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  • 1. Axelsson, S
    et al.
    Faresjö, Maria
    Hälsouniversitet i Linköping.
    Hedman, M
    Ludvigsson, J
    Casas, R
    Cryopreserved peripheral blood mononuclear cells are suitable for the assessment of immunological markers in type 1 diabetic children2008In: Cryobiology, ISSN 0011-2240, E-ISSN 1090-2392, Vol. 57, no 3, p. 201-208Article in journal (Refereed)
    Abstract [en]

    Cryopreserved peripheral blood mononuclear cells (PBMC) are commonly used when assessing immune responses in clinical trials, both for practical reasons and to minimize interassay variation, as samples are often collected and studied over time. This study investigated the effect of cryopreservation on cytokine and chemokine secretion, and on expression of regulatory T-cell associated markers, in samples from children with type 1 diabetes. PBMC were cultured before and after cryopreservation either with GAD(65) or PHA. Secretion of cytokines (IL-5, -6, -10, -12, -13 -17, IFN-gamma and TNF-alpha) and chemokines (IP-10, MCP-1, MIP-1 alpha, MIP-1 beta and RANTES) was analysed in cell supernatants using multiplex fluorochrome technique (Luminex). Expression of FOXP3 and TGF-beta mRNA was detected by multiplex real-time RT-PCR. Increased spontaneous secretion of IL-6, -10, -12, -13, IFN-gamma and MCP-1, and mRNA expression of FOXP3 and TGF-beta, was detected after cryopreservation. Stimulation with GAD65 induced higher levels of IL-6, IFN-gamma, TNF-alpha and MIP-1 alpha, whereas lower secretion was found for IL-10 and IL-13 in cryopreserved PBMC. Stimulation with PHA induced lower secretion of IP-10, MCPA and RANTES and FOXP3 mRNA expression after cryopreservation. Thus, cryopreserved PBMC were suitable to assess the immunological markers included in this study, even though their expression could differ from freshly handled cells. (C) 2008 Elsevier Inc. All rights reserved.

  • 2.
    Björkman, Berit
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Gimbler Berglund, Ingalill
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Enskär, Karin
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Division of Medical Diagnostics, Region Jönköping County, Jönköping, Sweden.
    Huus, Karina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Peri-radiographic guidelines for children with autism spectrum disorder: a nationwide survey in Sweden2017In: Child Care Health and Development, ISSN 0305-1862, E-ISSN 1365-2214, Vol. 43, no 1, p. 31-36Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to investigate the prevalence of guidelines and routines used nationwide when children with autism spectrum disorder (ASD) are taken care of and examined in a radiology department during a peri-radiographic process.

    METHOD: A nationwide survey was compiled and distributed to 94 radiology departments throughout Sweden, i.e. those performing more than 100 000 radiographic examinations annually. The survey was designed as a web questionnaire with seven questions on possible guidelines and/or routines for the departments when preparing and taking care of children with ASD in conjunction with a radiographic procedure. The data were scrutinized, using descriptive statistics.

    RESULTS: In total, 86 radiology departments responded to the survey (response rate 92%). Of those departments, 40 did not examine children with ASD. None of the departments included in the study had existing guidelines underpinning the routines when preparing and performing radiographic examinations for children diagnosed with ASD. A few departments (n = 8) would set aside more time for the procedure if it were known in advance that the child to be examined had been diagnosed with ASD. Also, some departments (n = 7) had radiographers who were more experienced in the care of children who would be appointed to perform examinations for children with ASD.

    CONCLUSION: It is suggested that guidelines should be developed in order to increase interaction in a supportive way and decrease anxiety during the peri-radiographic process with children with ASD.

  • 3.
    Björkman, Berit
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Gimbler Berglund, Ingalill
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Enskär, Karin
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Huus, Karina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Are radiographers prepared to meet children with special needs, when seen for an examination?2017In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 58, no 1 Suppl., p. 16-16Article in journal (Refereed)
    Abstract [en]

    Introduction: Anxiety is often experienced by children undergoing health care procedures, and children with autism spectrum disorders (ADS) experience more anxiety than typically developed children. A prerequisite for obtaining an optimum procedure is firstly based on the health care provider’s knowledge about children with ASD, but may also depend on the use of guidelines. Two previous national surveys showed, that none radiology or paediatric departments and a minority of anaesthesiology departments throughout Sweden use specific guidelines when seeing children with ASD. Following, the purpose was to develop guidelines to use when caring for and preparing children with ASD in those settings.

    Methods: A modified Delphi method was used, including19 experts identified from the two afore mentioned surveys. The questions considered in the process, proceeded from previous research and the results from the surveys. The experts’ responses regarding the importance of each item, were analysed and scrutinized between each round.

    Results: The Delphi process resulted in guidelines consisting of 15 items and a checklist with 16 aspects. The items cover the areas: planning and involving parents, features in the environment, use of time, communication, thehealth care professionals. The checklist covers the child’spattern of communication, anxiety, sensory stimuli, special interests and likes/dislikes.

    Conclusions: To obtain an optimum caring encounter when a child with ASD is seen in the preoperative and radiology setting, a meticulous planning is important and the environment should be adjusted for the needs of the child. To accomplish this, guidelines need to be in place and be followed.

