| 1. |
- Chéramy, Mikael, et al.
(författare)
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GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD(65) enzyme activity and humoral response
- 2010
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Ingår i: Clinical Immunology. - : Elsevier Science B.V., Amsterdam. - 1521-6616 .- 1521-7035. ; 137:1, s. 31-40
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that two injections of 20 mu g GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pretreatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response.
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| 2. |
- Gray, Penelope, et al.
(författare)
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Seroepidemiological assessment of the spread of SARS-CoV-2 among 25 and 28 year-old adult women in Finland between March 2020-June 2022
- 2024
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7 July
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Serological surveys of the prevalence of SARS-CoV-2 are instrumental to understanding the course of the COVID-19 epidemic. We evaluate the seroprevalence of SARS-CoV-2 among young adult Finnish females residing in 25 communities all over Finland from 2020 until 2022. Methods Between 1st March 2020 and 30th June 2022, 3589 blood samples were collected from 3583 women born in 1992–95 when aged 25 or 28 years old attending the follow-up of an ongoing population-based trial of cervical screening strategies. The crude and population standardized SARS-CoV-2 seroprevalence was measured using nucleocapsid (induced by infection) and spike wild-type (WT) protein (induced both by infection and by vaccination) antigens over time and stratified by place of residence (inside or outside the Helsinki metropolitan region). Results During 2020 (before vaccinations), spike-WT and nucleocapsid IgG antibodies followed each other closely, at very low levels (<5%). Spike-WT seropositivity increased rapidly concomitant with mass vaccinations in 2021 and reached 96.3% in the 2nd quartile of 2022. Antibodies to nucleocapsid IgG remained relatively infrequent throughput 2020–2021, increasing rapidly in the 1st and 2nd quartiles of 2022 (to 19.7% and 56.6% respectively). The nucleocapsid IgG seropositivity increased more profoundly in participants residing in the Helsinki metropolitan region (4.5%, 8.4% and 43.9% in 2020, 2021 and 2022 respectively) compared to those residing in communities outside the capital region (4.5%, 4.3% and 34.7%). Conclusions Low SARS-CoV-2 infection-related seroprevalence during 2020–2021 suggest a comparatively successful infection control. Antibodies to the SARS-CoV-2 WT spike protein became extremely common among young women by the end of 2021, in line with the high uptake of SARS-CoV-2 vaccination. Finally, the rapid increase of seroprevalences to the SARS-CoV-2 nucleocapsid protein during the first and second quartile of 2022, imply a high incidence of infections with SARS-CoV-2 variants able to escape vaccine-induced protection.
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| 3. |
- Hallen, Thomas, et al.
(författare)
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Genome-Wide DNA Methylation Differences in Nonfunctioning Pituitary Adenomas With and Without Postsurgical Progression
- 2022
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:8, s. 2318-2328
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Tidskriftsartikel (refereegranskat)abstract
- Context Tumor progression in surgically treated patients with nonfunctioning pituitary adenomas (NFPAs) is associated with excess mortality. Reliable biomarkers allowing early identification of tumor progression are missing. Objective To explore DNA methylation patterns associated with tumor progression in NFPA patients. Methods This case-controlled exploratory trial at a university hospital studied patients who underwent surgery for NFPA that had immunohistochemical characteristics of a gonadotropinoma. Cases included patients requiring reintervention due to tumor progression (reintervention group, n = 26) and controls who had a postoperative residual tumor without tumor progression for at least 5 years (radiologically stable group, n = 17). Genome-wide methylation data from each tumor sample were analyzed using the Infinium MethylationEPIC BeadChip platform. Results The analysis showed that 605 CpG positions were significantly differently methylated (differently methylated positions, DMPs) between the patient groups (false discovery rate adjusted P value < 0.05, beta value > 0.2), mapping to 389 genes. The largest number of DMPs were detected in the genes NUP93 and LGALS1. The 3 hypomethylated DMPs and the 3 hypermethylated DMPs with the lowest P values were all significantly (P < 0.05) and individually associated with reintervention-free survival. One of the hypermethylated DMPs with the lowest P value was located in the gene GABRA1. Conclusion In this exploratory study, DNA methylation patterns in NFPA patients were associated with postoperative tumor progression requiring reintervention. The DMPs included genes that have been previously associated with tumor development. Our study is a step toward finding epigenetic signatures to predict tumor progression in patients with NFPA.
