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  • 1.
    Aksel Jacobsen, Freja
    et al.
    Novo Nordisk A/S, Bagsværd, Denmark.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    Inhibitors of intracellular enzymes for treatment of multiple sclerosis2019In: Atlas of ScienceArticle, review/survey (Other (popular science, discussion, etc.))
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  • 2.
    Aksel Jacobsen, Freja
    et al.
    University of Copenhagen, Copenhagen, Denmark & Novo Nordisk A/S, Bagsværd, Denmark.
    Scherer, Alexander N.
    Yale University School of Medicine, New Haven, CT, USA.
    Mouritsen, Jeppe
    University of Copenhagen, Copenhagen, Denmark & Novozymes A/S, Bagsværd, Denmark.
    Bragadóttir, Hera
    University of Copenhagen, Copenhagen, Denmark & Xelia Pharmaceuticals A/S, Copenhagen, Denmark.
    Bäckström, B. Thomas
    Novo Nordisk A/S, Måløv, Denmark & BTB Pharma, Malmö, Sweden.
    Sardar, Samra
    University of Copenhagen, Copenhagen, Denmark.
    Holmberg, Dan
    Lund University, Malmö, Sweden.
    Koleske, Anthony J.
    Yale University School of Medicine, New Haven, CT, USA.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). University of Copenhagen, Copenhagen, Denmark.
    A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation2018In: Journal of Neuroimmune Pharmacology, ISSN 1557-1890, E-ISSN 1557-1904, Vol. 13, no 2, p. 265-276Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis is a neuroinflammatory degenerative disease, caused by activated immune cells infiltrating the CNS. The disease etiology involves both genetic and environmental factors. The mouse genetic locus, Eae27, linked to disease development in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis, was studied in order to identify contributing disease susceptibility factors and potential drug targets for multiple sclerosis. Studies of an Eae27 congenic mouse strain, revealed that genetic variation within Eae27 influences EAE development. The Abl2 gene, encoding the non-receptor tyrosine kinase Arg, is located in the 4,1 megabase pair long Eae27 region. The Arg protein plays an important role in cellular regulation and is, in addition, involved in signaling through the B- and T-cell receptors, important for the autoimmune response. The presence of a single nucleotide polymorphism causing an amino acid change in a near actin-interacting domain of Arg, in addition to altered lymphocyte activation in the congenic mice upon immunization with myelin antigen, makes Abl2/Arg a candidate gene for EAE. Here we demonstrate that the non-synonymous SNP does not change Arg’s binding affinity for F-actin but suggest a role for Abl kinases in CNS inflammation pathogenesis by showing that pharmacological inhibition of Abl kinases ameliorates EAE, but not experimental arthritis. © 2018 The Author(s)

  • 3.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). Köpenhamns universitet, Köpenhamn, Danmark.
    Abl-tyrosinkinaser och multipel skleros2018In: BestPractice, Vol. 6, no 24, p. 14-16Article, review/survey (Other academic)
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  • 4.
    Andersson, Åsa
    et al.
    Halmstad University, School of Business, Innovation and Sustainability, The Rydberg Laboratory for Applied Sciences (RLAS). University of Copenhagen, Copenhagen, Denmark.
    Aksel Jacobsen, Freja
    Copenhagen University, Copenhagen, Denmark.
    B-cells and Inflammation in the Absence of the Abelson Related Gene (Arg)2016In: Journal of Clinical & Cellular Immunology, E-ISSN 2155-9899, Vol. 7, no 6, article id 1000470Article in journal (Refereed)
    Abstract [en]

    The Abelson non-receptor tyrosine kinases, c-Abl and Arg, are important regulators of cellular processes in cancer, inflammation, infection, and neuronal dynamics. Recent research on the role for these kinases in processes involving interactions with the cytoskeleton or signaling molecules, may lead to further insight into the pathogenesis of a variety of disorders, including chronic inflammatory diseases. In a mouse model for multiple sclerosis, we recently reported that Arg deficient mice develop T-cell mediated autoimmune neuro-inflammation with the same severity as littermate controls, but display a different B-cell phenotype upon immunization. Here we comment on these results and discuss the role for Arg in B-cell activation and homeostasis.

