| 1. |
- Idborg, Helena, et al.
(författare)
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STRATIFICATION OF SLE PATIENTS FOR IMPROVED DIAGNOSIS AND TREATMENT
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72, s. A80-A80
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background. Systemic autoimmune diseases (SAIDs) affect about 2% of the population in Western countries. Sufficient diagnostic criteria are lacking due to the heterogeneity within diagnostic categories and apparent overlap regarding symptoms and patterns of autoantibodies between different diagnoses. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesise that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies.Objectives. Our goal is to find new biomarkers to be used for the identification of more homogenous patient populations for clinical trials and to identify sub-groups of patients with high risk of for example cardiovascular events.Methods. In this study we have utilised 320 SLE patients from the Karolinska lupus cohort and 320 age and gender matched controls. The SLE cohort was characterised based on clinical, genetic and serological data and combined by multivariate data analysis in a systems biology approach to study possible subgroups. A pilot study was designed to verify and investigate suggested subgroups of SLE. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), i.e., a “Sjögren-like” group. The other group was defined as being negative for SSA and SSB antibodies but positive in the LAC test.i.e. an “APS-like” group. EDTA-plasma from selected patients in these two groups and controls were analysed using a mass spectrometry (MS) based proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data.Results. Our pilot study showed that differences in levels of proteins and metabolites could separate disease groups from population controls. The profile/pattern of involved factors in the complement system supported a division of SLE in two major subgroups, although each individual factor was not significantly different between subgroups. Complement factor 2 (C2) and membrane attack complex (MAC) were analysed in the entire cohort with complementary methods and C2 verifies our results while the levels of MAC did not differ between SLE subgroups. The generated metabolomics data clearly separated SLE patients from controls in both gas chromatography (GC)-MS and liquid chromatography (LC)-MS data. We found for example that tryptophan was lower in the SLE patients compared to controls.Conclusions. Our systems biology approach may lead to a better understanding of the disease and its pathogenesis, and assigning patients into subgroups will result in improved diagnosis and better outcome measures of SLE.
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| 2. |
- Srivastava, Vaibhav, et al.
(författare)
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OnPLS integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic hipI- superoxide dismutase Populus plants
- 2013
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Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.RESULTS: The main categories that appear to be significantly influenced in the transgenic plants were pathways related to redox regulation, carbon metabolism and protein degradation, e.g. the glycolysis and pentose phosphate pathways (PPP). The results provide system-level information on ROS metabolism and responses to oxidative stress, and indicate that some initial responses to oxidative stress may share common pathways.CONCLUSION: The proposed data evaluation strategy shows an efficient way of compiling complex, multi-platform datasets to obtain significant biological information.
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| 3. |
- Peolsson, Michael, et al.
(författare)
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Modelling human musculoskeletal functional movements using ultrasound imaging
- 2010
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Ingår i: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342 .- 1471-2342. ; 10, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A widespread and fundamental assumption in the health sciences is that muscle functions are related to a wide variety of conditions, for example pain, ischemic and neurological disorder, exercise and injury. It is therefore highly desirable to study musculoskeletal contributions in clinical applications such as the treatment of muscle injuries, post-surgery evaluations, monitoring of progressive degeneration in neuromuscular disorders, and so on.The spatial image resolution in ultrasound systems has improved tremendously in the last few years and nowadays provides detailed information about tissue characteristics. It is now possible to study skeletal muscles in real-time during activity.Methods: The ultrasound images are transformed to be congruent and are effectively compressed and stacked in order to be analysed with multivariate techniques. The method is applied to a relevant clinical orthopaedic research field, namely to describe the dynamics in the Achilles tendon and the calf during real-time movements.Results: This study introduces a novel method to medical applications that can be used to examine ultrasound image sequences and to detect, visualise and quantify skeletal muscle dynamics and functions.Conclusions: This new objective method is a powerful tool to use when visualising tissue activity and dynamics of musculoskeletal ultrasound registrations.
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| 4. |
- Peterson, Gunnel, et al.
(författare)
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Altered ventral neck muscle deformation for individuals with whiplash associated disorder compared to healthy controls : A case-control ultrasound study
- 2015
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Ingår i: Manual Therapy. - : Elsevier. - 1356-689X .- 1532-2769. ; 20:2, s. 319-327
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown altered neck muscle function in individuals with chronic whiplash associated disorder (WAD). However, we lack real-time investigations with non-invasive methods that can distinguish between the different ventral neck muscle layers. This study investigated deformations and deformation rates in the sternocleidomastoid (SCM), longus capitis (Lcap), and longus colli (Lco) muscles with real-time ultrasonography. Twenty-six individuals with WAD were compared with 26 controls, matched for age and sex. Ultrasound imaging of the SCM, Lcap, and Lco were recorded during 10 repetitive arm elevations. The first and tenth arm elevations were post-process analyzed with speckle tracking. There were few significant differences in the deformations or deformation rates in the SCM, Lcap, and Lco between the WAD and control group. In controls, deformations and deformation rates showed linear positive relationships between SCM/Lcap, SCM/Lco, and Lcap/Lco which increased from the first arm elevation (R-2 = 0.14-0.70); to the tenth arm elevation (R-2 = 0.51-0.71). The WAD group showed similar or weaker linear relationship (R-2 < 0.19) during the tenth compared to the first (R-2 < 0.44) arm elevation except for deformations in Lcap/Lco (R-2 = 0.13-0.57). This result indicated that deformations and deformation rates in one muscle were correlated by similar deformations and deformation rates in other neck muscles in the control group, but this interplay between muscles was not found in the WAD group. (C) 2014 Elsevier Ltd. All rights reserved.