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| 4. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 5. |
- Josephson, Henrik, et al.
(författare)
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Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells
- 2020
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Ingår i: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria play crucial roles in cellular metabolism, signaling, longevity, and immune defense. Recent evidences have revealed that the host microbiota, including bacterial pathogens, impact mitochondrial behaviors and activities in the host. The pathogenicity of Pseudomonas aeruginosa requires quorum sensing (QS) cell-cell communication allowing the bacteria to sense population density and collectively control biofilm development, virulence traits, adaptation and interactions with the host. QS molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C-12-HSL), can also modulate the behavior of host cells, e.g., epithelial barrier properties and innate immune responses. Here, in two types of cells, fibroblasts and intestinal epithelial cells, we investigated whether and how P. aeruginosa 3O-C-12-HSL impacts the morphology of mitochondrial networks and their energetic characteristics, using high-resolution transmission electron microscopy, fluorescence live-cell imaging, assay for mitochondrial bioenergetics, and quantitative mass spectrometry for mitoproteomics and bioinformatics. We found that 3O-C-12-HSL induced fragmentation of mitochondria, disruption of cristae and inner membrane ultrastructure, altered major characteristics of respiration and energetics, and decreased mitochondrial membrane potential, and that there are distinct cell-type specific details of these effects. Moreover, this was mechanistically accompanied by differential expression of both common and cell-type specific arrays of components in the mitochondrial proteome involved in their structural organization, electron transport chain complexes and response to stress. We suggest that this effect of 3O-C-12-HSL on mitochondria may represent one of the events in the interaction between P. aeruginosa and host mitochondria and may have an impact on the pathogens strategy to hijack host cell activities to support their own survival and spreading.
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| 6. |
- Kurz, Tino, et al.
(författare)
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A myelopoiesis gene signature during remission in ANCA associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy
- 2014
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Ingår i: Clinical and Experimental Immunology. - : Wiley-Blackwell. - 0009-9104 .- 1365-2249. ; 175:2, s. 215-226
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Tidskriftsartikel (refereegranskat)abstract
- A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti-neutrophil cytoplasm antibody associated vasculitis (AAV) and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors (CEBPA, CEBPB, SPIB, SPI1) and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were analyzed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMCs, PMNs) and MPO (PBMCs). PR3 and SPIB mRNA correlated positively in control but negatively in patient PBMCs. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses but correlated to steroid treatment. Prednisolone doses were negatively linked to SPIB and miR-155-5p, miR-339-5p (PBMCs) and to miR-221, miR-361, miR-505 (PMNs). PR3 mRNA in PBMCs correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multifactorial, but to an important part explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.
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| 7. |
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| 8. |
- Pushpamithran, Giggil, et al.