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  • 5.
    Andersson, Åsa
    et al.
    Halmstad University, School of Business, Innovation and Sustainability.
    Haglund, Emma
    Halmstad University, School of Business, Innovation and Sustainability. FoU Spenshult Spenshult Research and Development Centre, Spenshult Research and Development Centre, Halmstad, Sweden; Lund University, Dept. of Clinical Sciences, Section of Rheumatology, Lund, Sweden.
    Berthold, Emma
    Halmstad University, School of Business, Innovation and Sustainability.
    Mogard, Elisabeth
    Lund University, Lund, Sweden.
    Torell, Anna
    Ängelholm Hospital, Ängelholm, Sweden.
    Olsson, M. Charlotte
    Halmstad University, School of Business, Innovation and Sustainability.
    Serum Protein Response To A Single High-Intensity Interval Training Bout – Comparison Between Individuals With Spondyloarthritis And Healthy Controls2022In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 81, no Suppl 1, p. 780-781Article in journal (Refereed)
  • 6.
    Andersson, Åsa
    et al.
    Halmstad University, School of Business, Innovation and Sustainability.
    Olsson, M. Charlotte
    Halmstad University, School of Business, Innovation and Sustainability.
    Torell, Anna
    Halmstad University, School of Business, Innovation and Sustainability. Ängelholm hospital, Dept. of Rehabilitation.
    Mogard, Elisabeth
    Rheumatology, Dept. of Clinical Sciences, Lund University, Skåne University Hospital.
    Haglund, Emma
    Halmstad University, School of Business, Innovation and Sustainability. Spenshult Research and Development Centre, Halmstad.
    Effects on serum protein levels from one bout of high intensity interval training in individuals with axial spondyloarthritis and controlsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the axial skeleton causing pain, inflammation, and stiffness. Individuals with axSpA are at greater risk of developing cardiovascular disease, which can be counteracted by physical activity. High-intensity interval training (HIIT) has been shown to improve cardiovascular health, but the effect on disease activity and the level of inflammation in axSpA has been less studied. With the aim of investigating how levels of inflammatory cytokines, myokines, and protein markers for bone metabolism are acutely affected by one bout of HIIT, we studied serum from individuals with axSpA and healthy controls (HC). Methods: Ten participants with axSpA and 11 age- and sex-matched HC performed a single HIIT bout on a cycle ergometer: 4x4 minutes intervals with three minutes active rest in between. Blood samples were taken before and one hour after the HIIT bout. Serum proteins (IL-6, IL-17, IL-18, TNFa, CXCL-10, VEGF-A, BDNF, DKK-1, osteoprotegerin, osteocalcin, osteopontin, BMP-7, CRP) were analyzed with a Luminex system or ELISA. Descriptive data are presented as mean with standard deviation. A two-way ANOVA was used for comparisons. Results: A main effect from baseline to one hour post HIIT showed that both groups had a significant increase in serum levels (pg/ml) of IL-6: axSpA 2.2 (3.0) to 3.2 (1.8) and HC 0.4 (0.4) to 1.9 (2.0), p=0.03. VEGF-A (pg/ml) was significantly lower in the axSpA group: 159 (138) vs. HC 326 (184), p=0.03, but was not affected by the HIIT bout. BMP-7 (ng/ml) increased in both groups after the HIIT: axSpA 61.6 (13.1) to 75.2 (20.0) and HC 64.6 (20.8 to 75.0 (17.8), p<0.001. For the other proteins analyzed, there were no significant differences in serum concentrations between individuals with axSpA and HC, or within the two groups before and after one bout of HIIT. Conclusions: One acute bout of HIIT significantly increases the serum concentrations of IL-6 and BMP-7 after 1 hour in both individuals with axSpA and HC. 