  • 4. Bohmova, K
    et al.
    Cerny, M
    Hladikova, Z
    Vrabelova, Z
    Stadlerova, G
    Kverka, M
    Spalova, I
    Chudoba, D
    Pithova, P
    Zacharovova, K
    Brabec, R
    Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Stechova, K
    Cord blood cytokine profile detection in neonates with T1D parents: monitoring of cellular auto-reactivity using protein microarray2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 5, p. 563-571Article in journal (Refereed)
  • 5.
    Carlsson, Emma
    et al.
    Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Frostell, Anneli
    Division of Medical Diagnostics, Ryhov County Hospital, Jönköping, Sweden.
    Ludvigsson, Johnny
    Division of Paediatrics and Diabetes Research Centre, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Psychological Stress in Children May Alter the Immune Response2014In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 192, no 5, p. 2071-2081Article in journal (Refereed)
    Abstract [en]

    Psychological stress is a public health issue even in children and has been associated with a number of immunological diseases. The aim of this study was to examine the relationship between psychological stress and immune response in healthy children, with special focus on autoimmunity. In this study, psychological stress was based on a composite measure of stress in the family across the domains: 1) serious life events, 2) parenting stress, 3) lack of social support, and 4) parental worries. PBMCs, collected from 5-y-old high-stressed children (n = 26) and from 5-y-old children without high stress within the family (n = 52), from the All Babies In Southeast Sweden cohort, were stimulated with Ags (tetanus toxoid and β-lactoglobulin) and diabetes-related autoantigens (glutamic acid decarboxylase 65, insulin, heat shock protein 60, and tyrosine phosphatase). Immune markers (cytokines and chemokines), clinical parameters (C-peptide, proinsulin, glucose), and cortisol, as an indicator of stress, were analyzed. Children from families with high psychological stress showed a low spontaneous immune activity (IL-5, IL-10, IL-13, IL-17, CCL2, CCL3, and CXCL10; p < 0.01) but an increased immune response to tetanus toxoid, β-lactoglobulin, and the autoantigens glutamic acid decarboxylase 65, heat shock protein 60, and tyrosine phosphatase (IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, CCL2, CCL3, and CXCL10; p < 0.05). Children within the high-stress group showed high level of cortisol, but low level of C-peptide, compared with the control group (p < 0.05). This supports the hypothesis that psychological stress may contribute to an imbalance in the immune response but also to a pathological effect on the insulin-producing β cells.

  • 6.
    Carlsson, Emma
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Ludvigsson, J.
    Division of Paediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Huus, Karina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity2016In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 4, p. 441-450Article in journal (Refereed)
    Abstract [en]

    Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n  = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65, insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P  < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

  • 7.
    Carlsson, Emma
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Magnusson, Anette
    Tompa, Andrea
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Bülow, Per
    Gerdner, Arne
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Behavioural Science and Social Work. Jönköping University, School of Health and Welfare, HHJ. Research Platform of Social Work.
    Faresjö, Maria
    Psychological stress affects the numbers of circulating CD56+CD16+ and CD4+CD25+FoxP3+CD127- cells and induce an immune response towards type 1 diabetes-related autoantigens in young women2016Article in journal (Other academic)
  • 8.
    Carlsson, Emma
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Rundkvist, Louise
    Blomstrand, Peter
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Endurance training during adolescence induces a pro-inflammatory response directed towards the diabetes-related autoantigen tyrosine phosphatase-2Manuscript (preprint) (Other academic)
  • 9.
    Carlsson, Emma
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Rundqvist, Louise
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Blomstrand, Peter
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Enhanced immune response to a potent type 1 diabetes-related autoantigen is observed in endurance-trained boysManuscript (preprint) (Other academic)
  • 10.
    Faresjö, M
    Linköpings universitet, Hälsouniversitetet.
    Type 1 diabetes - probably a T-helper-1 associated disease, but when? Before, at or after the clinical onset of disease?2007In: Current Research in Immunolgy, Vol. 1, p. 159-170Article in journal (Other academic)
  • 11.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Children diagnosed with both type 1 diabetes and celiac disease - an Immunological challenge2016In: Immunoendocrinology, ISSN 2378-3079, Vol. 3, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) and celiac disease are both characterized by an autoimmune feature. As T1D and celiac disease share several common risk factors such as environment, genetics and immune dysregulation, patients have risk of developing the other disease subsequently. Patients with manifest T1D may have had a latent celiac disease, which is activated parallel to the anti-islet immune reactivity during the development of T1D. Contrary, a low prevalence of β-cell autoimmunity is found in young patients with celiac disease.

    The role of antigen-specific T cells and their relation to cytokines and chemokines is not well characterized in children with combination of T1D and celiac disease. Defective regulation and an impaired ability of responder T cells to be suppressed are suggested to contribute. We have previously shown that children suffering from these two immunological diseases in combination have a suppressed immune response to several antigens for example food antigens like gluten. Low percentages of both early and late effector memory CD8+ cells together with observations of immune aberrancies seen in the gut, in children who are prone to T1D, may suggests poor development of oral tolerance that may predispose for development of celiac disease.    