(författare)
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No impact of helminth coinfection in patients with smear positive tuberculosis on immunoglobulin levels using a novel method measuring Mycobacterium tuberculosis-specific antibodies
- 2023
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Ingår i: Allergy, Asthma and Clinical Immunology. - : BMC. - 1710-1484 .- 1710-1492. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Helminth/tuberculosis (TB)-coinfection can reduce cell-mediated immunity against Mycobacterium tuberculosis (Mtb) and increase disease severity, although the effects are highly helminth species dependent. Mtb have long been ranked as the number one single infectious agent claiming the most lives. The only licensed vaccine for TB (BCG) offers highly variable protection against TB, and almost no protection against transmission of Mtb. In recent few years the identification of naturally occurring antibodies in humans that are protective during Mtb infection has reignited the interest in adaptive humoral immunity against TB and its possible implementation in novel TB vaccine design. The effects of helminth/TB coinfection on the humoral response against Mtb during active pulmonary TB are however still unclear, and specifically the effect by globally prevalent helminth species such as Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, Trichuris trichiura. Plasma samples from smear positive TB patients were used to measure both total and Mtb-specific antibody responses in a Peruvian endemic setting where these helminths are dominating. Mtb-specific antibodies were detected by a novel approach coating ELISA-plates with a Mtb cell-membrane fraction (CDC1551) that contains a broad range of Mtb surface proteins. Compared to controls without helminths or TB, helminth/TB coinfected patients had high levels of Mtb-specific IgG (including an IgG1 and IgG2 subclass response) and IgM, which were similarly increased in TB patients without helminth infection. These data, indicate that helminth/TB coinfected have a sustained humoral response against Mtb at the level of active TB only. More studies on the species-specific impact of helminths on the adaptive humoral response against Mtb using a larger sample size, and in relation to TB disease severity, are needed.
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| 9. |
- Samuelsson, Marcus, 1967-, et al.
(författare)
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Ett observationsprotokoll för att studera ledarskap för lärande
- 2021
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Ingår i: Venue. - Linköping : Linköping University Electronic Press. - 2001-788X. ; :19
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Ett sätt att få syn på hur lärare leder undervisning är att använda sig av observationer och då kan ett observationsprotokoll vara till hjälp. Hur ett protokoll togs fram och hur det till slut ser ut beskrivs i denna artikel.
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| 10. |
- Samuelsson, Marcus, 1967-, et al.
(författare)
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Ett observationsprotokoll för att studera ledarskap för lärande
- 2022
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Ingår i: Ledarskap för lärande. - Linköping : Linköping University Electronic Press. - 9789179292881 ; , s. 27-35
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Denna artikel beskriver en process och en produkt som tagits fram inom ramen för ett ULF-projekt (Thorsten, 2021), ett forskningsprojekt kallat Ledarskap för lärande. Namnet och inriktningen speglar ett intresse från skolledare och lärare i tre kommuner, Mjölby, Norrköping och Söderkö- ping. I dessa kommuner fanns ett behov av att öka kunskapen om ledarskap i relation till lärande vilket gjorde att ett praktiknära forskningsprojekt tillsammans med två forskare från Linköpings universitet påbörjades. Från varje kommun rekryterades medforskande lärare (två från Mjölby, fyra från Norrköping och två från Söderköping) som skulle delta i forskningsgruppen.I forskningsprojektets inledning bestämdes att vi, som ett sätt att påverka lärares sätt att leda under- visning, skulle utforma en intervention i form av en fortbildning för lärare. Till följd av det be- stämdes också att interventionen skulle föregås och följas upp av observationer av lärarna som skulle delta i interventionen. Dessa observationer skulle genomföras av de medforskande lärarna. Till stöd för deras observationer behövdes ett observationsprotokoll. Syftet med protokollet var att identifiera kvalitativa skillnader i lärares sätt att leda undervisning.Vi påbörjade arbetet med att diskutera kring vad observationer innebär och utgick då från en text av Granström (2004) som handlar om att göra tillförlitliga observationer och om vilken roll obser- vatören kan inta i relation till dem/de som observeras. Vi började också resonera om tänkbara svar på två grundläggande frågor om observation som Arno Bellack (1978) formulerat Vilka dimens- ioner av klassrumsbeteenden ska observeras? och Hur ska observationerna utföras? Dessa frågor kom att följa oss under hela processen och svaret på dem fann vi på flera sätt. Hur observations- protokollet kom att se ut påverkades av flera faktorer: (a) den erfarenhetsbaserade kunskapen i forskargruppen, (b) andra observationsprotokoll, (c) tidigare forskning och (d) utprovning av protokollet. Dessa fyra delar sammanvävdes på olika sätt under olika delar av processen.