  • 7.
    Andersson, Åsa
    et al.
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). Department of Drug Design and Pharmacology, Copenhagen University, Copenhagen, Denmark.
    Sardar, Samra
    Nordic Bioscience, Copenhagen, Denmark.
    A transcriptional regulator controlling severity in experimental arthritis2019In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 78, no Suppl. 2, p. 667-667, article id FRI0011Article in journal (Refereed)
    Abstract [en]

    Background: Susceptibility to Rheumatoid Arthritis (RA) is dependent on complex interactions among genetic and environmental factors. Protein candidates and their role in pathways leading to chronic inflammation of the joints, in addition to their potential as drug targets, can be revealed with the help of experimental models for disease (1). From the results of functional genetic studies, we have recently shown that the T-box gene, TBX3, is a candidate gene in Collagen Induced Arthritis (CIA), an experimental model for RA (2). TBX3 encodes a transcriptional regulator involved in differentiation of several organs, including bone, during embryonic development. It has, in addition, been demonstrated important in oncogenesis (3). Our studies suggest that TBX3 has a role in B-cell activation and is important for the severity of disease in the CIA model (2). Objectives: The objective of this project is to understand the role for the transcriptional regulator TBX3 in development of RA. Methods: Bioinformatics based comparative studies of mouse and human alleles in the regulatory region of TBX3. CRISPR/Cas9-introduced deletions and base modifications in human B-cell lines. Activation of genetically modified B-cells in vitro, followed by analyses of proliferative response and antibody production. Results: Studies of CIA development in mice with single nucleotide polymorphisms (SNPs) in the regulatory region of Tbx3 revealed a significant difference in severity of arthritis. In line with this, the anti-collagen type II antibody titers were shown substantially higher in mice with more severe arthritis, even before onset of disease. In addition, preliminary data shows that the proliferative response to Type II collagen upon re-challenge of lymph node cells in vitro is higher in these mice, suggesting a more active response to the disease-inducing antigen. Because the TBX3 gene is conserved between mouse and human, we are investigating whether similar genetic variations are found in the regulatory region of the human TBX3 gene and whether the putative genetic variation would lead to a distinct B-cell phenotype upon activation in vitro. Conclusion: We suggest that the oncoprotein TBX3 is a novel candidate contributing to disease severity in experimental arthritis. Investigations of genetic variation in the TBX3 gene and its role in the activation of human B-cells will reveal whether this protein is a candidate for influencing also development of RA.

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  • 8.
    Hansen, Kirstine M.
    et al.
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Jäger, Anna K.
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Andersson, Åsa
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Mo-clay for treatment of psoriasis2016In: Planta Medica, Stuttgart: Georg Thieme Verlag KG, 2016, Vol. 82 (S 01), article id P550Conference paper (Refereed)
    Abstract [en]

    Mo-clay was used by German doctors to treat injured soldiers' wounds during the First World War. Today, there are anecdotal cases of mo-clay being beneficial for patients suffering from psoriasis, a chronic, inflammatory disease. There are several histological features in the psoriatic skin, including acanthosis, hyperkeratosis, pararkeratosis and a loss of granular layer. Mo-clay is a unique marine deposit, an Eocene clayed diatomite. It was formed 54 million years ago from deposits of single-celled algae along with clay minerals and volcanic ash. The major elements are silicon, aluminium and iron. It is found in Denmark and Germany. As mo-clay had been used to treat wounds, it was tested for antibacterial activity. Mo-clay did not show any anti-bacterial activity against a battery of Gram-positive and -negative bacteria. Mo-clay showed stimulation of cell proliferation at concentrations 39 – 78 µg/ml in splenic mouse lymphocytes, and at 156 µg/ml in HaCat cells, whereas an inhibition of proliferation was observed at 313 µg/ml. Mo-clay was tested for anti-psoriatic activity in vivo using the mouse tail test [1]. This model can be used to investigate agents for effect on psoriasis, since the adult mouse tail has regions of both orthokeratosis and parakeratosis. Mo-clay induced orthokeratosis and showed a significant increase in epidermis thickness. The results suggest that mo-clay may have anti-psoriatic effects.

