7578. ; 7:2, s. 107-13
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic blood transfusions may subject patients to risks of infection and allergic reactions. Various techniques for transfusion of shed blood have been developed. The aim of this study was to evaluate a new continuous autotransfusion system (Fresenius CATS) as regards its impact on the complement system, and on erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin, leucocytes, platelets, albumin and protein were determined in the patient's blood preoperatively, 1 min before the start of transfusion, 15 and 60 min after transfusion; and in the reservoir, in the waste bag and in the retransfusion blood. Increased concentrations of C3a and SC5b-9 were found in the collected reservoir blood (P < 0.05). The washing and centrifugation procedure reduced these concentrations (< 0.001). High levels of free haemoglobin were found in the collected blood as well as in the processed product. The median haemoglobin level in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators from the complement cascade are removed by continuous autotransfusion technique. The processed blood contains high levels of free haemoglobin.
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| 8. |
- Bengtsson, Anders K.H., et al.
(författare)
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Particles, superparticles and twistors
- 1987
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Ingår i: Phys. Rev. D36 (1987) 1766.
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Tidskriftsartikel (refereegranskat)abstract
- The covariant Green-Schwarz action for a superstring has never been quantized covariantly. The physics behind this is discussed. We then consider the corresponding point-particle action in four dimensions, and write down a master action from which it can be obtained as a gauge choice: the ‘‘space-time gauge.’’ There is also a ‘‘twistor gauge,’’ in which covariant quantization is straightforward (as noted previously by Shirafuji).
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| 9. |
- Bengtsson, Anders, et al.
(författare)
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Microarray image analysis: background estimation using quantile and morphological filters
- 2006
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a microarray experiment the difference in expression between genes on the same slide is up to 103 fold or more. At low expression, even a small error in the estimate will have great influence on the final test and reference ratios. In addition to the true spot intensity the scanned signal consists of different kinds of noise referred to as background. In order to assess the true spot intensity background must be subtracted. The standard approach to estimate background intensities is to assume they are equal to the intensity levels between spots. In the literature, morphological opening is suggested to be one of the best methods for estimating background this way. Results: This paper examines fundamental properties of rank and quantile filters, which include morphological filters at the extremes, with focus on their ability to estimate between-spot intensity levels. The bias and variance of these filter estimates are driven by the number of background pixels used and their distributions. A new rank-filter algorithm is implemented and compared to methods available in Spot by CSIRO and GenePix Pro by Axon Instruments. Spot's morphological opening has a mean bias between -47 and -248 compared to a bias between 2 and -2 for the rank filter and the variability of the morphological opening estimate is 3 times higher than for the rank filter. The mean bias of Spot's second method, morph. close. open, is between -5 and -16 and the variability is approximately the same as for morphological opening. The variability of GenePix Pro's region-based estimate is more than ten times higher than the variability of the rank-filter estimate and with slightly more bias. The large variability is because the size of the background window changes with spot size. To overcome this, a non-adaptive region-based method is implemented. Its bias and variability are comparable to that of the rank filter. Conclusion: The performance of more advanced rank filters is equal to the best region-based methods. However, in order to get unbiased estimates these filters have to be implemented with great care. The performance of morphological opening is in general poor with a substantial spatial-dependent bias.
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| 10. |
- Bengtsson, Anders, et al.
(författare)
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No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19
- 2000
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 59:1, s. 64-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual seroprevalence in epidemiologically defined SLE populations has previously been reported. METHODS: Sera from 99 SLE patients from a defined area in Southern Sweden, representing 88% of all new SLE cases 1981-1995 within the Lund-Orup Health Care district with 175 000 adult inhabitants (> 15 years of age), and sera from 99 age and sex matched healthy controls were investigated for the presence of IgG parvovirus antibodies. Two different commercially available EIA kits were used; one using E coli synthesised parvovirus VP1/VP2 antigen, and one using baculovirus derived parvovirus VP2 antigen. RESULTS: The EIA using baculovirus derived antigen was more sensitive and surprisingly the controls were more often positive than the SLE patients were (79% versus 65%, chi(2) p=0.027). No difference between the groups was seen with the EIA using E coli derived antigen (46% versus 49%). Titration experiments indicated that the discordance between the two tests was a matter of sensitivity rather than specificity. CONCLUSION: No evidence was found of human parvovirus B19 infection being more prevalent among SLE patients. On the contrary, in one of the parvovirus EIAs the controls were more often positive than the SLE patients were.
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| 11. |
- Bengtsson, Christine, et al.
