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Sökning: WFRF:(Forsander G.)

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11.
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14.
  • Gyllenberg, A, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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15.
  • Jonsdottir, Berglind, et al. (författare)
  • Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents
  • 2013
  • Ingår i: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 56:8, s. 1735-1742
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
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16.
  • Lindehammer, Sabina, et al. (författare)
  • Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
  • 2008
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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17.
  • Ludvigsson, Johnny, et al. (författare)
  • C-peptide in the classification of diabetes in children and adolescents
  • 2012
  • Ingår i: Pediatric Diabetes. - : John Wiley and Sons. - 1399-543X .- 1399-5448. ; 13:1, s. 45-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To report C-peptide results in newly diagnosed patients and the relation to clinical diagnosis of diabetes. less thanbrgreater than less thanbrgreater thanMethods: A nation-wide cohort, the Better Diabetes Diagnosis study was used to determine serum C-peptide at diagnosis in 2734 children and adolescents. Clinical data were collected at diagnosis and follow-up. C-peptide was determined in a validated and controlled time-resolved fluoroimmunoassay. less thanbrgreater than less thanbrgreater thanResults: The clinical classification of diabetes, before any information on human leukocyte antigen, islet autoantibodies, or C-peptide was received, was type 1 diabetes (T1D) in 93%, type 2 diabetes (T2D) in 1.9%, maturity onset diabetes of the young (MODY) in 0.8%, secondary diabetes (0.6%), while 3.3% could not be classified. In a random, non-fasting serum sample at diagnosis, 56% of the patients had a C-peptide value andgt; 0.2 nmol/L. Children classified as T2D had the highest mean C-peptide (1.83 + 1.23 nmol/L) followed by MODY (1.04 +/- 0.71 nmol/L) and T1D (0.28 +/- 0.25 nmol/L). Only 1/1037 children who had C-peptide andlt; 0.2 nmol/L at diagnosis was classified with a type of diabetes other than T1D. Predictive value of C-peptide andgt; 1.0 nmol/L for the classification of either T2D or MODY was 0.46 [confidence interval 0.37-0.58]. less thanbrgreater than less thanbrgreater thanConclusions: More than half of children with newly diagnosed diabetes have clinically important residual beta-cell function. As the clinical diagnosis is not always straightforward, a random C-peptide taken at diagnosis may help to classify diabetes. There is an obvious use for C-peptide determinations to evaluate beta-cell function in children with diabetes.
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18.
  • Ludvigsson, Johnny, et al. (författare)
  • Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
  • 2011
  • Ingår i: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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20.
  • Picard, Robert G., et al. (författare)
  • Sweden
  • 2016
  • Ingår i: Who Owns the World's Media? Media Concentration and Ownership around the World. - Oxford : Oxford University Press. - 9780199987238 ; , s. 338-357
  • Bokkapitel (refereegranskat)
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