  • 9.
    Jacobsen, Freja A.
    et al.
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark & Novo Nordisk A/S, Gentofte, Denmark.
    Hulst, Camilla
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark & Novo Nordisk A/S, Gentofte, Denmark.
    Bäckström, Thomas
    Novo Nordisk A/S, Måløv, Denmark & BTB Pharma, Malmö, Sweden.
    Koleske, Anthony J.
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, USA.
    Andersson, Åsa
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Arg Deficiency Does not Influence the Course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced Experimental Autoimmune Encephalomyelitis2016In: Journal of Clinical & Cellular Immunology, E-ISSN 2155-9899, Vol. 7, no 3, article id 1000420Article in journal (Refereed)
    Abstract [en]

    Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has been extensively studied in immune activation, roles for Arg are incompletely characterized. To investigate the role for Arg in experimental autoimmune encephalomyelitis, we studied disease development in Arg-/- mice.

    Methods: Arg-/- and Arg+/+ mice were generated from breeding of Arg+/- mice on the C57BL/6 background. Mice were immunized with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide and disease development recorded. Lymphocyte phenotypes of wild type Arg+/+ and Arg-/- mice were studied by in vitro stimulation assays and flow cytometry.

    Results: The breeding of Arg+/+ and Arg-/- mice showed skewing in the frequency of born Arg-/- mice. Loss of Arg function did not affect development of experimental autoimmune encephalomyelitis, but reduced the number of splenic B-cells in Arg-/- mice following immunization with MOG peptide.

    Conclusions: Development of MOG-induced experimental autoimmune encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development. © 2016 Jacobsen FA, et al.

  • 10.
    Jakobsson, Trille
    et al.
    Lund University, Health Science.
    Lauruschkus, Katarina
    Lund University, Health Science.
    Holmberg, Robert
    Lund University, Dept. of Psychology.
    Andersson, Åsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Tornberg, Åsa
    Lund University, Health Science.
    Physical Activity objectively assessed over a Year in Children and Adolescents with Cerebral Palsy who are Non-Ambulant using ActiGraph GT3X Accelerometer2024Conference paper (Refereed)
    Abstract [en]

    Introduction: Children gain increased health and wellbeing by participating in physical activity (PA). In children and adolescents with cerebral palsy who are non-ambulant (children with CP-NA), levels of PA have been indicated to be lower compared to children and adolescents without physical disabilities. However, research on PA in children with CP-NA is limited. Therefore, this study aims to evaluate objectively assessed PA over the course of one year when using ActiGraph GT3X accelerometer in children with CP-NA. 

    Participants and methods: Accelerometer data were retrieved from 32 children with CP-NA (4 - 17 years) in Region Skane, Sweden. Participants wore the ActiGraph GT3X accelerometer all waking hours for up to four periods of seven consecutive days over a year. Statistically sensitivity analyses were run to explore differences in PA between subtypes of cerebral palsy and GMFCS level IV and V. 

    Results: In total 481 days and 85 periods of valid accelerometer data were obtained. Light PA was statically significantly higher for children with dyskinetic CP-NA compared to spastic CP-NA (median (IQR) 57 (37.42-88.1) vs. 34.42 (20.42-55.96), p = <0.001). Light PA (median (IQR) 57 (36.67-88.5) vs. 25.42 (17-38.75), p = <0.001) and moderate to vigorous PA (median (IQR) 1.83 (1-4.17) vs. 1.67 (0.67-2), p = <0.001) were statically significantly higher for children with CP-NA GMFCS level IV compared to level V. 

    Conclusion: Preliminary results indicate differences in PA levels between subtype of cerebral palsy and GMFCS level. Further analyses to explore potential differences in PA over the year will be run.