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| 11. |
- Sandstedt, Mårten, et al.
(författare)
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Complete fatty degeneration of thymus associates with male sex, obesity and loss of circulating naïve CD8+ T cells in a Swedish middle-aged population
- 2023
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Ingår i: Immunity & Ageing. - : BMC. - 1742-4933. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Fatty degeneration of thymus (or thymus involution) has long been considered a normal ageing process. However, there is emerging evidence that thymic involution is linked to T cell aging, chronic inflammation and increased morbidity. Other factors, aside from chronological age, have been proposed to affect the involution rate. In the present study, we investigated the imaging characteristics of thymus on computed tomography (CT) in a Swedish middle-aged population. The major aims were to establish the prevalence of fatty degeneration of thymus and to determine its associations with demographic, lifestyle and clinical factors, as well as inflammation, T cell differentiation and thymic output. Results In total, 1 048 randomly invited individuals (aged 50-64 years, 49% females) were included and thoroughly characterized. CT evaluation of thymus included measurements of attenuation, size and a 4-point scoring system, with scale 0-3 based on the ratio of fat and soft tissue. A majority, 615 (59%) showed complete fatty degeneration, 259 (25%) predominantly fatty attenuation, 105 (10%) half fatty and half soft-tissue attenuation, while 69 (6.6%) presented with a solid thymic gland with predominantly soft-tissue attenuation. Age, male sex, high BMI, abdominal obesity and low dietary intake of fiber were independently associated with complete fatty degeneration of thymus. Also, fatty degeneration of thymus as well as low CT attenuation values were independently related to lower proportion of naive CD8(+) T cells, which in turn was related to lower thymic output, assessed by T- cell receptor excision circle (TREC) levels. Conclusion Among Swedish middle-aged subjects, nearly two-thirds showed complete fatty degeneration of thymus on CT. This was linked to depletion of naive CD8(+) T cells indicating that CT scans of thymus might be used to estimate immunological aging. Furthermore, our findings support the intriguing concept that obesity as well as low fiber intake contribute to immunological aging, thereby raising the possibility of preventive strategies.
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| 12. |
- Skoglund Andersson, Camilla
(författare)
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Low density lipoprotein (LDL) heterogeneity : implications for cardiovascular disease and genetic influence
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The low density lipoprotein (LDL) particle population is heterogeneous with regard to several structural and functional properties that may influence its atherogenic potential. A preponderance of small, dense LDL is associated with an increased risk of coronary heart disease (CHD), and also predicts future CHD events. However, the metabolic pathways for the formation of the small, dense LDL are not yet fully understood. There is strong evidence that the LDL particle size distribution is under genetic influence, although the major regulating genes remain unknown. The present studies were conducted to further elucidate the role of LDL heterogeneity in cardiovascular disease, and to evaluate the metabolic arid genetic determinants of LDL particle size distribution. In study I the influence of LDL particle size distribution on intima-media thickness (IMT) of the common carotid artery (CCA) was investigated in healthy 50-year-old men. A high-resolution non-denaturing polyacrylamide gradient (3-7.5%) gel electrophoresis (GGE) procedure was developed to measure LDL peak particle size (run), relative distribution (%) and plasma concentration (mg/L) of four LDL subfractions. The IMT of the CCA was measured by B-mode ultrasound. The results of this study show that the plasma concentration of small, dense LDL (LDL-III) is a strong and independent indicator of early atherosclerosis in healthy, middle-aged men. In study II the effects of artificial and exhaustive lipolysis on potentially atherogenic properties of LDL were investigated in healthy normotriglyceridaemic men. After in vitro and in vivo lipolysis of serum and plasma triglycerides, respectively, the LDL particle population was characterised with regard to size, composition, and susceptibility to oxidative modification The results of this study demonstrate that an exaggerated or efficient lipolysis of plasma triglycerides results in the generation of new LDL particles with an increased content of alpha-tocopherol and increased resistance to oxidative modification. In studies III-V the influence of common functional variants in candidate genes (encoding proteins or enzymes with important roles in lipoprotein metabolism) on LDL heterogeneity was investigated. In study III, polymorphisms in the cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (HL), and apolipoprotein E (apoE) genes were studied in relation to LDL particle size in 377 healthy, middle-aged men The results of this study show that the