| 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. |
- Dittrich, Yvonne, et al.
(författare)
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Design for Change
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The report summarises the first year of the research project 'Design for Design in Use of Database Applications'. It focuses on end user tailoring and adaptable systems.
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| 3. |
- Nätt, Daniel, et al.
(författare)
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High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases
- 2015
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Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic link prospectively in children. Results: Here, we studied a homogenous group of 48 5-year-old children. By combining hair cortisol measurements (a well-documented biomarker for chronic stress), with whole-genome DNA-methylation sequencing, we show that high cortisol associates with a genome-wide decrease in DNA methylation and targets short interspersed nuclear elements (SINEs; a type of retrotransposon) and genes important for calcium transport: phenomena commonly affected in stress-related diseases and in biological aging. More importantly, we identify a zinc-finger transcription factor, ZNF263, whose binding sites where highly overrepresented in regions experiencing methylation loss. This type of zinc-finger protein has previously shown to be involved in the defense against retrotransposons. Conclusions: Our results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that this may affect future disease susceptibility by alterations in the epigenetic mechanisms that keep retrotransposons dormant. Future treatments for stress-and age-related diseases may therefore seek to target zinc-finger proteins that epigenetically control retrotransposon reactivation, such as ZNF263.
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| 4. |
- Olén, Ola, et al.
(författare)
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Urinary tract infections in pregnant women with coeliac disease
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - Oslo : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 42:2, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Previous research has indicated a link between coeliac disease (CD) and urinary tract infection (UTI). The objective of this study was to assess the risk of UTI and repeated episodes of UTI before the current pregnancy in women with diagnosed or undiagnosed CD. Material and methods. A national registry-based cohort study restricted to pregnant women was used in this investigation, with linkage between the Swedish National Medical Birth Registry and the National Inpatient Registry. We analysed the risk of UTI during pregnancy from 1973 to 1989 in 212 pregnancies to women who had received a diagnosis of CD prior to giving birth and in 786 pregnancies to women diagnosed after giving birth. We also assessed the risk of repeated episodes of UTI before the current pregnancy according to data in the national birth records of 1990-2001 in 617 women with CD diagnosed prior to giving birth and 109 women diagnosed after giving birth. Results. UTI during pregnancy: UTI occurred during 19,139/1,678,304 pregnancies to women who had never had a diagnosis of CD, compared with in 12/786 pregnancies to women with undiagnosed CD (adjusted odds ratio (AOR) =1.37; 95% CI =0.78-2.43; p=0.276) and in 0/212 pregnancies to women with diagnosed CD (AOR =0.06; 95% CI =0.00-8.94; p=0.277) (ORs adjusted for maternal age, parity, nationality and calendar period). Repeated episodes of UTI before the current pregnancy: among 692,991 women who had never had a diagnosis of CD, 74,776 reported repeated episodes of UTI, compared with 14/101 women with undiagnosed CD (AOR =1.39; 95% CI =0.79-2.45; p=0.255) and 69/566 women with diagnosed CD (AOR =1.02; 95% CI =0.79-1.32; p=0.864) (ORs adjusted for maternal age, parity, nationality, calendar period and civil status). Adjustment for smoking in a subset of patients with available data did not change the risk estimates. Conclusions. It cannot be ruled out that undiagnosed CD in pregnant women is associated with a small, increased risk of UTI. In pregnant women with diagnosed CD, there seems to be no increased risk of UTI.
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| 5. |
- Pihl, Mikael, et al.
(författare)
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GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients
- 2017
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Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 176, s. 114-121
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Tidskriftsartikel (refereegranskat)abstract
- Administration of Glutamic Acid Decarboxylase (GAD)(65) formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15 months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21 months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD(65)-induced proliferation, and frequencies of T cells with a GAD(65)-specific TCR in Swedes participating in the trial. Stimulation with GAD(65) induced activated T cells and also cells with a suppressive phenotype. Activated GAD(65)-specific effector T cells were detected by tetramer staining while the frequency of GAD(65)-specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25(+)CD127(+), but had no effect on CD25(hi)CD127(lo). Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD(65)-specific cells were mainly of activated phenotype. (C) 2017 Elsevier Inc. All rights reserved.
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| 6. |
- 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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