  • 11.
    Lundström, Petra
    et al.
    Lund University, Lund, Sweden.
    Lauruschkus, Katarina
    Lund University, Lund, Sweden.
    Andersson, Åsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Tornberg, Åsa B.
    Lund University, Lund, Sweden.
    Acute Response to One Bout of Dynamic Standing Exercise on Blood Glucose and Blood Lactate Among Children and Adolescents With Cerebral Palsy Who are Nonambulant2022In: Pediatric Exercise Science, ISSN 0899-8493, E-ISSN 1543-2920, Vol. 34, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the acute exercise effects of dynamic standing exercise (DyS) on blood glucose and blood lactate among children and adolescent with cerebral palsy (CP) who are non-ambulant. 

    Methods: Twenty-four participants with CP who are non-ambulant performed 30 minutes of DyS using a motorized device enabling assisted passive movements in an upright weight-bearing position. Capillary blood-samples were taken from the fingertip for measurement of blood glucose and blood lactate at rest and at the end of exercise. 

    Results: At rest, the participants had hyperlactatemia that was unaffected after exercise presented as median and interquartile range at rest 1.8 [1.3:2.7] mmol/L and after exercise 2.0 [1.1:2.5] mmol/L. Children and adolescents with GMFCS-E&R V had higher lactate levels at rest (2.5 [1.8:2.9] vs 1.4 [1.0:2.0]; p=0.030) and after exercise (2.3 [2.0:2.6] vs 1.2 [0.9:2.2]; p=0.032) compared to children and adolescents with GMFCS-E&R IV respectively. A statistically significant larger decrease in blood lactate levels after exercise was observed in children and adolescents with higher resting blood lactate levels (rho=0.56;p=0.004). There were no statistically significant changes in blood glucose. 

    Conclusions: Forty percent of the participants had mild hyperlactatemia at rest and participants with the highest blood lactate levels at rest had the greatest decrease in blood lactate levels after one bout of exercise. Children and adolescents with classified into higher level of GMFCS-E&R had higher blood lactate levels. More studies are needed on how to prevent chronically high resting levels of lactate with exercise in children with CP who are non-ambulant. 

  • 12.
    Olsson, M. Charlotte
    et al.
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    Fälth, Jenny
    Halmstad University, School of Business, Engineering and Science.
    Ahlebrand, August
    Halmstad University, School of Business, Engineering and Science.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    Haglund, Emma
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). Spenshult Research and Development Center, Halmstad, Sweden.
    Bench press muscle activation with triceps brachii pre-exhaustion in females and males2019In: Journal of Sports Sciences, ISSN 0264-0414, E-ISSN 1466-447X, Vol. 37, no Supp1, p. 71-72, article id D2.P6.Article in journal (Refereed)
  • 13.
    Sardar, Samra
    et al.
    University of Copenhagen, Copenhagen, Denmark.
    Alish, Kerr
    University of Copenhagen, Copenhagen, Denmark & Pfizer Pharmaceuticals, Dublin, Ireland.
    Vaartjes, Daniëlle
    University of Copenhagen, Copenhagen, Denmark & Karolinska Institute, Stockholm, Sweden.
    Voetmann, Mathilde Emilie
    University of Copenhagen, Copenhagen, Denmark & Biogen Denmark A/S, Hillerød, Denmark.
    Moltved, Emilie Riis
    University of Copenhagen, Copenhagen, Denmark & QuintilesIMS, North Carolina, USA.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). University of Copenhagen, Copenhagen, Denmark.
    A novel candidate for genetic control of Collagen Induced Arthritis is involved in transcriptional regulation of B-cell proliferation2017Conference paper (Other academic)
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    Abstract IFRA
  • 14.
    Sardar, Samra
    et al.
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Andersson, Åsa
    Dept. of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
    Old and new therapeutics for Rheumatoid Arthritis: in vivo models and drug development2016In: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 38, no 1, p. 2-13Article in journal (Refereed)
    Abstract [en]

    Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing rodent models for Rheumatoid Arthritis in the context of how these models have been utilized for developing established therapy in Rheumatoid Arthritis and, furthermore, the present use of animal models for studies of novel drug candidates. We have studied the literature in the field for the use of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although a single Rheumatoid Arthritis in vivo model cannot mirror the complexity of disease development, there exist a number of good animal models for Rheumatoid Arthritis, each defining some parts in disease development, which are useful for studies of drug response. We find that many of the established drugs were not tested in in vivo models before being used in the clinic, but rather animal models have been subsequently used to find mechanisms for efficacy. Finally, we report a number of novel drugs, tested in preclinical in vivo models, presently in clinical trials. © 2016 Taylor and Francis.

  • 15.
    Sardar, Samra
    et al.
    University of Copenhagen, Copenhagen, Denmark & Nordic Bioscience A/S, Copenhagen, Denmark.
    Kanne, Katrine
    University of Copenhagen, Copenhagen, Denmark & Novartis International AG, Copenhagen, Denmark.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS). University of Copenhagen, Copenhagen, Denmark.
    Analysis of polymorphisms in the mediator complex subunit 13-like (Med13L) gene in the context of immune function and development of experimental arthritis2018In: Archivum Immunologiae et Therapiae Experimentalis, ISSN 0004-069X, E-ISSN 1661-4917, Vol. 66, no 5, p. 365-377Article in journal (Refereed)
    Abstract [en]

    The Mediator complex subunit 13-like (MED13L) protein is part of the multi-protein mediator complex and plays an important role in gene transcription. Polymorphisms in the MED13L gene have been linked to congenital heart anomalies and intellectual disabilities. Despite recent evidence of indirect links of MED13L to cytokine release and inflammation, impact of genetic variations in MED13L on immune cells remains unexplored. The B10.RIII and RIIIS/J mouse strains vary in susceptibility to induced experimental autoimmune disease models. From sequencing data of the two mouse strains, we identified six polymorphisms in the coding regions of Med13l. By using congenic mice, we studied the effect of these polymorphisms on immune cell development and function along with susceptibility to collagen-induced arthritis, an animal model for Rheumatoid Arthritis (RA). Combining in vivo disease data, in vitro functional data, and computational analysis of the reported non-synonymous polymorphisms, we report that genetic polymorphisms in Med13l do not affect the immune phenotype in these mice and are predicted to be non-disease associated. © The Author(s) 2018

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  • 16.
    Sardar, Samra
    et al.
    Nordic Bioscience A/S, Copenhagen, Denmark.
    Kerr, Alish
    Nuritas, Dublin, Ireland.
    Vaartjes, Daniëlle
    Karolinska Institutet, Stockholm, Sweden.
    Moltved, Emilie Riis
    IQVIA Denmark, Copenhagen, Denmark.
    Karosiene, Edita
    Novo Nordisk A/S, Copenhagen, Denmark.
    Gupta, Ramneek
    Technical University of Denmark, Lyngby, Denmark.
    Andersson, Åsa
    Halmstad University, School of Business, Engineering and Science, The Rydberg Laboratory for Applied Sciences (RLAS).
    The oncoprotein TBX3 is controlling severity in experimental arthritis2019In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 21, no 1, article id 16Article in journal (Refereed)
    Abstract [en]

    Background: Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease as well as in experimental models for disease. The T-box protein 3 is a transcriptional repressor essential during early embryonic development, in the formation of bone and additional organ systems, and in tumorigenesis.

    Methods: With the aim to find novel genes important for autoimmune inflammation, we have performed genetic studies of collagen-induced arthritis, a mouse experimental model for Rheumatoid Arthritis.

    Results: We show that a small genetic fragment on mouse chromosome 5, including Tbx3 and three additional protein-coding genes, is linked to severe arthritis and high titers of anti-collagen antibodies. Gene expression studies have revealed differential expression of Tbx3 in B-cells, where low expression was accompanied by a higher B-cell response upon B-cell receptor stimulation in vitro. Furthermore, we show that serum TBX3 levels rise concomitantly with increasing severity of CIA.