(författare)
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Systemic lupus erythematosus and cardiac risk factors : medical record documentation and patient adherence
- 2011
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Ingår i: Lupus. - Houndmills, Basingstoke, Hampshire : Stockton. - 0961-2033 .- 1477-0962. ; 20:10, s. 1057-1062
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Tidskriftsartikel (refereegranskat)abstract
- This study explores patients' knowledge of cardiac risk factors (CRFs), analyses how information and advice about CRFs are documented in clinical practice, and assesses patient adherence to received instructions to decrease CRFs. Systemic lupus erythematosus (SLE) patients with >= 4 ACR criteria participated through completing a validated cardiovascular health questionnaire (CHQ). Kappa statistics were used to compare medical records with the self-reported CHQ (agreement) and to evaluate adherence. Two hundred and eleven (72%) of the known patients with SLE participated. The mean age of the patients was 55 years. More than 70% of the SLE patients considered hypertension, obesity, smoking and hypercholesterolaemia to be very important CRFs. The agreement between medical record documentation and patients' reports was moderate for hypertension, overweight and hypercholesterolaemia (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). Patients' self-reported adherence to advice they had received regarding medication was substantial to perfect (kappa 0.65-1.0). For lifestyle changes in patients with hypertension and overweight, adherence was only fair to moderate (kappa 0.13-0.47). Swedish SLE patients' awareness of traditional CRFs was good in this study. However, the agreement between patients' self-reports and medical record documentation of CRF profiles, and patients' adherence to medical advice to CRF profiles, could be improved. Lupus (2011) 20, 1057-1062.
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| 12. |
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| 13. |
- Bernander, Stig, et al.
(författare)
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Downhill progressive landslides in long natural slopes: triggering agents and landslide phases modeled with a finite difference method
- 2016
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Ingår i: Canadian geotechnical journal (Print). - : Canadian Science Publishing. - 0008-3674 .- 1208-6010. ; 53:10, s. 1565-1582
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Tidskriftsartikel (refereegranskat)abstract
- A large landslide in Tuve (Gothenburg, Sweden 1977) initiated the development of a model for slope stability analysis taking the deformation-softening of soft sensitive clays into consideration. The model studies triggering agents and five phases in progressive slope failure are identified: (1) in-situ, (2) disturbance, (3) unstable ‘dynamic’, (4) transitory (or permanent) equilibrium, and (5) ‘global’ failure. The clay resistance in these phases may differ widely; mostly due to different rates of loading. Two time dependent failure criteria are defined: (i) the triggering load condition in the disturbance Phase (2), and (ii) the transitory equilibrium in Phase (4), indicating whether minor downhill displacements or a veritable landslide catastrophe will occur. The analysis explains why downhill landslides tend to spread over vast areas of almost horizontal ground further down-slope. The model has been applied to landslides in Scandinavia and Canada. Three case studies are briefly discussed. The model is a finite difference approach, where local downhill deformations caused by normal forces is maintained compatible with deviatory shear deformations above the potential (or the established) failure surface. Software and an easy-to-use spreadsheet are introduced as well as recent developments. See also Video Abstract.
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| 14. |
- Carlsson, Anders, et al.
(författare)
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Serum protein profiling of systemic lupus erythematosus and systemic sclerosis using recombinant antibody microarrays.
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are two severe autoimmune connective tissue diseases. The fundamental knowledge about their aetiology is limited and the conditions display complex pathogenesis, multifaceted presentations, and unpredictable courses. Despite significant efforts, the lack of fully validated biomarkers enabling diagnosis, classification, and monitoring of disease activity represents significant unmet clinical needs. In this discovery study, we have for the first time used recombinant antibody microarrays for miniaturized, multiplexed serum protein profiling of SLE and SSc, targeting mainly immunoregulatory proteins. The data showed that several candidate SLE-associated multiplexed serum biomarker signatures were delineated, reflecting disease (diagnosis), disease severity (phenotypic subsets) and disease activity. Selected differentially expressed markers were validated using orthogonal assays and a second, independent patient cohort. Further, biomarker signatures differentiating SLE versus SSc were demonstrated, and the observed differences increased with severity of SLE. In contrast, the data showed that the serum profiles of SSc versus healthy controls were more similar. Hence, we have shown that affinity proteomics could be used to de-convolute crude, non-fractionated serum proteomes, extracting molecular portraits of SLE and SSc, further enhancing our fundamental understanding of these complex autoimmune conditions.
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| 15. |
- Carlsson Almlöf, Jonas, et al.
(författare)
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Novel risk genes for systemic lupus erythematosus predicted by random forest classification
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.
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| 16. |
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| 17. |
- Funkquist, Anders, 1977-, et al.