investigated polymorphisms are associated with moderate effects on the LDL particle size, consistent with respect to protein function and proposed association with CHD risk. In study IV, the isolated and combined effects of the apolipoprotein. B (apoB) and the apoE polymorphisms on LDL particle size and risk of CHD were investigated in 405 survivors of a first myocardial infarction before the age of 60, and 769 healthy individuals. The results of this study demonstrate that a gene-gene interaction between the apoB and apoE polymorphisms is associated with a markedly elevated concentration of small, dense LDL, which is further conveyed to an increased risk of myocardial infarction. In study V, the influence of a common variant in the MTP gene promoter on the secretion pattern of apoB-containing lipoproteins and plasma LDL heterogeneity was investigate& A total of 12 healthy men were recruited by genotype to participate in apoB stable isotope turnover studies, and kinetic parameters were calculated by multi-compartmental modelling. LDL particle size was measured in 377 healthy, middle-aged men The results of this study show that the MT? promoter polymorphism is associated with a reduced direct production of IDL+LDL particles, which appears to be directly related to lower plasma concentrations of large LDL particles. Conclusions: The studies presented here demonstrate that the atherogenic properties of plasma LDL goes far beyond the routinely measured LDL cholesterol concentration. LDL heterogeneity appears to be regulated by complex metabolic pathways, which are further modulated by common genetic variability.
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| 13. |
- Skoglund, Camilla, 1977-
(författare)
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Autoantibodies related to type 1 diabetes in children
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes is an autoimmune disease resulting from destruction of the insulin producing beta cells in the pancreas. The patients need life-long heavy treatment and still complications, both acute and later in life, are common. The incidence of type 1 diabetes has increased rapidly during the last decades, especially among young children. The disease can be predicted by genes predisposing type 1 diabetes, mainly human leukocyte antigen (HLA) genes, together with presence of autoantibodies to beta-cell antigens, where multiple autoantibodies confer the highest risk. A number of immune system intervention trials are now ongoing aiming to halt the progression of the inflammatory process in the beta cells.This thesis aimed to investigate the prevalence and levels of autoantibodies in healthy children and in children with type 1 diabetes. Another aim was to study different properties of one of these autoantibodies, such as to which epitopes the antibodies bind and the distribution of immunoglobulin (Ig)-G subclasses, after immunomodulatory treatment in children with type 1 diabetes.We found that positivity to autoantibodies against glutamic acid decarboxylase (GADA) and tyrosine phosphatase like protein islet antigen-2 (IA-2A) was associated with HLA risk genotypes in 5-year old children from the general population. HLA risk genotypes seemed important for persistence of autoantibodies and for development of type 1 diabetes, while emergence of autoantibodies, especially transient autoantibodies, seemed to be more influenced by environmental factors. Improved methods for detection of autoantibodies are needed, for prediction of diabetes and for identification of high-risk individuals suitable for prevention treatments. Therefore, an assay for measurement of insulin autoantibodies (IAA), based on surface plasmon resonance (SPR), was developed. The main advantages of this method are that there is no need for labelling and that it is time-saving compared to the traditionally used radioimmunoassay (RIA), but further development of the method is needed.Treatment with GAD-alum (Diamyd) in children with type 1 diabetes has shown to preserve residual insulin secretion. This clinical effect was accompanied by an increase in GADA levels. We investigated the epitope reactivity of GADA in both GAD-alum and placebo treated children, and found that binding to one of the tested epitopes was temporarily increased after injection of GAD-alum. This result suggests that the quality of GADA was, to some extent, transiently affected by the treatment. On the other hand, no changes in binding to epitopes associated with stiff person syndrome (SPS) were observed, which together with the lack of change in GAD65 enzyme activity further strengthens the safety of the treatment. We also observed that the distribution of IgG subclasses was changed by GAD-alum treatment, with a lower proportion of IgG1 and higher IgG3 and IgG4. Lower IgG1 and higher IgG4 suggest a temporary switch towards a protective Th2 immune response, which has previously been observed in the same individuals for other immunological markers.In conclusion, measurement of autoantibodies related to type 1 diabetes is an important tool for studying the autoimmune process in pre-diabetic and type 1 diabetic children. In addition to the use as markers of disease progression, the autoantibodies may be used for studying the effects of immunomodulatory treatments on the humoral immune response.