    This review highlights the immunological complexity in these two common pediatric immunological disorders that indicates that the combination of type 1 diabetes and celiac disease is an immunological challenge. It is obvious that we are far from understanding the immunological impact of these two autoimmune diseases in combination. This immunological challenge therefore needs to be elucidated to be able to predict and prevent these autoimmune diseases. 

  • 12.
    Faresjö, Maria
    Jönköping University, School of Health Science, HHJ. Biomedical Platform. Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine.
    Enzyme Linked Immuno-Spot; a Useful Tool in the Search for Elusive Immune Markers in Common Pediatric Immunological Diseases2012In: Cells, ISSN 2073-4409, Vol. 1, no 2, p. 141-152Article, review/survey (Refereed)
    Abstract [en]

    In order to provide better therapy we strive to increase our knowledge of how the immune system behaves and communicates in common pediatric immunological diseases, such as type 1 diabetes, allergic and celiac diseases. However, when dealing with pediatric diseases, where study subjects are almost exclusively children, blood volumes available for immunological studies are limited and as such must be carefully handled and used to their full extent. Single immune markers can easily be detected by a traditional Enzyme Linked Immunosorbent Assay (ELISA), whereas multiple markers can be detected by a fluorochrome (Luminex) or electrochemiluminescence (MSD) technique. These techniques however are sometimes not sensitive enough to detect low levels of secreted immune markers in limited sample sizes. To detect immune markers at the single-cell level, an Enzyme Linked Immuno-spot (ELISPOT) can be used to pin-point elusive immune markers in common pediatric immunological diseases.

  • 13.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    The link between psychological stress and autoimmune response in children2015In: Critical Reviews in Immunology, ISSN 1040-8401, E-ISSN 2162-6472, Vol. 35, no 2, p. 117-134Article in journal (Refereed)
    Abstract [en]

    Stress is defined as a state of threatened homeostasis or disharmony that is counteracted by a complex repertoire of physiological and behavioral adaptive responses in order to establish homeostasis. Confronted with a stressful condition, the nervous and immune systems initiate a coping process to maintain homeostasis in the body. Psychological stress, recognized as a public health issue in children and young adults, may be one mechanism to induce and maintain autoimmunity in children. It is necessary to increase our understanding of how psychological stress can affect the immune system at a young age because autoimmune diseases, especially type 1 diabetes, are alarmingly common in children. Psychological stress may be involved in other autoimmune diseases, such as celiac disease, systemic lupus erythematosus, and juvenile idiopathic arthritis, that frequently occur in children as well. This review summarizes the studies attempting to evaluate the link between psychological stress and autoimmune response in children. A number of them have observed that the autoimmune disease itself causes psychological stress. We are far from fully understanding how long-term psychological stress is linked to autoimmune response in children with a high risk of, or already diagnosed, autoimmune disease.

  • 14.
    Gimbler Berglund, Ingalill
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Björkman, Berit
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Enskär, Karin
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Huus, Karina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Management of children with Autism Spectrum Disorder in the anesthesia and radiographic context2017In: Journal of Developmental and Behavioral Pediatrics, ISSN 0196-206X, E-ISSN 1536-7312, Vol. 38, no 3, p. 187-196Article in journal (Refereed)
    Abstract [en]

    Objective: As a primary objective, this study purports to develop guidelines to better care for children with autism spectrum disorder (ASD), particularly regarding these children's preparation for anesthesia and radiologic procedures.

    Methods: Using a Delphi method with an online distribution of questionnaire, guidelines for caring for children with ASD were created. Twenty-one participants were included in the expert panel. These participants were working with children with ASD in several anesthesia and radiology departments in Sweden. A list of items was created from a previous survey and the literature. In the first round, the items with <60% agreement were discarded. Items were merged, and a new list was created. Two more similar rounds were performed. In the last 2 rounds, 21 participants responded, and 80% agreement was considered to be consensus.

    Results: The final guidelines consisted of 14 items and a checklist of 16 factors. The 5 areas covered by the items and the checklist were as follows: planning involving parents/guardians, features in the environment, and use of time, communication, and the health care professionals. The organization was important in making it possible for the health care professional to care for the individual child according to the child's needs. It was important to involve the parents/guardians to obtain knowledge about the functioning of the child.

    Conclusion: A caring encounter involving a child with ASD in the anesthesia and radiology contexts requires advance planning, catered specifically to the individual needs of each child. To accomplish this, general knowledge regarding ASD and ASD's particular manifestation in the child entrusted to their care, is required from the health care workers. The organization needs to have structures in place to facilitate this process.

  • 15.
    Gimbler Berglund, Ingalill
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Huus, Karina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Enskär, Karin
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Björkman, Berit
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. CHILD.
    Perioperative and anesthesia guidelines for children with autism: A nationwide survey from Sweden2016In: Journal of Developmental and Behavioral Pediatrics, ISSN 0196-206X, E-ISSN 1536-7312, Vol. 37, no 6, p. 457-464Article in journal (Refereed)
    Abstract [en]

    Objective: The overall aim of this study was to describe the current set of guidelines for the preparation and care for children with autism spectrum disorder (ASD) in the perioperative setting across Sweden and explore the content of these guidelines in detail.