(författare)
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Low CSF/serum ratio of free T4 is associated with decreased quality of life in mild hypothyroidism – A pilot study : CSF/s-T4 associated with QoL in hypothyroidism
- 2020
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Ingår i: Journal of Clinical and Translational Endocrinology. - Netherlands : Elsevier BV. - 2214-6237. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background & Objective: Patients with mild hypothyroidism often are depressed and have impaired quality of life despite serum free-T4 and T3 within reference values. Therefore, we investigated whether their symptoms were dependent on the concentrations of free -T4 and T3 in the circulation and cerebrospinal fluid (CSF). Methods: Twenty-five newly diagnosed, untreated hypothyroid subjects and as many age- and sex-matched healthy controls were investigated. Blood and CSF sampling was performed in the morning after an overnight fast. Quality of life (QoL) was assessed by a Likert scale. In the hypothyroid subjects, the MADRS rating scale was also used to evaluate symptoms of depression. Furthermore, the results obtained by the questionnaires were related to serum and CSF levels of free- T4 and T3 as well as the ratios between them in CSF and in serum. Results: Self-reported health was considerably lower in hypothyroid subjects. MADRS was considerably higher than the normal range for healthy individuals. Low CSF/serum free-T4 ratio was correlated with an increased depressed state according to MADRS (p < 0.01), and in addition, CSF/serum free-T4 ratio correlated positively with the self-reported general health Likert scale (p < 0.05). Concentrations of TSH, or free-T3 in serum or CSF, were not associated with an increased depressed state or self-reported general health. Conclusions: Low CSF/serum ratio of free-T4 was correlated with impaired general health and mood, in contrast to serum measurements not showing any correlations. These findings might partly explain why some patients with hypothyroidism suffer from mental symptoms, despite adequate serum levels of free-T4. However, the findings need to be confirmed in further and larger studies.
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| 18. |
- Gäbel, Jakob, 1971, et al.
(författare)
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Cell salvage of cardiotomy suction blood improves the balance between pro- and anti-inflammatory cytokines after cardiac surgery.
- 2013
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 44:3, s. 506-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The inflammatory response after cardiac surgery is characterized by a profound release of pro- and anti-inflammatory cytokines. Recent data suggest that the balance between pro- and anti-inflammatory cytokines is of greater importance than the absolute levels. Retransfusion of unwashed cardiotomy suction blood contributes to the inflammatory response, but the balance between pro- and anti-inflammatory cytokines in cardiotomy suction blood and whether cell salvage before retransfusion influences the systemic balance have not been investigated previously. METHODS: Twenty-five coronary artery bypass grafting patients were randomized to either cell salvage of cardiotomy suction blood or no cell salvage before retransfusion. Plasma levels of three anti-inflammatory cytokines [interleukin (IL)-1 receptor antagonist, IL-4 and IL-10] and two proinflammatory cytokines (tumour necrosis factor-alpha and IL-6), and the IL-6-to-IL-10 ratio was measured in cardiotomy suction blood before and after cell salvage, and in the systemic circulation before, during and after surgery. RESULTS: Plasma levels of all cytokines except IL-4 and IL-10 were significantly higher in cardiotomy suction blood than in the systemic circulation. The IL-6-to-IL-10 ratio was 6-fold higher in cardiotomy suction blood than in the systemic circulation [median 10.2 (range 1.1-75) vs 1.7 (0.2-24), P < 0.001]. Cell salvage reduced plasma levels of cytokines in cardiotomy suction blood and improved the systemic IL-6-to-IL-10 ratio 24 h after surgery [median 5.2 (3.6-17) vs 12.4 (4.9-31)] compared with no cell salvage (P = 0.032). CONCLUSIONS: The balance of pro- and anti-inflammatory cytokines in cardiotomy suction blood is unfavourable. Cell salvage reduces the absolute levels of both pro- and anti-inflammatory cytokines in cardiotomy suction blood and improves the balance in the systemic circulation after surgery.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Hu, Min, 1979-, et al.
(författare)
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Grading of sawn timber using the vibration technique : locating imperfections based on flexural mode shapes
- 2011
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Ingår i: 17th international nondestructive testing and evaluation of wood symposium. - Sopron, Hungary : University of West Hungary. - 9789639883819 ; , s. 269-276
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Konferensbidrag (refereegranskat)abstract
- The present study aims at investigating the potential of using mode shape or mode shape curvature (MSC) for detecting defects in wooden beams. It includes modal analysis, Finite Element (FE) modeling and visual scanning. An FE model was created to investigate the effect of defects of different size and location on the mode shape/MSC. The mode shape/MSC showed a good potential to be used for finding defects. An experimental study on 17 boards of Norway spruce, dimensions of 50×150×3900 mm, was conducted using experimental modal analysis. The findings reveal that: (1) the mode shape/MSC studied in the FE-model could be used to locate defects, (2) the method is very sensitive to measurement noise and it requires an accurately measured mode shape, (3) an error analysis shows that it is not possible to achieve the accuracy needed using accelerometers.
