Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial.

Aims/hypothesis: Oral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes. Here, oral insulin was given as antigen-specific immunotherapy before the onset of autoimmunity in children from age 6 months to assess its safety and immune response actions on immunity and the gut microbiome.

Maternal Type 1 Diabetes Reduces Autoantigen-Responsive CD4 T Cells in Offspring.

Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process.

Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families.

The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes ( = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, , was identified in FDR children compared with GP children.

GM-CSF producing autoreactive CD4 T cells in type 1 diabetes.

The phenotype of autoreactive T cells in type 1 diabetes is described as Th1, Th17 and/or Th21, but is largely uncharacterized. We combined multi-parameter cytokine profiling and proliferation, and identified GM-CSF producing cells as a component of the response to beta cell autoantigens proinsulin and GAD65. Overall cytokine profiles of CD4 T cell were not altered in type 1 diabetes.

Allele-specific methylation of type 1 diabetes susceptibility genes.

The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype.

Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies.

Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age.

Towards a generic procedure for the detection of relevant contaminants from waste electric and electronic equipment (WEEE) in plastic food-contact materials: a review and selection of key parameters.

Recently, traces of brominated flame retardants (BFRs) have been detected in black plastic food-contact materials (FCMs), indicating the presence of recycled plastics, mainly coming from waste electric and electronic equipment (WEEE) as BFRs are one of the main additives in electric applications. In order to evaluate efficiently and preliminary in situ the presence of WEEE in plastic FCMs, a generic procedure for the evaluation of WEEE presence in plastic FCMs by using defined parameters having each an associated importance level has been proposed. This can be achieved by combining parameters like overall bromine (Br) and antimony (Sb) content; additive and reactive BFR, rare earth element (REE) and WEEE-relevant elemental content and additionally polymer purity.

CD8 T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage.

CD8 T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8 T cells specific for the IGRP epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8 T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed.

Evidence of waste electrical and electronic equipment (WEEE) relevant substances in polymeric food-contact articles sold on the European market.

In order to confirm the possibility that recycled fractions from the waste electrical and electronic equipment (WEEE) stream were illegally entering the European market in black polymeric food-contact articles (FCAs), bromine quantification, brominated flame retardant (BFR) identification combined with WEEE-relevant elemental analysis and polymer impurity analysis were performed. From the 10 selected FCAs, seven samples contained a bromine level ranging from 57 to 5975 mg kg(-)(1), which is lower than expected to achieve flame retardancy. The BFRs that were present were tetrabromobisphenol A (TBBPA), decabromodiphenylether (decaBDE), decabromodiphenylethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE).

Low-dose photon irradiation alters cell differentiation via activation of hIK channels.

To understand the impact of ionizing irradiation from diagnostics and radiotherapy on cells, we examined K(+) channel activity before and immediately after exposing cells to X-rays. Already, low dose in the cGy range caused in adenocarcinoma A549 cells within minutes a hyperpolarization following activation of the human intermediate-conductance Ca(2+)-activated K(+) channel (hIK). The response was specific for cells, which functionally expressed hIK channels and in which hIK activity was low before irradiation.