    Method: An online questionnaire was distributed to the chairpersons of all anesthesia departments (n = 68) and pediatric departments (n = 38) throughout Sweden. Follow-up phone calls were made to those departments that did not return the questionnaire. The presence of guidelines was analyzed through descriptive statistics. These guidelines and comments on routines used in these departments were analyzed inspired by conventional content analysis.

    Results: Seven of the 68 anesthesia departments and none of the 38 pediatric departments across Sweden have guidelines for preparing and/or administering care to children with ASD within the perioperative setting. From the guidelines and routines used, 3 categories emerge: "lacking the necessary conditions," "no extra considerations needed," and "care with specific consideration for children with ASD." These 3 categories span a continuum in the care. In the first category, the anesthesia induction could result in the child with ASD being physically restrained. In the last category, the entire encounter with the health care service would be adapted to the specific needs of the child.

    Conclusion: There is a lack of evidence-based guidelines specifically designed to meet the needs of children with ASD in the preoperative period in Sweden. Further research is needed to understand if children with ASD would benefit from evidence-based guidelines.

  • 16. Hedman, M
    et al.
    Faresjö, Maria
    Hälsouniversitet i Linköping.
    Axelsson, S
    Ludvigsson, J
    Casas, R
    Impaired CD4+ and CD8+ T cell phenotype and reduced chemokine secretion in recent-onset type 1 diabetic children2008In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 153, no 3, p. 360-368Article in journal (Refereed)
  • 17. Hedman, M
    et al.
    Ludvigsson, J
    Karlsson Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Nicotinamide reduces high secretion of IFN-y in high-risk relatives even though it does not prevent type 1 diabetes2006In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 26, no 4, p. 207-213Article in journal (Refereed)
  • 18. Hjorth, Maria
    et al.
    Axelsson, Stina
    Rydén, Anna
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Ludvigsson, Johnny
    Casas, Rosaura
    GAD-alum treatment induces GAD65-specific CD4+CD25highFOXP3+ cells in type 1 diabetic patients.2011In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 138, no 1, p. 117-126Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic β-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4+CD25high cells and their association to cytokine secretion. Samples obtained 21 and 30 months after the initial injection of GAD-alum or placebo were included in the present study. GAD65-stimulation enhanced the percentage of CD4+CD25highFOXP3+ cells, but reduced the percentage of CD4+CD25+ cells, in samples from the GAD-alum treated group. Further, the GAD65-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4+CD25highFOXP3+ cells, but inversely with CD4+CD25+ cells. These new data suggest that GAD-alum treatment induced GAD65-specific T cells with regulatory features.