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| 24. |
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| 25. |
- Johansson, Carl-Johan, et al.
(författare)
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Sågverksnytt nr 1
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Johansson, Nils, et al.
(författare)
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Möjlighet till utrymning vid brand
- 2012
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Ingår i: Brandskyddshandboken - En handbok för projektering av brandskydd i byggnader. - 1402-3504. ; , s. 75-116
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Bokkapitel (refereegranskat)
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| 27. |
- Johansson-Synnergren, Mats, 1968, et al.
(författare)
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Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study.
- 2004
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 38:1, s. 53-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE--Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN--Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS--C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION--OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.
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| 28. |
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| 29. |
- Jönsen, Andreas, et al.
(författare)
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Direct and indirect costs for systemic lupus erythematosus in Sweden. A nationwide health economic study based on five defined cohorts
- 2016
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 45:6, s. 684-690
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The main objectives of this study were to calculate total costs of illness and cost -driving disease features among patients with systemic lupus erythematosus (SLE) in Sweden. Methods: Five cohorts of well-defined SLE patients, located in different parts of the country were merged. Incident and prevalent cases from 2003 through 2010 were included. The American College of Rheumatology (ACR) classification criteria was used. From the local cohorts, data on demographics, disease activity (SLEDAI 2K), and organ damage (SDI) were collected. Costs for inpatient care, specialist outpatient care and drugs were retrieved from national registries at the National Board of Health and Welfare. Indirect costs were calculated based on sickness leave and disability pensions from the Swedish Social Insurance Agency. Results: In total, 1029 SLE patients, 88% females, were included, and approximately 75% were below 65 years at the end of follow-up, and thus in working age. The mean number of annual specialist physician visits varied from six to seven; mean annual inpatient days were 3.1-3.6, and mean annual sick leave was 123-148 days, all per patient. The total annual cost was 208,555 SEK ($33,369 = 22,941(sic)), of which direct cost was 63,672kr ($10,188 = 7004(sic)) and the indirect cost was 144,883 SEK ($23,181 = 15,937(sic)), all per patient. The costs for patients with short disease duration were higher. Higher disease activity as measured by a SLEDAI 2K score > 3 was associated with approximately 50% increase in both indirect and direct costs. Damage in the neuropsychiatric and musculoskeletal domains were also linked to higher direct and indirect costs, while organ damage in the renal and ocular systems increased direct costs. Conclusion: Based on this study and an estimate of slightly more than 6000 SLE patients in Sweden, the total annual cost for SLE in the country is estimated at $188 million (= 129.5 million (sic)). Both direct (30%) and indirect costs (70%) are substantial. Medication accounts for less than 10% of the total cost. The tax paid national systems for health care and social security in Sweden ensure equal access to health care, sick leave reimbursements, and disability pensions nationwide. Our extrapolated annual costs for SLE in Sweden are therefore the best supported estimations thus far, and they clearly underline the importance of improved management, especially to reduce the indirect costs. (C) 2016 Elsevier Inc. All rights reserved.
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| 30. |
- Jönsson, Göran, et al.
(författare)
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Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency.
- 2007
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 46:7, s. 1133-1139
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse rheurnatological manifestations, organ damage and autoimmune responses in a large cohort of patients (n = 45) with homozygous C2 deficiency (C2D) and long-term follow-up. Methods. Medical records were reviewed and were supplemented with a mailed questionnaire for assessment of cardiovascular disease (CVD) risk factors. Organ damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Causes for disability pensions were investigated. Autoantibodies were determined with established methods. Results. Patients with rheurnatological diseases had systemic lupus erythematosus (SLE, n = 12), undifferentiated connective tissue disease (n=5) or vasculitis (n=3). Judging from annual SLICC/ACR DI, C2D patients with SLE run a similar risk of development of severe disease as other patients with SLE. An increased rate of CVD was observed not explained by Framingham-related risk factors. Disability pensions were mainly related to rheurnatological disease. The prevalence of anti-nuclear antibodies in C2D with SLE and of anti-SS-A was 25% while anti-RNP was found in 45%. Only one patient showed antibodies to dsDNA. Formation of anti-cardiolipin antibodies (aCL) appeared to be increased in C2D despite the absence of an anti-phosphol ipid syndrome. The prevalence of antibodies to the collagen-like region of C1q (C1qCLR) was also remarkably high and was not related to rheumatological manifestations. Conclusions. Severity of SLE in C2D is similar to that of SLE in other patients. Conventional risk factors do not explain the occurrence of CVD in C2D. The high prevalence of aCL and anti-C1qCLR indicates mechanisms through which impaired complement function promotes formation of autoantibodies.