    Conclusions: From these results, we suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of collagen-induced arthritis and high titers of autoantibodies. We also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.

  • 17.
    Sardar, Samra
    et al.
    University of Copenhagen, Copenhagen, Denmark.
    Vartjes, Daniëlle
    Karolinska Institute, Stockholm, Sweden.
    Voetmann, Mathilde
    University of Copenhagen.
    Andersson, Åsa
    University of Copenhagen, Copenhagen, Denmark.
    Novel candidates for genetic control of Collagen INduced Arthritis are involved in transcriptional regulation of B-cell proliferation2017Conference paper (Refereed)
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    Publ abstract FOCIS 2017
  • 18.
    Torell, Anna
    et al.
    Halmstad University, School of Business, Innovation and Sustainability.
    Olsson, M. Charlotte
    Halmstad University, School of Business, Innovation and Sustainability.
    Andersson, Åsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Malm, Karina
    Åberg, Ida
    Wiking, Emelie
    Haglund, Emma
    Halmstad University, School of Business, Innovation and Sustainability.
    Effects of a digital-based high-intensity interval training (HIIT) intervention in individuals with axial spondyloarthritis: – a randomized controlled pilot study (RCT)2023Conference paper (Refereed)
    Abstract [en]

    Background

    Physical exercise is an important treatment for individuals with axial spondyloarthritis (axSpA). Although high-intensity training (HIT) has been shown to reduce disease symptoms and risk of comorbidity without exacerbating disease activity (1), compliance tends to decrease over time. Increased knowledge is needed on how to optimize and tailor individual exercise programs for continued regular exercising and improved health.

    Objective

    To study the effects of HIT on aerobic capacity, body composition, disease activity, physical function, health status and fatigue in individuals with axSpA after a 12-week intervention supported by digital coaching.

    Methods

    Twenty-two individuals (women, n=12), recruited from two rheumatology clinics in southern Sweden, were randomized to a HIT intervention group (HG; n=11) or a control group (CG; n=11). The HG completed three HIT sessions/week, including two interval training sessions (4x4 min), in self-selected activities for 12 weeks. The individuals in the HG were individually coached and had regular support from a physical therapist primarily by digital coaching. The CG continued exercising as usual. Assessment of aerobic capacity (VO2max), body composition (BMI and visceral fat area [cm2]), disease activity (CRP [µg/ml], BASDAI, 0-10 best-worst), physical function (BASFI, 0-10 best-worst), health status (EQ5D, 0-1 worst-best, ASAS health index [ASAS-HI], 0-17 best-worst), and fatigue (fatigue severity scale [FFS], 0-7 best-worst) were sampled at baseline and after 12 weeks. Mean and standard deviation (SD) were used for descriptive statistics. Repeated measures analysis of variance (ANOVA) was used to investigate effect of group (HG*CG) and time (PRE*POST), with a post-hoc analysis using t-tests when ANOVA indicated a significant difference in main effects or interactions. A significance level of p≤0.05 was used. Fisher´s exact test was used to study the effects over time for CRP (as dichotomized variable, > or < 4 µg/ml).

    Results

    Results presented are part of an ongoing RCT based on 19 individuals (women n=11) that have completed the 12-week follow-up analyses. The participants mean (SD) age was 48 (10) years, BMI 25 (4), VO2max 37 (6) mlO2/kg/min, and BASDAI 2.6 (0.3). No differences were present between the HG (n=9) and the CG group (n=10) at baseline for the studied variables. After 12 weeks of HIT an ANOVA interaction (p<0.05 showed that HG increased their VO2max (6.4 [3.6] mlO2/kg/min; p<0.001) but CG did not. For BMI, visceral fat area, disease activity (BASDAI), physical function (BASFI), fatigue (FFS) no differences in main effects or interactions were found (p>0.05). Health status (EQ5D) showed an ANOVA time main effect (p=0.007) where the HG increased their health status (0.10 [0.06] units; p=0.02) after 12-weeks, but CG did not. For health status measured with ASAS-HI no differences between groups were found. For dichotomized CRP-values no differences were found in either of the group’s pre-post. 