  • 19. Jonson, CO
    et al.
    Lernmark, Å
    Ludvigsson,
    Rutledge, EA
    Hinkkanen, A
    Faresjö, Maria
    Hälsouniversitet i Linköping.
    The importance of CTLA-4 polymorphism and human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 4, p. 185-192Article in journal (Refereed)
  • 20. Jonsson, C O
    et al.
    Phil, M
    Nyholm, C
    Cilio, M C
    Ludvigsson, J
    Faresjö, Maria
    Hälsouniversitet i Linköping.
    Regulatory T cell-associated activity in photopheresis-induced immune tolerance in reccent onset type 1 diabetes children2008In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 153, no 2, p. 174-181Article in journal (Refereed)
  • 21. Jonsson, C-O
    et al.
    Hedman, M
    Karlsson Faresjö, Maria
    Hälsouniversitet i Linköping.
    Casas, R
    Ilonen, J
    Hälsouniversitet i Linköping.
    Ludvigsson, J
    Vaarala, O
    The association of CTLA-4 and HLA class II autoimmune risk genotype with regulatory T cell marker expression in 5-year-old children2006In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 145, no 1, p. 48-55Article in journal (Refereed)
  • 22.
    Karlsson Faresjö, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Ernerudh, J
    Berlin, G
    Garcia, J
    Ludvigsson, J
    The immunological effect of photopheresis in children with newly diagnosed type 1 diabetes2005In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 58, no 3, p. 459-466Article in journal (Refereed)
  • 23.
    Karlsson Faresjö, Maria
    et al.
    Hälsouniversitet i Linköping.
    Ernerudh, J
    Ludvigsson, J
    Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes2004In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 59, no 5, p. 517-526Article in journal (Refereed)
  • 24.
    Karlsson Faresjö, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Ludvigsson, J
    Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 2, p. 173-179Article in journal (Refereed)
  • 25.
    Karlsson Faresjö, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Vaarala, O
    Thuswaldner, S
    Ilonen, J
    Hinkkanen, A
    Ludvigsson, J
    Diminished IFN-γ response to diabetes-associated autoantigens in children at diagnosis and during follow up of type 1 diabetes2006In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 22, no 6, p. 462-470Article in journal (Refereed)
  • 26.
    Karlsson, Maria
    et al.
    Hälsouniversitet i Linköping.
    Garcia, J
    Ludvigsson, J
    Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, no 9, p. 1140-1147Article in journal (Refereed)
  • 27.
    Karlsson, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Ludvigsson, J
    Determination of mRNA expression for IFN-y and IL-4 in lymphocytes from children with IDDM by RT-PCR technique1998In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 40, no 1, p. 21-30Article in journal (Refereed)
  • 28.
    Karlsson, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Ludvigsson, J
    Peptide from glutamic acid decarboxylase similar to Coxsackie B virus stimulates IFN-y mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus1998In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 35, no 3, p. 137-144Article in journal (Refereed)
  • 29.
    Karlsson, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Ludvigsson, J
    The ABBOS-peptide from bovine serum albumin causes an IFN-y and IL-4 mRNA respose in lymphocytes from children with recent onset of type 1 diabetes2000In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 47, no 3, p. 199-207Article in journal (Refereed)
  • 30.
    Karlsson, Maria
    et al.
    Hälsouniversitetet i Linköping.
    Sederholm Lawesson, S
    Ludvigsson, J
    Th1-like dominance in high-risk first-degree relatives of Type I diabetic patients2000In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 43, no 6, p. 742-749Article in journal (Refereed)
  • 31. Kivling, A
    et al.
    Nilsson, L
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    How and when to pick up the best signals from markers associated with T-regulatory cells?2009In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 345, no 1-2, p. 29-39Article in journal (Refereed)
  • 32. Kivling, A
    et al.
    Nilsson, L
    Fälth-Magnusson, K
    Söllvander, S
    Johansson, C
    Faresjö, Maria
    Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Biomedical Platform.
    Diverse FOXP3 expression in children with type 1 diabetes and celiac disease2008In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1150, p. 273-277Article in journal (Refereed)
  • 33. Ludvigsson, J
    et al.
    Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Hedman, M
    Axelsson, S
    Chéramy, M
    Phil, M
    Vaarala, O
    Forsander, G
    Ivarsson, S
    Johansson, C
    Lindh, A
    Nilsson, N-Ö
    Åman, J
    Örtqvist, E
    Zerhouni, P
    Casas, R
    GAD treatment and insulin secretion in recent-onset type 1 diabetes2008In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 359, no 18, p. 1909-1920Article in journal (Refereed)
  • 34. Michalek, J
    et al.
    Vrabelova, Z
    Hrotekova, Z
    Kyr, M
    Pejchlova, M
    Kolouskova, S
    Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Stechova, K
    Hälsouniversitetet i Linköping.
    Immune regulatory T cells in siblings of children suffering from type 1 diabetes mellitus2006In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 64, no 5, p. 531-535Article in journal (Refereed)
  • 35. Nilsson, L
    et al.
    Kivling, A
    Jalmelid, M
    Fälth-Magnusson, K
    Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Combinations of common chronic paediatric diseases deviate the immune response in diverging directions2006In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 146, no 3, p. 433-442Article in journal (Refereed)
  • 36.
    Rundqvist, Louise
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Engvall, Jan
    Department of Clinical Physiology, Linköping University, Linköping, Sweden.
    Blomstrand, Peter
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Carlsson, Emma
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Resting level of insulin-like growth factor 1 is not at play in cardiac enlargement in endurance-trained adolescentsManuscript (preprint) (Other academic)
  • 37.
    Rundqvist, Louise
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Engvall, Jan
    Department of Clinical Physiology, Linköping University, Linköping, Sweden.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. The Academy of Health and Care, Region Jönköping County, Jönköping, Sweden.
    Blomstrand, Peter
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Left ventricular diastolic function is enhanced after peak exercise in endurance-trained adolescents as well as in their non-trained controls2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 6, p. 1054-1061Article in journal (Refereed)
    Abstract [en]

    The aims of the study were to explore the temporal change of cardiac function after peak exercise in adolescents, and to investigate how these functional changes relate to maximal oxygen uptake (VO2max ). The cohort consisted of 27 endurance-trained adolescents aged 13-19 years, and 27 controls individually matched by age and gender. Standard echocardiography and colour tissue Doppler were performed at rest, and immediately after as well as 15 min after a maximal cardio pulmonary exercise test (CPET) on a treadmill. The changes in systolic and diastolic parameters after exercise compared to baseline were similar in both groups. The septal E/e'-ratio increased immediately after exercise in both the active and the control groups (from 9·2 to 11·0; P<0·001, and from 8·7 to 10·2; P = 0·008, respectively). In a comparison between the two groups after CPET, the septal E/e'-ratio was higher in the active group both immediately after exercise and 15 min later compared to the control group (P = 0·007 and P = 0·006, respectively). We demonstrated a positive correlation between VO2max and cardiac function including LVEF and E/e' immediately after CPET, but the strongest correlation was found between VO2max and LVEDV (r = 0·67, P<0·001) as well as septal E/e' (r = 0·34, P = 0·013). Enhanced diastolic function was found in both groups, but this was more pronounced in active adolescents. The cardiac functional response to exercise, in terms of LVEF and E/e', correlates with the increase in VO2 uptake. These findings in trained as well as un-trained teenagers have practical implications when assessing cardiac function.

  • 38.
    Rundqvist, Louise
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Engvall, Jan
    Department of Clinical Physiology, Department of Medical and Health Sciences, Linköping University, Linköping.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Carlsson, Emma
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Blomstrand, Peter
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Regular endurance training in adolescents impacts atrial and ventricular size and function2017In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 18, no 6, p. 681-687Article in journal (Refereed)
    Abstract [en]

    Aims: The aims of the study were to explore the effects of long-term endurance exercise on atrial and ventricular size and function in adolescents and to examine whether these changes are related to maximal oxygen uptake (VO2max).