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| 31. |
- Leonard, Dag, et al.
(författare)
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Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants
- 2013
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Ingår i: Circulation: Cardiovascular Genetics. - : BMJ. - 1942-325X .- 1942-3268. ; 72:Suppl. 3, s. 270-270
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Tidskriftsartikel (refereegranskat)abstract
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.
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| 32. |
- Leonard, Dag, 1975-, et al.
(författare)
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Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis.
- 2018
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:7, s. 1063-1069
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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=8.5×10-5) and RA (OR 2.8 (1.4 to 5.6), P=3.8×10-3), meta-analysis (OR 2.5 (2.0 to 2.9), P=3.5×10-7), 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=2.5×10-5) 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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| 33. |
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| 34. |
- Lindholm, Lena, et al.
(författare)
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A closed perfusion system with heparin coating and centrifugal pump improves cardiopulmonary bypass biocompatibility in elderly patients.
- 2004
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Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 78:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory and hemostatic activation, which may contribute to postoperative complications. Our aim was to compare the inflammatory response, coagulation, and fibrinolytic activation between two different perfusion systems: one theoretically more biocompatible with a closed-circuit, complete heparin coating, and a centrifugal pump, and one conventional system with uncoated circuit, roller pump, and a hard-shell venous reservoir. METHODS: Forty-one elderly patients (mean age, 73 +/- 1 years, 66% men) undergoing coronary artery bypass grafting or aortic valve replacement were included in a prospective, randomized study. Plasma concentrations of complement factors (C3a, C4d, Bb, and sC5b-9), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-8), granulocyte degradation products (polymorphonuclear elastase), and markers of coagulation (thrombin-antithrombin) and fibrinolysis (D-dimer, tissue plasminogen activator antigen and tissue plasminogen activator-plasminogen activator inhibitor-1 complex) were measured preoperatively, at bypass during rewarming (35 degrees C), 60 minutes after bypass, and on day 1 after surgery. RESULTS: The mean concentrations of C3a (-39%; p = 0.008), Bb (-38%; p < 0.001), sC5b-9 (-70%; p < 0.001), interleukin-8 (-60%; p = 0.009), polymorphonuclear-elastase (-55%; p < 0.003), and tissue plasminogen activator antigen (-51%; p = 0.012) were all significantly lower in the biocompatible group during rewarming. Sixty minutes after bypass, the mean concentrations of sC5b-9 (-39%; p = 0.006) and polymorphonuclear-elastase (-55%; p < 0.001) were lower in the biocompatible group. CONCLUSIONS: The results suggest that a closed perfusion system with a heparin-coated circuit and a centrifugal pump may improve cardiopulmonary bypass biocompatibility in elderly cardiac surgery patients in comparison with a conventional system.
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| 35. |
- Lindholm, Lena, et al.
(författare)
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Regional oxygenation and systemic inflammatory response during cardiopulmonary bypass: influence of temperature and blood flow variations.
- 2003
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Ingår i: Journal of cardiothoracic and vascular anesthesia. - : Elsevier BV. - 1053-0770. ; 17:2, s. 182-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the role of target temperature (28 degrees or 34 degrees C) in cardiac surgery on regional oxygenation during hypothermia and rewarming and systemic inflammatory response. DESIGN: Prospective, controlled, and randomized clinical study. SETTING: University hospital. PARTICIPANTS: Elderly patients (mean age 70 +/- 2 years) with acquired heart disease with an anticipated bypass time exceeding 120 minutes (n = 30). INTERVENTIONS: The patients were cooled to either 28 degrees C (n = 15) or 34 degrees C (n = 15). At hypothermia, bypass blood flow was reduced twice from full flow (2.4 L/min/m(2) body surface area [BSA]) to 2.0 L/min/m(2). MEASUREMENTS AND MAIN RESULTS: Hepatic and jugular venous oxygen tension and saturation were higher at 28 degrees C than at 34 degrees C. In comparison with the preoperative values, at 28 degrees C hepatic venous values were higher; whereas at 34 degrees C, they were lower. The reduction of pump blood flow during hypothermia, from 2.4 to 2.0 L/min/m(2)was accompanied by reductions of central, jugular, and hepatic oxygenation at both target temperatures. During rewarming, central and regional venous oxygenation decreased irrespective of the preceding temperature. The decrease was most pronounced in hepatic venous blood, with the lowest individual values <10%. Serum concentrations of C3a and IL-6 increased during hypothermia and increased further during rewarming irrespective of the preceding temperature. CONCLUSION: During cardiopulmonary bypass, hypothermia at 28 degrees C increases regional and central venous oxygenation better than at 34 degrees C. In contrast, venous oxygenation decreases during rewarming irrespective of the preceding temperature. No significant difference in the systemic inflammatory response associated with target temperature was detected.
