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Träfflista för sökning "WFRF:(Wahlberg Jeanette) ;pers:(Ludvigsson Johnny)"

Sökning: WFRF:(Wahlberg Jeanette) > Ludvigsson Johnny

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1.
  • Barcenilla, Hugo, et al. (författare)
  • Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes
  • 2021
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes. 
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2.
  • Bélteky, Malin, et al. (författare)
  • Maternal respiratory infections in early pregnancy increases the risk of type 1 diabetes
  • 2020
  • Ingår i: Pediatric Diabetes. - : Hindawi Publishing Corporation. - 1399-543X .- 1399-5448. ; 21:7, s. 1193-1201
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/objective: Is exposure to maternal infections and use of antibiotics in the prenatal period associated with increased risk of T1D, regardless of genetic risk?Methods: Data on infections and use of antibiotics during pregnancy were collected from questionnaires at birth from parents to 16 292 children in the All Babies in Southeast Sweden (ABIS) cohort and validated against national diagnosis registers. As of November 2017, 137 ABIS children had developed T1D, 72 boys and 65 girls (0.8% of the original cohort).Results: More cases were born in spring and summer than fall and winter. However, onset of T1D appeared to be more common in either summer or winter. In univariate analyses, respiratory tract infection in the first trimester (P = .002) and gastroenteritis during pregnancy (P = .04) were associated with later risk of T1D in the offspring. Other types of infection or antibiotic treatment were not associated with an increased risk. In a multiple logistic regression model, a mother with an autoimmune disease (P < .001), father with T1D (P < .001) and respiratory tract infection during the first trimester (P = .005) remained as risk factors for T1D in the offspring. In children with neutral HLA alleles antibiotic treatment may increase the risk of T1D (P = .01, OR 3.46, 95% CI 1.25-9.55).Conclusions: In the general population there seems to be an association between seasonal maternal respiratory tract infection in the first trimester of pregnancy and later risk of T1D in the offspring. HLA may play a role for the effect of exposure to infections and antibiotics.
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3.
  • Casas, Rosaura, et al. (författare)
  • Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients
  • 2020
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 μg GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD65-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC < 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8+ T cells activation. Patients with poorer clinical response had higher baseline levels of GAD65-induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment. 
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4.
  • Casas, Rosaura, 1954-, et al. (författare)
  • Intra-lymphatic administration of GAD-alum in type 1 diabetes : long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial)
  • 2022
  • Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 59:5, s. 687-696
  • Tidskriftsartikel (refereegranskat)abstract
    •  Aim: To evaluate the long-term effect of intra-lymphatic administration of GAD-alum and a booster dose 2.5 years after the first intervention (DIAGNODE Extension study) in patients with recent-onset type 1 diabetes.Methods: DIAGNODE-1: Samples were collected from 12 patients after 30 months who had received 3 injections of 4 μg GAD-alum into a lymph node with one-month interval. DIAGNODE Extension study: First in human, a fourth booster dose of autoantigen (GAD-alum) was given to 3 patients at 31.5 months, who were followed for another 12 months. C-peptide was measured during mixed meal tolerance tests (MMTTs). GADA, IA-2A, GADA subclasses, GAD65-induced cytokines, PBMCs proliferation and T cells markers were analyzed.Results: After 30-month treatment, efficacy was still seen in 8/12 patients (good responders, GR). Partial remission (IDAA1c < 9) had decreased compared to 15 months, but did not differ from baseline, and HbA1c remained stable. GAD65-specific immune responses induced by the treatment started to wane after 30 months, and most changes observed at 15 months were undetectable. GADA subclasses IgG2, IgG3 and IgG4 were predominant in the GR along with IgG1. A fourth intra-lymphatic GAD-alum dose to three patients after 31.5 months gave no adverse events. In all three patients, C-peptide seemed to increase the first 6 months, and thereafter, C-peptide, HbA1c, insulin requirement and IDAA1c remained stable.Conclusion: The effect of intra-lymphatic injections of GAD-alum had decreased after 30 months. Good responders showed a specific immune response. Administration of a fourth booster dose after 31.5 months was safe, and there was no decline in C-peptide observed during the 12-month follow-up.
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5.