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| 14. |
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| 15. |
- Skoglund, Camilla, et al.
(författare)
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GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes
- 2012
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Ingår i: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 13:3, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. Previously we have shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by an increase in GAD autoantibody (GADA) titers. The aim of the present study was to investigate whether GAD-alum treatment affected the GADA epitope pattern. Methods. Serum samples of patients treated with GAD-alum (n=33) or placebo (n=27), at baseline and 1, 3, 9, and 15 months after initiation of treatment, were tested for their binding capacity to specific GADA epitopes in an epitope specific radioligand-binding assay with six GAD65-specific recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78 and N-GAD65 mAb). Results. For the period included in this study (baseline to 15 months) no difference in variability of binding to any of the tested rFab were observed. However, a higher median response to the b96.11-defined epitope in the first 3 months after the initial injection was observed in GAD-alum treated patients (-8.1%, min -72.4%, max 39.6%) compared to patients receiving placebo (1.5%, min -28.3%, max 28.6%) (p=0.02). This effect was especially evident in GAD-alum treated patients who experienced an increase of more than 100% in their GADA titer from baseline to 3 months (n=27), where we observed an 10.8% (-10.8%, min -72.4%, max 30.5%) increase in binding to the b96.11 epitope over the first 3 months post initial injection (p=0.04). Subsequently the recognition of the b96.11-defined epitope in the GAD-alum group decreased between 3 and 15 months (8.3%, min -17.1%, max 36.7%) compared to the placebo group (-2.4%, min -32.8%, max 30.1%) (p<0.05) and returned to levels similar to that observed at baseline. Correlations between GADA titer and epitope binding for b96.11 and DPD were observed in the placebo group, but not in the GADalum group, at 3 and 15 months after initial treatment. Conclusions/interpretation. We conclude that administration of GAD-alum temporarily induced increased binding to one epitope specificity of GADA.
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| 16. |
- Skoglund, Camilla, 1977-, et al.