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| 36. |
- Lipcsey, Miklós, 1975-
(författare)
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Pathophysiological, Inflammatory and Haemostatic Responses to Various Endotoxaemic Patterns : An Experimental Study in the Pig
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig. This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels. Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia. Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock. Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function. Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin. Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.
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| 37. |
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| 38. |
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| 39. |
- Lood, Christian, et al.
(författare)
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C1q inhibits immune complex-induced interferon-alpha production in plasmacytoid dendritic cells : a novel link between C1q deficiency and systemic lupus erythematosus pathogenesis
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:10, s. 3081-3090
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: C1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll-like receptor-induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon-alpha (IFNalpha). METHODS: Peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFNalpha production was determined by an immunoassay. RESULTS: C1q significantly inhibited PBMC IFNalpha production induced by RNA-containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFNalpha production induced by ICs and CpG DNA but increased PDC IFNalpha production induced by HSV. The regulatory role of C1q was not specific for IFNalpha but was also seen for interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins. CONCLUSION: Our findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up-regulation of the type I IFN system seen in SLE patients.
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| 40. |
- Lood, Christian, et al.
(författare)
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IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: A possible new treatment?
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:8, s. 2698-2706
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Tidskriftsartikel (refereegranskat)abstract
- Objective Systemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) that stimulate leukocytes through Fc? receptors (Fc?R) with subsequent inflammation. Treatment with endoglycosidase S (EndoS), an IgG glycanhydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. This study was undertaken to investigate whether EndoS affects the proinflammatory properties of ICs and has the potential to be developed as a therapy for SLE. Methods ICs purified from SLE patients or RNA-containing ICs formed in vitro were treated with EndoS and used in several assays reflecting different important features of SLE pathogenesis, such as phagocytosis by polymorphonuclear cells (PMNs) and plasmacytoid dendritic cells (PDCs), complement activation, and interferon-a (IFNa) production by PDCs. Results EndoS treatment abolished all proinflammatory properties of the ICs investigated. This included Fc?R-mediated phagocytosis by PDCs (P = 0.001) and subsequent production of IFNa (P = 0.002), IC-induced classical pathway of complement activation (P = 0.008), chemotaxis, and oxidative burst activity of PMNs (P = 0.002). EndoS treatment also had a direct effect on the molecular structure of ICs, causing decreased IC size and glycosylation. Conclusion Our findings indicate that EndoS treatment has prominent effects on several pathogenetically important IC-mediated events, and suggest that EndoS has the potential to be developed as a novel therapy for SLE.
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| 41. |
- Lood, Christian, et al.
(författare)
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IgG glycan hydrolysis by EndoS diminishes the pro-inflammatory properties of immune complexes from patients with SLE : a possible new treatment?
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:8, s. 2698-2706
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESystemic lupus erythematosus (SLE) is an autoimmune disease with chronic or episodic inflammation in several organ systems, related to the presence of circulating and tissue-deposited immune complexes (ICs) which stimulate leukocytes through FcγRs with subsequent inflammation. Treatment with EndoS, an IgG glycan hydrolyzing bacterial enzyme from Streptococcus pyogenes, has shown beneficial effects in several experimental animal models of chronic inflammatory disease. In the present study we asked if EndoS could affect pro-inflammatory properties of ICs and have the potential to be developed as a therapy in SLE.METHODSICs, purified from SLE patients or RNA-containing ICs formed in vitro, were treated with EndoS and used in several assays reflecting different important parts of SLE pathogenesis such as phagocytosis by polymorphonuclear neutrophils (PMNs) and plasmacytoid dendritic cells (pDCs), complement activation and IFNα production by pDCs.RESULTSOur results demonstrate that EndoS treatment could abolish all pro-inflammatory properties of ICs investigated. This includes FcγR-mediated phagocytosis by pDCs (p<0.0001) and subsequent production of IFNα (p<0.0001), IC-induced classical complement pathway activation (p<0.0001), chemotaxis and oxidative burst activity of PMNs (p=0.002). We could also demonstrate direct effects on the molecular structure of ICs after EndoS treatment with decreased size and glycosylation patterns.CONCLUSIONSProminent effects of EndoS treatment were seen in several pathogenetically important IC-mediated events and our data suggest that EndoS have the potential to be developed as a novel therapy in SLE.