    Methods and results: Twenty-seven long-term endurance-trained adolescents aged 13–19 years were individually matched by age and gender with 27 controls. All participants, 22 girls and 32 boys, underwent an echocardiographic examination at rest, including standard and colour tissue Doppler investigation. VO2max was assessed during treadmill exercise. All heart dimensions indexed for body size were larger in the physically active group compared with controls: left ventricular end-diastolic volume 60 vs. 50 mL/m2 (P <0.001), left atrial volume 27 vs. 19 mL/m2 (P <0.001), and right ventricular (RV) and right atrial area 15 vs. 13 and 9 vs. 7 cm2/m2, respectively (P <0.001 for both). There were strong associations between the size of the cardiac chambers and VO2max. Further, we found improved systolic function in the active group compared with controls: left ventricular ejection fraction 61 vs. 59% (P= 0.036), tricuspid annular plane systolic excursion 12 vs. 10 mm/m2 (P= 0.008), and RV early peak systolic velocity s′ 11 vs. 10 cm/s (P = 0.031).

    Conclusion: Cardiac remodelling to long-term endurance exercise in adolescents is manifested by an increase in atrial as well as ventricular dimensions. The physically active group also demonstrated functional remodelling with an increase in TAPSE and systolic RV wall velocity. These findings have practical implications when assessing cardiac enlargement and function in physically active youngsters.

  • 39. Rydén, A
    et al.
    Bolmeson, C
    Jonsson, C-O
    Cilio, CM
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children2012In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 28, p. 84-96Article in journal (Refereed)
    Abstract [en]

    Background: High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease. 

    Methods: T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the disease. Isolated peripheral blood mononuclear cells were stimulated with the T1D-associated glutamic acid decarboxylase 65 and phytohaemagglutinin. Subsequently, soluble CTLA-4, full-length CTLA-4, FOXP3 and TGF-beta mRNA transcription were quantified and protein concentrations of soluble CTLA-4 were measured in culture supernatant and sera.

    Results and Conclusions: Low protein concentrations of circulating soluble CTLA-4 and a positive correlation between soluble CTLA-4 mRNA and protein were seen in T1D, in parallel with a negative correlation in healthy subjects. Further, low levels of mitogen-induced soluble CTLA-4 were accompanied by low C-peptide levels. Interestingly, low mitogen-induced soluble CTLA-4 mRNA and low TGF-beta mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down-regulating immune mechanisms during the pre-diabetic phase. 

  • 40. Rydén, A
    et al.
    Stechova, K
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes2009In: Diabetes Metabolism Reviews, ISSN 0742-4221, E-ISSN 1099-0895, Vol. 25, no 4, p. 335-343Article in journal (Refereed)
    Abstract [en]

    Background: Type 1 diabetes (T1D) is all autoimmune disease dominated by loss of self-tolerance resulting in depletion of the beta-cells. This Study aims to confirm previous observations of a dominant T-helper (Th)1-like profile during the period close to onset of disease. Further, to follow the immune response from onset to 2 years duration, the Study focused on spontaneous as well as autoantigen-induced immune profile. 

    Methods: Peripheral blood mononuclear cells were collected 4 days and 1 and 2 years after diagnosis of T1D children, from healthy children carrying the human leukocyte antigen-risk genes and from high-risk children (ICA >= 20 IJDF units). Peripheral blood mononuclear cells were stimulated with glutamic acid decarboxylase (GAD(65)) and phytohaemagglutinin (PHA). Cytokines and chemokines were detected in cell-culture supernatants by protein microarray (naive T-cells; interleukin (IL)-7, Th1; interferon-gamma, turnout necrosis factor-beta, Th2; IL-5, Th3; transforming growth factor-beta, T-regulatory cell type 1; IL-10 and inflammatory cytokines; tumour necrosis factor-alpha, IL-6 and chemokines; monocyte chemoattractant protein-1, monokine upregulated by IFN-gamma) in relation to clinical outcome (C-peptide). 

    Results: High-risk children showed a dominant Th1-associated profile with high spontaneous and GAD(65)-induced secretion. The mitogen PHA instead induced a Th2-associated response exclusively in high-risk children. In contrast, newly diagnosed T1D children showed a pronounced Th3-associated cytokine profile as well as a burst of inflammatory cytokines and chemokines secreted both spontaneously and by GAD(65) and PHA stimulation. The immune response to GAD(65) and PHA, however, diminished with duration of disease. 

    Conclusion: A dominant Thl-associated immune profile was observed during the pre-diabetic phase. This Th1 dominance, however, diminished in favour of a temporary increase in a Th3-associated and inflammatory immune profile at the onset of disease. 

  • 41.
    Rydén, Anna
    et al.
    Division of Paediatrics & Diabetes Research Centre, Department of Clinical & Experimental Medicine, Faculty of Health Sciences, Linköping University.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Altered immune profile from pre-diabetes to manifestation of type 1 diabetes2013In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 100, no 1, p. 74-84Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:While the mechanisms leading to β-cell destruction and clinical onset of T1D are still unclear, the composition of the immune profile is probably important for the outcome of immune activity. The aim of this study was to investigate the composition and possible changes of the immunological profile, spontaneously and following stimulation with the autoantigens GAD65, and HSP60, at high-risk and T1D onset and further to 8 months post diagnosis.