(författare)
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Increase of Neutrophil Extracellular Traps, Mitochondrial DNA and Nuclear DNA in Newly Diagnosed Type 1 Diabetes Children but Not in High-Risk Children
- 2021
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Ingår i: Frontiers in Immunology. - Lausanne, Switzerland : Frontiers Media S.A.. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil extracellular traps (NETs) and mitochondrial DNA (mtDNA) are inflammatory mediators involved in the development of type 1 diabetes (T1D). Pancreas-infiltrating neutrophils can release NETs, contributing to the inflammatory process. Levels of NETs are increased in serum from patients with T1D and mtDNA is increased in adult T1D patients. Our aim was to investigate extracellular DNA (NETs, mtDNA and nuclear DNA) in children with newly diagnosed T1D and in children at high risk of the disease. We also elucidated if extracellular DNA short after diagnosis could predict loss of endogenous insulin production. Samples were analysed for mtDNA and nuclear DNA using droplet digital PCR and NETs were assessed by a NET-remnants ELISA. In addition, in vitro assays for induction and degradation of NETs, as well as analyses of neutrophil elastase, HLA genotypes, levels of c-peptide, IL-1beta, IFN and autoantibodies (GADA, IA-2A, IAA and ZnT8A) were performed. In serum from children 10 days after T1D onset there was an increase in NETs (p=0.007), mtDNA (p<0.001) and nuclear DNA (p<0.001) compared to healthy children. The elevated levels were found only in younger children. In addition, mtDNA increased in consecutive samples short after onset (p=0.017). However, levels of extracellular DNA short after onset did not reflect future loss of endogenous insulin production. T1D serum induced NETs in vitro and did not deviate in the ability to degrade NETs. HLA genotypes and autoantibodies, except for ZnT8A, were not associated with extracellular DNA in T1D children. Serum from children with high risk of T1D showed fluctuating levels of extracellular DNA, sometimes increased compared to healthy children. Therefore, extracellular DNA in serum from autoantibody positive high-risk children does not seem to be a suitable biomarker candidate for prediction of T1D. In conclusion, we found increased levels of extracellular DNA in children with newly diagnosed T1D, which might be explained by an ongoing systemic inflammation.
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| 17. |
- Tabebi, Mouna, et al.
(författare)
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Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS
- 2022
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Ingår i: International Journal of Molecular Sciences. - Basel, Switzerland : MDPI. - 1661-6596 .- 1422-0067. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enzymes of tricarboxylic acid (TCA) have recently been recognized as tumor suppressors. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) cause pheochromocytomas and paragangliomas (PCCs/PGLs) and predispose patients to malignant disease with poor prognosis.Methods: Using the human pheochromocytoma cell line (hPheo1), we knocked down SDHB gene expression using CRISPR-cas9 technology.Results: Microarray gene expression analysis showed that >500 differentially expressed gene targets, about 54%, were upregulated in response to SDHB knock down. Notably, genes involved in glycolysis, hypoxia, cell proliferation, and cell differentiation were up regulated, whereas genes involved in oxidative phosphorylation (OXPHOS) were downregulated. In vitro studies show that hPheo1 proliferation is not affected negatively and the cells that survive by shifting their metabolism to the use of glutamine as an alternative energy source and promote OXPHOS activity. Knock down of SDHB expression results in a significant increase in GLUD1 expression in hPheo1 cells cultured as monolayer or as 3D culture. Analysis of TCGA data confirms the enhancement of GLUD1 in SDHB mutated/low expressed PCCs/PGLs.Conclusions: Our data suggest that the downregulation of SDHB in PCCs/PGLs results in increased GLUD1 expression and may represent a potential biomarker and therapeutic target in SDHB mutated tumors and SDHB loss of activity-dependent diseases.
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| 18. |
- Thorsten, Anja, 1974-, et al.
(författare)
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Ledarskap för lärande – en inramning
- 2022
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Ingår i: Ledarskap för lärande. - Linköping : Linköping University Electronic Press. - 9789179292881 ; , s. 7-9
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Thorsten, Anja, 1974-, et al.
(författare)
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Modell 1-projektets faser
- 2022
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Ingår i: Ledarskap för lärande. - Linköping : Linköping University Electronic Press. - 9789179292881 ; , s. 24-26
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Detta projekt har varit det som benämns som ett modell 1-projekt inom ramen för regionens arbete med ULF (utveckling, lärande och forskning). Modell 1 är ett praktiknära forskningsprojekt som sker i samverkan mellan Linköpings universitet och kommunerna i regionen. Det är tvååriga projekt som initieras av regionens skolchefsnätverk (Thorsten, 2021). Tanken är att modell 1-projekt ska resultera i forskning som ba-seras på de behov som identifieras i regionen och att även om alla?kommuner inte deltar aktivt i processen ska resultaten komma hela regionen till del. I detta kapitel beskrivs projektets övergripande process. Mer detaljerade beskrivningar av de metoder som har använts ges i respektive resultatkapitel.?