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| 42. |
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| 43. |
- Månsson, Anders, 1977-
(författare)
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Quantum State Analysis : Probability theory as logic in Quantum mechanics
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quantum mechanics is basically a mathematical recipe on how to construct physical models. Historically its origin and main domain of application has been in the microscopic regime, although it strictly seen constitutes a general mathematical framework not limited to this regime. Since it is a statistical theory, the meaning and role of probabilities in it need to be defined and understood in order to gain an understanding of the predictions and validity of quantum mechanics. The interpretational problems of quantum mechanics are also connected with the interpretation of the concept of probability. In this thesis the use of probability theory as extended logic, in particular in the way it was presented by E. T. Jaynes, will be central. With this interpretation of probabilities they become a subjective notion, always dependent on one's state of knowledge or the context in which they are assigned, which has consequences on how things are to be viewed, understood and tackled in quantum mechanics. For instance, the statistical operator or density operator, is usually defined in terms of probabilities and therefore also needs to be updated when the probabilities are updated by acquisition of additional data. Furthermore, it is a context dependent notion, meaning, e.g., that two observers will in general assign different statistical operators to the same phenomenon, which is demonstrated in the papers of the thesis. It is also presented an alternative and conceptually clear approach to the problematic notion of "probabilities of probabilities", which is related to such things as probability distributions on statistical operators. In connection to this, we consider concrete numerical applications of Bayesian quantum state assignment methods to a three-level quantum system, where prior knowledge and various kinds of measurement data are encoded into a statistical operator, which can then be used for deriving probabilities of other measurements. The thesis also offers examples of an alternative quantum state assignment technique, using maximum entropy methods, which in some cases are compared with the Bayesian quantum state assignment methods. Finally, the interesting and important problem whether the statistical operator, or more generally quantum mechanics, gives a complete description of "objective physical reality" is considered. A related concern is here the possibility of finding a "local hidden-variable theory" underlying the quantum mechanical description. There have been attempts to prove that such a theory cannot be constructed, where the most well-known impossibility proof claiming to show this was given by J. S. Bell. In connection to this, the thesis presents an idea for an interpretation or alternative approach to quantum mechanics based on the concept of space-time.
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| 44. |
- Nived, Ola, et al.
(författare)
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High predictive value of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for survival in systemic lupus erythematosus.
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 29:7, s. 1398-1400
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We previously reported high Systemic Lupus International Collaborating Clinics (SLICC) scores in fatal cases of systemic lupus erythematosus (SLE) from our inception cohort. This study was done to clarify if the SLICC damage scores 5 years after diagnosis predicted the outcome. METHODS: We studied 80 patients with SLE (70 women, 10 men), all enrolled and diagnosed during the years 1981 through 1991 in our inception cohort, and all alive 5 years after inclusion into the cohort. In all patients the SLICC/American College of Rheumatology (ACR) damage index (DI) was scored at 5 years after SLE diagnosis, and these scores were tested for predictive value. The outcomes were survival or late mortality within the following median observation period of 7 years. All surviving patients were followed through 1999, and no patient was lost to followup. RESULTS: At study entry, 5 years after the diagnosis of SLE, 37 patients had no damage to score with SLICC. Of the remaining 43 patients, 25 had a score of 1 and 18 had a score of 2 or more. In total, 14 fatalities occurred within 7 years after study entry, 7 among the 18 with initial SLICC/ACR DI of 2 or more compared with 7 fatalities among the 62 with less or no damage (p < 0.01). Cardiovascular or cerebrovascular SLICC/ACR DI items were more common in fatal cases than in survivors (p < 0.001). A SLICC score at 5 years of 2 or more increased the relative risk for fatality by 3.4 (95% CI 1.5-14.4), and had a predictive value of 38%. A SLICC score of 0 at 5 years gave an odds ratio in favor of survival of 0.06 (95% CI 0.0-0.5) and had a predictive value for survival of 97%. During an extended followup for one more year the predictive value of damage for fatalities was even more pronounced (p = 0.003, log-rank). CONCLUSION: SLICC damage scores registered 5 years after SLE diagnosis have a high predictive value for survival during the following median observation time of 7 years. These data provide strong evidence that the items included in the SLICC score are clinically relevant.
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| 45. |
- Nordmark, Gunnel, et al.