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| 5. |
- Peterson, Gunnel, et al.
(författare)
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Changes in dorsal neck muscle function in individuals with chronic whiplash-associated disorders : a real-time ultrasound case-control study
- 2016
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Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 42:5, s. 1090-1102
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Tidskriftsartikel (refereegranskat)abstract
- Impaired neck muscle function leads to disability in individuals with chronic whiplash-associated disorder (WAD), but diagnostic tools are lacking. In this study, deformations and deformation rates were investigated in five dorsal neck muscles during 10 arm elevations by ultrasonography with speckle tracking analyses. Forty individuals with chronic WAD (28 women and 12 men, mean age = 37 y) and 40 healthy controls matched for age and sex were included. The WAD group had higher deformation rates in the multifidus muscle during the first (p < 0.04) and 10th (only women, p < 0.01) arm elevations compared with the control group. Linear relationships between the neck muscles for deformation rate (controls: R-2 = 0.24-0.82, WAD: R-2 = 0.05-0.74) and deformation of the deepest muscles (controls: R-2 = 0.61-0.32, WAD: R-2 = 0.15-0.01) were stronger for women in the control group versus women with WAD, indicating there is altered interplay between dorsal neck muscles in chronic WAD.
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| 6. |
- Peterson, Gunnel, et al.
(författare)
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Novel insights into the interplay between ventral neck muscles in individuals with whiplash-associated disorders
- 2015
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 5:15289
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Tidskriftsartikel (refereegranskat)abstract
- Chronic whiplash-associated disorder (WAD) is common after whiplash injury, with considerable personal, social, and economic burden. Despite decades of research, factors responsible for continuing pain and disability are largely unknown, and diagnostic tools are lacking. Here, we report a novel model of mechanical ventral neck muscle function recorded from non-invasive, real-time, ultrasound measurements. We calculated the deformation area and deformation rate in 23 individuals with persistent WAD and compared them to 23 sex-and age-matched controls. Multivariate statistics were used to analyse interactions between ventral neck muscles, revealing different interplay between muscles in individuals with WAD and healthy controls. Although the cause and effect relation cannot be established from this data, for the first time, we reveal a novel method capable of detecting different neck muscle interplay in people with WAD. This non-invasive method stands to make a major breakthrough in the assessment and diagnosis of people following a whiplash trauma.
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| 7. |
- Rosendal, Ebba, et al.
(författare)
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Serine Protease Inhibitors Restrict Host Susceptibility to SARS-CoV-2 Infections
- 2022
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019, COVID-19, is a complex disease with a wide range of symptoms from asymptomatic infections to severe acute respiratory syndrome with lethal outcome. Individual factors such as age, sex, and comorbidities increase the risk for severe infections, but other aspects, such as genetic variations, are also likely to affect the susceptibility to SARS-CoV-2 infection and disease severity. Here, we used a human 3D lung cell model based on primary cells derived from multiple donors to identity host factors that regulate SARS-CoV-2 infection. With a transcriptomics-based approach, we found that less susceptible donors show a higher expression level of serine protease inhibitors SERPINA1, SERPINE1, and SERPINE2, identifying variation in cellular serpin levels as restricting host factors for SARS-CoV-2 infection. We pinpoint their antiviral mechanism of action to inhibition of the cellular serine protease, TMPRSS2, thereby preventing cleavage of the viral spike protein and TMPRSS2-mediated entry into the target cells. By means of single-cell RNA sequencing, we further locate the expression of the individual serpins to basal, ciliated, club, and goblet cells. Our results add to the importance of genetic variations as determinants for SARS-CoV-2 susceptibility and suggest that genetic deficiencies of cellular serpins might represent risk factors for severe COVID-19. Our study further highlights TMPRSS2 as a promising target for antiviral intervention and opens the door for the usage of locally administered serpins as a treatment against COVID-19.
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| 8. |
- Bylesjö, Max, et al.
(författare)
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Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
- 2009
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
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| 9. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 10. |
- Checa, A., et al.
(författare)
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Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus : a cross-sectional study
- 2017
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Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 26:10, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus.Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease.Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment.Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.
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