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| 20. |
- Thorsten, Anja, 1974-, et al.
(författare)
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Till nytta för vem och på vilket sätt?
- 2022
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Ingår i: Ledarskap för lärande. - Linköping : Linköping University Electronic Press. - 9789179292881 ; , s. 111-113
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I detta sista kapitel diskuterar vi den tänkbara nyttan av det vi kommit fram till i ULF-projektet?Ledarskap för lärande. Att vi kommit fram till att lärares sätt att leda undervisning kan påverkas,?utvecklas och förändras med stöd av ett kompetensutvecklingsprogram visas i resultatet. Där framkommer också likheter, skillnader och kvaliteter utifrån olika skattningar av ledarskap för lärande. Vidare visas att kompetensutvecklingen givit lärarna begrepp, modeller och teorier som tillskott i deras yrkesspråkliga verktygslåda. Så med detta sagt, åter till frågan om hur resultat som de ovan?nämnda kan bli användbara för olika läsare och målgrupper. Användbara i betydelsen att lära eller påminna om hur lärare på ett bättre sätt ska kunna leda undervisning (Samuelsson, Kilman, Lindqvist, Prytz, Sveider, Thorsten, Wedin, Karlberg, Andersson, Johansson & Tväråna, 2020) och bedriva ledarskap för lärande, så att alla elever får bättre förutsättningar för att lära sig. Vi resonerar fortsatt om fyra olika målgrupper (a) lärare, (b) skolledare, (c) forskare och (d) en undervisningsintresserad allmänhet.
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| 21. |
- Wickham, Abeni, et al.
(författare)
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Near-Infrared Emitting and Pro-Angiogenic Electrospun Conjugated Polymer Scaffold for Optical Biomaterial Tracking
- 2015
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Ingår i: Advanced Functional Materials. - : Wiley: 12 months. - 1616-301X .- 1616-3028. ; 25:27, s. 4274-4281
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Tidskriftsartikel (refereegranskat)abstract
- Noninvasive tracking of biomaterials is vital for determining the fate and degradation of an implant in vivo, and to show its role in tissue regeneration. Current biomaterials have no inherent capacity to enable tracing but require labeling with, for example, fluorescent dyes, or nanoparticles. Here a novel biocompatible fully conjugated electrospun scaffold is described, based on a semiconducting luminescent polymer that can be visualized in situ after implantation using fluorescence imaging. The polymer, poly [2,3-bis-(3-octyloxyphenyl)quinoxaline-5,8-diyl-alt -thiophene-2,5-diyl] (TQ1), is electrospun to form a fibrous mat. The fibers display fluorescence emission in the near-infrared region with lifetimes in the sub-nanosecond range, optimal for in situ imaging. The material shows no cytotoxic behaviors for embryonic chicken cardiomyocytes and mouse myoblasts, and cells migrate onto the TQ1 fibers even in the presence of a collagen substrate. Subcutaneous implantations of the material in rats show incorporation of the TQ1 fibers within the tissue, with limited inflammation and a preponderance of small capillaries around the fibers. The fluorescent properties of the TQ1 fibers are fully retained for up to 90 d following implantation and they can be clearly visualized in tissue using fluorescence and lifetime imaging, thus making it both a pro-angiogenic and traceable biomaterial.
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| 22. |
- Åkerman, Linda, et al.
(författare)
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Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group. However, serum miRNAs appeared to reflect glycemic status and ongoing islet auto-immunity in high-risk individuals, since several miRNAs were associated to glucose homeostasis and autoantibody titers. High-risk individuals progressing to clinical disease after the sampling could not be clearly distinguished from non-progressors, while miRNA expression in the type 1 diabetes group deviated significantly from high-risk individuals and healthy controls, perhaps explained by major metabolic disturbances around the time of diagnosis.
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