    Conclusions

    This pilot RCT shows that after 12 weeks of digital-based HIT intervention, the HG increased their aerobic capacity and EQ5D health status compared to CG, while body composition, disease activity, physical function, and fatigue did not show any significant differences between the groups. 

    References

    (1)    Sveaas SH, Bilberg a, Berg IJ, Provan SA, Rollefstad S, Semb AG, et al. high intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients. Br J Sports med. 2019

    Acknowledgement

    Thanks to participating patients, to patient partner Åsa Fiskaare and for contributions from the Swedish Rheumatism Association, Stig Thunes Foundation and Norrbacka Eugenia Foundation, Sweden

  • 19.
    Torell, Anna
    et al.
    Ängelholm Hospital, Dept. of Rehabilitation, Ängelholm, Sweden.
    Olsson, M. Charlotte
    Halmstad University, School of Business, Innovation and Sustainability.
    Andersson, Åsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Malm, Karina
    Capio Movement, Dept. of Rheumatology, Halmstad, Sweden.
    Åberg, Ida
    Capio Movement, Dept. of Rheumatology, Halmstad, Sweden.
    Wiking, Emelie
    Capio Movement, Dept. of Rheumatology, Halmstad, Sweden.
    Haglund, Emma
    Halmstad University, School of Business, Innovation and Sustainability. Lund University, Dept. of Clinical Sciences, Section of Rheumatology, Lund, Sweden; Spenshults Research and Development Centre,FoU Spenshult, Halmstad, Sweden.
    Effects of a digital-based high-intensity training intervention in individuals with axial spondyloarthritis – a randomized controlled pilot study (RCT)2023In: Annals of the Rheumatic Diseases, ISSN 0003-4967, Vol. 82, no Suppl 1, p. 1049-1049Article in journal (Refereed)
  • 20.
    Varga, Tibor V.
    et al.
    University of Copenhagen, Copenhagen, Denmark.
    Andersson, Åsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Lauruschkus, Katarina
    Lund University, Lund, Sweden.
    Tornberg, Åsa B.
    Lund University, Lund, Sweden.
    Acute and Long-Term Changes in Blood-Borne Biomarkers in Response to Dynamic Standing in Nonambulant Children With Cerebral Palsy2023In: Pediatric Exercise Science, ISSN 0899-8493, E-ISSN 1543-2920, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate acute and long-term changes in hormonal and inflammatory biomarkers in nonambulant children with cerebral palsy in response to dynamic standing exercise.

    Methods: Fourteen children with severe cerebral palsy were recruited. Anthropometrics and body composition measures were obtained. Physical activity levels before the study were assessed using hip-worn accelerometry. All children underwent a 30-minute dynamic standing exercise using the Innowalk standing aid. Respiratory data during exercise were collected using indirect calorimetry. Blood samples were collected before and after exercise. Blood samples were also obtained after two 16-week exercise protocols, in a resting state. Hormonal and inflammatory metabolites were measured from blood serum/plasma, and acute and long-term changes in biomarker levels were assessed using Wilcoxon signed-rank tests.

    Results: Of the 14 children at baseline, all had slightly/moderately/severely elevated C-reactive protein and cortisol levels. C-reactive protein levels were decreased following a 30-minute bout of dynamic standing (before exercise: 53 mg/L [interquartile range: 40-201]; after exercise: 39 mg/L [interquartile range: 20-107]; P = .04).

    Conclusions: We show that several hormonal and inflammatory biomarkers are dysregulated in children with cerebral palsy. Our preliminary results from a small, but deep-phenotyped prospective cohort indicate acute and long-term alterations of several biomarkers in response to exercise. ©2023TheAuthors.

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