    METHODS:Fifteen first-degree relatives of T1D patients with a high risk of developing the disease within five years, 25 children approximately four days and 8 months after diagnosis of T1D and 16 healthy children were included in the study. Cytokines (IL-1β, -6, -7, -10, -13, -17, IFN-γ and TNF-α) and chemokines (CCL2, -3, -4, -5 and CXCL10) associated with Th1, Th2, Tr1 and inflammatory cells were detected in cell culture supernatants by Luminex-technique, and markers associated with regulatory T-cells (FOXP3, CTLA-4 and TGF-β) by real-time RT-PCR.

    RESULTS:High-risk individuals differed in immunity from that seen in healthy and T1D children. High-risk individuals had a low TNF-α response and fewer responders from mitogen exposure as well as low spontaneous secretions of IL-13 compared to healthy children. High-risk individuals that later developed T1D, had a lower FOXP3 and CTLA-4 mRNA expression, following stimulation with GAD65, in combination with higher secretion of the pro-inflammatory chemokine CCL4.

    CONCLUSION:Changes in immunity seen in individuals with high risk of developing T1D points to alterations/actions in the immune system already early in the pre-diabetic phase.

  • 42.
    Rydén, Anna
    et al.
    Linköping University.
    Faresjö, Maria
    Jönköping University, School of Health Science, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health Science, HHJ. Biomedical Platform.
    Efficient expansion of cryopreserved CD4+ CD25+CD127lo/-cells in Type 1 diabetes2011In: Results in Immunology, ISSN 2211-2839, Vol. 1, no 1, p. 36-44Article in journal (Refereed)
    Abstract [en]

    Increased attention has been drawn to the important role played by regulatory T-cells (Treg) in immune homoeostasis. However, the small numbers of Tregs make them elusive to study. We investigated the cryostability of Tregs and whether they can be expanded from cryopreserved peripheral blood mononuclear cells (PBMCs). Further, to elucidate if there is a difference in ex-vivo frequency or in vitro expansion of Tregs among T1D children (n=9), high-risk (n=7) and healthy (n=10) individuals, Tregs defined as CD4+CD25+CD127lo/− were isolated from cryopreserved PBMCs.

    Cryopreserved PBMCs maintained a stable expression of Treg-markers. Tregs were efficiently expanded in vitro from all donors and Tregs from T1D children acquired higher FOXP3 expression compared to healthy subjects. T1D children had a significantly lower percentage of Tregs among CD4+ T-cells and also lower Treg to CD4+CD25 cell ratios compared to healthy individuals.

  • 43.
    Rydén, Anna
    et al.
    Division of Paediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Ludvigsson, Johnny
    Division of Paediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Fredriksson, Mats
    Linköping Academic Research Center, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    General immune dampening is associated with disturbed metabolism at diagnosis of type 1 diabetes2014In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 75, no 1, p. 45-50Article in journal (Refereed)
    Abstract [en]

    Background:

    Type 1 diabetes (T1D) is a serious diagnosis with the prospect of grave short- and long-term complications and even death if poorly managed. An attempt has been made to describe how clinical and immunological deviations might influence each other close to the diagnosis of T1D.

    Methods:

    Sixty-nine newly diagnosed T1D children were studied together with a reference group of 30 healthy children. Cytokines (interleukin (IL)-6, IL-10, IL-13, IL-17, interferon-γ, and tumor necrosis factor-α) were detected in in vitro culture by multiplex fluorochrome technique. Information of clinical status of the patients such as BMI, weight loss, pubertal stage, duration of symptoms, previous and/or ongoing infections, insulin requirement, and ketoacidosis were gathered together with the analysis of C-peptide and glycosylated hemoglobin (HbA1c).

    Results:

    In general, low cytokine secretion was found at diagnosis of T1D. However, high C-peptide, short duration of symptoms, or an infection prior to diagnosis was associated with increased immune activity including proinflammatory, Th2-associated, and Tr1-associated cytokines. In contrast, ketoacidosis and later pubertal stage at onset of disease were more related to a Th1-prone response.

    Conclusion:

    There is a general immune dampening at diagnosis of T1D, which appears to be related to the metabolic state close to diagnosis.