  • Dietrich, Fabricia, et al. (författare)
  • Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset Type 1 diabetes
  • 2022
  • Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 38:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for Type 1 diabetes (T1D). Studies with GAD-alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD-alum into the lymph nodes, aimed to optimize antigen presentation, has shown promising results in an open-label clinical trial. Here we compared the immune response of the individuals included in the trial with a group who received GAD-alum subcutaneously in a previous study.Materials and methods: Samples from T1D individuals collected 15 months after administration of either three doses 1 month apart of 4 μg GAD-alum into lymph nodes (LN, n=12) or two doses one month apart of 20 μg subcutaneously (SC, n=12) were studied. GADA, GADA subclasses, GAD65 -induced cytokines, PBMCs proliferation and T cells markers were analyzed.Results: Low doses of GAD-alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterized by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3 and IgG4 proportion, higher GAD65 -induced secretion of IL-5, IL-10 and TNF-α and reduction of cell proliferation and CD8+ T cells. These changes were not observed after subcutaneous injections of GAD-alum.Conclusions: GAD-specific immune responses 15 months after lymph node injections of GAD-alum differed from the ones induced by subcutaneous administration of the same autoantigen.
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6.
  • Gullstrand, Camilla, 1977-, et al. (författare)
  • Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study
  • 2008
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 9:3 PART 1, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.
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7.
  • Holmberg, Hanna, et al. (författare)
  • Short duration of breast-feeding as a risk-factor for beta-cell autoantibodies in 5-year-old children from the general population
  • 2007
  • Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 97:1, s. 111-116
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and beta-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tryosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2.09, 95% CI 1.45, 3.02; P<0.000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2.89, 95% CI 1.81, 4.62, P<0.000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2.01, 95% CI 1.08, 3.73; P=0.028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3.50, 95% CI 1.38, 8.92, P=0.009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1.84, 95% CI 1.01, 3.37; P=0.047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for beta-cell autoantibodies in children from the general population suggest that breast-feeding modifies the risk of beta-cell autoimmunity, even years after finishing breast-feeding.
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8.
  • Holmberg, Hanna, et al. (författare)
  • Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population
  • 2007
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 97:1, s. 111-116
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and β-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2-09, 95% CI 1-45, 3-02; P<0-000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2-89, 95% CI 1-81, 4-62; P<0-000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2-01, 95% CI 1-08, 3-73; P = 0-028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3-50, 95% CI 1-38, 8-92; P = 0-009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1-84, 95% CI 1-01, 3-37; P = 0-047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for β-cell autoantibodies in children from the general population suggests that breast-feeding modifies the risk of β-cell autoimmunity, even years after finishing breast-feeding.
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9.
  • Hyllienmark, Lars, et al. (författare)
  • Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes
  • 2013
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:10, s. 3187-3194
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.
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10.
  • Ludvigsson, Johnny, 1943-, et al. (författare)
  • Diabetes-related autoantibodies in cord blood from children of healthy mothers have disappeared by the time the child is one year old
  • 2002
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 289-292
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoantibodies found in cord blood in children who later develop diabetes might be produced by the fetus. If so, continuous autoantibody production would still be expected in these children at one year of age. We decided to determine autoantibodies in cord blood and to see whether they persisted in these children at one year. Autoantibodies against GAD65 (glutamic acid decarboxylase) and IA-2 (tyrosine phosphatase) in cord blood were determined in 2,518 randomly selected children. Forty-nine (1.95%) were positive for GAD65 antibodies, 14 (0.56%) were positive for IA-2 antibodies, and 3 of them were positive for both GAD and IA-2. Four of the mothers of children with GAD65 autoantibodies in cord blood (8.2%) had type 1 diabetes as did 5 mothers of children with IA-2 antibodies (35.7 %), but only 0.4% of the mothers had type 1 diabetes in the autoantibody-negative group (P < 0.001). Information on infections during pregnancy was available in 2,169 pregnancies. In the autoantibody-positive group, 31.5% had an infection during pregnancy, which was more common than in the autoantibody-negative group of 500 children with the lowest values (20.1%; P < 0.04). At one year follow-up nobody of those with positive cord blood had GAD65 or IA-2 autoantibodies. We conclude that most autoantibodies found in cord blood samples of children are probably passively transferred from mother to child. Antibody screening of cord blood cannot be used to predict diabetes in the general population. Infections during pregnancy may initiate an immune process related to diabetes development.
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