(författare)
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Effects of Dehydroepiandrosterone Supplement on Health-related Quality of Life in Glucocorticoid Treated Female Patients with Systemic Lupus Erythematosus
- 2005
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 38:7, s. 531-540
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the efficacy of low dose dehydroepiandrosterone (DHEA) on health-related quality of life (HRQOL) in glucocorticoid treated female patients with systemic lupus erythematosus (SLE). Forty one women ( >or= 5 mg prednisolone/day) were included in a double-blind, randomized, placebo-controlled study for 6 months where DHEA was given at 30 mg/20 mg ( or= 46 years) daily, or placebo, followed by 6 months open DHEA treatment to all patients. HRQOL was assessed at baseline, 6 and 12 months, using four validated questionnaires and the patients' partners completed a questionnaire assessing mood and behaviour at 6 months. DHEA treatment increased serum levels of sulphated DHEA from subnormal to normal. The DHEA group improved in SF-36 "role emotional" and HSCL-56 total score (both p<0.05). During open DHEA treatment, the former placebo group improved in SF-36 "mental health" (p<0.05) with a tendency for improvement in HSCL-56 total score (p=0.10). Both groups improved in McCoy's Sex Scale during active treatment (p<0.05). DHEA replacement decreased high-density lipoprotein (HDL) cholesterol and increased insulin-like growth factor I (IGF-I) and haematocrit. There were no effects on bone density or disease activity and no serious adverse events. Side effects were mild. We conclude that low dose DHEA treatment improves HRQOL with regard to mental well-being and sexuality and can be offered to women with SLE where mental distress and/or impaired sexuality constitutes a problem.
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| 46. |
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| 47. |
- Reid, Sarah, et al.
(författare)
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High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79:3, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison.CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.
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| 48. |
- Reid, Sarah, et al.
(författare)
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High Genetic Risk Score Is Associated with Increased Organ Damage in SLE
- 2017
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Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 69
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with a complex genetic etiology. Over 80 risk genes for SLE have been identified and some genetic variants have demonstrated association with specific disease manifestations, such as STAT4 and nephritis. The overall effect of a patient’s hereditary risk factors on disease severity has so far not been studied. We therefore assessed the relationship between high genetic risk and development of organ damage in SLE.Methods: Patients with SLE, who met at least 4 ACR criteria (n = 1012), were genotyped using a 200K Immunochip SNP Array (Illumina). A genetic risk score (GRS) was assigned to each patient based on the single nucleotide polymorphisms (SNPs) which in previous studies have shown association (p<5×10-8) with SLE according to Morris, et al (Nat Genet, 2016. 48(8): p. 940-6). For 32 loci the SLE GWAS SNP was available on the ImmunoChip. For each SNP, the natural logarithm of the odds ratio (OR) for SLE susceptibility was multiplied by the number of risk alleles in each individual. The sum of all products for each patient was defined as the GRS. Information regarding organ damage according to Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC-DI), disease manifestations, antibody profile, medication, current disease activity, age at diagnosis and sex was retrieved from medical records. Statistical analyzes were performed using Statistica 13.2 (Statsoft).Results: In an ordinal regression model, with SLICC-DI (0, 1, 2, 3, 4 and >4 points) as outcome and age and GRS as independent variables, an association was found between GRS and SLICC-DI (OR1.16 (1.03-1.31), p=0.015). The relationship was more pronounced for patients under 60 years of age (OR1.30 (1.11-1.52) p=7.1×10-4). Using a linear regression model, a negative relationship was observed between GRS and age at diagnosis (β = -0.13, p=1.5×10-5).When analyzing the 11 SLE criteria (ACR-82) using a logistic regression model associations were observed between GRS and nephritis (OR 1.26 (1.09-1.45), p=0.0015), the immunological criteria (OR 1.31 (1.13-1.51), p = 3.2×10-4) and arthritis (OR 0.84 (0.71-1.00), p=0.044). A high GRS was also associated with presence of anti-dsDNA (OR 1.37 (1.15-1.62), p=9.4×10-7) and low complement levels (OR 1.32 (1.03-1.68), p=0.044). No association was observed between GRS and disease activity at the time of follow-up and there was no difference in GRS between men and women with SLE.Conclusion: In patients with SLE, there is an association between a high genetic risk score and early disease onset. In addition, patients with high genetic risk scores have a higher risk of developing permanent organ damage compared to individuals with fewer risk genes. Our findings indicate that genetic profiling of patients with SLE may provide a tool for predicting severity of the disease.
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| 49. |
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| 50. |
- Sandling, Johanna K., et al.
(författare)
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Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.
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