  • 44. Schloot, N C
    et al.
    Meierhoff, G
    Karlsson Faresjö, Maria
    Hälsouniversitet i Linköping.
    Ott, P
    Putnam, A
    Lehman, P
    Gottlieb, P
    Roep, B O
    Peakman, M
    Tree, T
    Comparison of cytokine ELISpot assay formats for the detection of islet antigen autoreactive T cells: Report of the third immunology of diabetes society T-cell workshop2003In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 21, no 4, p. 365-376Article in journal (Refereed)
  • 45. Sirsjö, A
    et al.
    Karlsson, Maria
    Hälsouniversitetet i Linköping.
    Gidlöf, A
    Rollman, A
    Törmä, H
    Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes1996In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 134, no 4, p. 643-648Article in journal (Refereed)
  • 46. Stechova, K
    et al.
    Bohmova, K
    Vrabelova, Z
    Sepa, A
    Stadlerova, G
    Zacharovova, K
    Faresjö, Maria
    Hälsouniversitet i Linköping.
    High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes2007In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 23, no 6, p. 462-471Article in journal (Refereed)
  • 47. Stechova, K
    et al.
    Halbhuber, Z
    Hubackova, M
    Kayserova, J
    Petruzelkova, L
    Vcelakova, J
    Kolouskova, S
    Ulmannova, T
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Neuwirth, A
    Spisek, R
    Sediva, A
    Filipp, D
    Sumnik, Z
    Case report: type 1 diabetes in monozygotic quadruplets2012In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 20, no 4, p. 457-462Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-α further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called ‘fertile-field’ hypothesis proposing that genetic predisposition to anti-islet autoimmunity is ‘fertilized’ and precipitated by a viral infection leading to a fully blown T1D.

  • 48. Stechova, K
    et al.
    Kolouskova, S
    Sumnik, Z
    Cinek, O
    Karlsson Faresjö, Maria
    Hälsouniversitetet i Linköping.
    Chudoba, D
    Dovolilova, E
    Vrabelova, Z
    Saudek,
    Vavrenic, J
    Anti-GAD65 reactive peripheral blood mononuclear cells in the pathogenesis of cystic fibrosis relatied diabetes mellitus2005In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 38, no 4, p. 319-323Article in journal (Refereed)
  • 49. Stechova, K
    et al.
    Spalovat, I
    Durilova, M
    Baratskovat, M
    Cernys, M
    Cerena, M
    Pithova, D
    Chudoba, D
    Ullmanova, T
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Influence of maternal hyperglycaemia on cord blood mononuclear cells in response to diabetes-associated autoantigens2009In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 70, p. 149-158Article in journal (Refereed)
    Abstract [en]

    Perfect maternal diabetes compensation is crucial for the outcome of the baby. However, little is known how hyperglycaemia influences the specific immune response. Furthermore, babies of type 1 diabetes (T1D) mothers have less risk of development T1D than babies with a T1D father. This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes-associated autoantigens. Populations: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (= 15) or acceptable (= 25) compensation. (2) newborns with T1D father (= 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (= 10) (4) control newborns (= 25). Spontaneous as well as diabetes-associated autoantigen-stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cytokine and chemokine spectra. A prominent Th1 response (high IFN-gamma) from autoantigen stimulation was observed especially in babies of T1D fathers (= 0.001) and also in mothers with perfect diabetes compensation during the 3rd trimester (= 0.016) in comparison with control newborns. By contrast, cord blood mononuclear cells cultivated in vitro in high glucose concentration decreased the diabetogenic stimulated Th1 cytokine response. Maternal ‘sweet’ as well as ‘autoimmune environment’ may both lead to lower occurrence of T1D within their offspring. Further studies will reveal the exact immunological mechanism of this observation.

  • 50.
    Tompa, Andrea
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform. Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden.
    Nilsson-Bowers, Anette
    Department of Laboratory Medicine, Region Jönköping County, Jönköping, Sweden.
    Faresjö, Maria
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine. Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Subsets of CD4+, CD8+, and CD25hi Lymphocytes Are in General Not Influenced by Isolation and Long-Term Cryopreservation2018In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 201, no 6, p. 1799-1809Article in journal (Refereed)
    Abstract [en]

    Several key factors can affect the outcome of immunological studies; isolation/cryopreservation can possibly alter T, B, NK, and T-regulatory (Treg) cell marker expression patterns. Blood samples from 50 blood donors supplemented with Na-heparin or K2EDTA were handled within 4 and 24 h after blood sampling. PBMC were isolated with different density gradients. Flow cytometric analysis of intracellular and extracellular CD markers was performed on blood samples freshly isolated PBMC, and PBMC was thawed 6 and 12 mo post-cryopreservation for the purpose of identifying B, NK, Th, T-cytotoxic, and Treg cells. No differences were observed in the percentages for CD3+, CD3+CD4+, CD3+CD8+, CD19+, or CD56+CD16+ cells within 24 h of sampling regardless of which supplement or isolation techniques were used. Differentiated (diff) CD4+ cells were in general less affected by isolation and cryopreservation than diff CD8+ cells. Terminally diff effector CD4+ and CD8+ cells were not affected by either isolation of lymphocytes or cryopreservation. In contrast, naive and early-diff effector memory CD4+ and CD8+ cells were affected by isolation and cryopreservation. The percentages of Treg cells defined as CD4+CD25hi expressing CD101 or CD129, CD4+CD25hiCD127, and CD4+CD25hiCD127FOXP3+, respectively, remained stable after isolation and cryopreservation. Subsets expressing CD127, with or without FOXP3, were not affected by isolation/cryopreservation. Subsets expressing CD39, contrary to CD45RA, on CD4+CD25+CD127 cells with or without FOXP3 were not affected by either isolation or cryopreservation. In conclusion, subsets of CD4+, CD8+, and CD25hi lymphocytes are in general not influenced by isolation and long-term cryopreservation.

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