Tetraspanin 7 autoantibodies in type 1 diabetes.

AIMS/HYPOTHESIS: Autoantibodies to pancreatic beta cell proteins are markers of asymptomatic type 1 diabetes. The aim was to determine whether autoantibodies to the beta cell protein tetraspanin 7 would improve the ability to identify autoimmunity against pancreatic beta cells. METHODS: Full length and external domain fragments of tetraspanin 7 were expressed as luciferase-tagged fusion proteins and used in immunoprecipitation assays to measure autoantibodies in samples from 363 patients with type 1 diabetes at onset of disease, 503 beta cell autoantibody negative first-degree relatives of patients, and 212 relatives with autoantibodies to insulin, glutamic acid decarboxylase, insulinoma antigen 2 or zinc transporter 8. RESULTS: Antibody binding was observed against the full length and external domains of tetraspanin 7, and was strongest against the full length protein. Autoantibodies that could be inhibited by untagged tetraspanin 7 were detected in 5 (1%) of 503 autoantibody negative relatives, 3 (3.2%) of 94 autoantibody negative patients, 95 (35.3%) of 269 autoantibody positive patients, 1 (1%) of 98 single autoantibody positive relatives and 25 (21.9%) of 114 multiple autoantibody positive relatives. Progression to diabetes did not differ between multiple autoantibody positive relatives with and without tetraspanin 7 autoantibodies. CONCLUSIONS/INTERPRETATION: Tetraspanin 7 is an autoantigen in type 1 diabetes. Tetraspanin 7 autoantibodies are a marker of type 1 diabetes, but provide minor additional value to existing autoantibodies in identifying beta cell autoimmunity.

Diet Quality during Infancy and Early Childhood in Children with and without Risk of Type 1 Diabetes: A DEDIPAC Study.

Previous studies have indicated that mothers of children at increased risk of type 1 diabetes (T1D) may modify their child's diet following risk notification. Our aim was to investigate the diet quality after notified of T1D risk in at-risk children compared to not-at-risk children. The quality of nutrient intake (PANDiet score) and food intake (analyzed by a newly developed score and the HuSKY score) were assessed using three-day dietary records collected for at-risk children (BABYDIET study, n = 109) and a matched sample of not-at-risk children (DONALD study, n = 205) at nine and 24 months of age. Nutrient and food intake quality were lower at nine months of age and food intake quality was lower at 24 months of age in at-risk than in not-at-risk children (p = 0.01 and p < 0.0001, respectively). The amount of added sugar was higher in at-risk children at both ages (p < 0.0001). In at-risk children, dietary quality was similar between children who were first exposed to gluten at six or 12 months of age. Despite being notified about their child's risk of T1D, the child's mother did not switch to healthier diets compared with not-at-risk mothers.

A divergent population of autoantigen-responsive CD4+ T cells in infants prior to ß cell autoimmunity.

Autoimmune diabetes is marked by sensitization to ß cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in ß cell antigen-responsive CD4+ T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of ß cell antigen-responsive naïve CD4+ T cells from children who developed ß cell autoimmunity was found in infancy, well before the appearance of ß cell antigen-specific memory T cells or autoantibodies. The signature resembled a pre-T helper 1 (TH1)/TH17/T follicular helper cell response with expression of CCR6, IL21, TBX21, TNF, RORC, EGR2, TGFB1, and ICOS, in the absence of FOXP3, IL17, and other cytokines. The cells transitioned to an IFNG-TH1 memory phenotype with the emergence of autoantibodies. We suggest that the divergent naïve T cell response is a consequence of genetic or environmental priming during unfavorable perinatal exposures and that the signature will guide future efforts to detect and prevent ß cell autoimmunity.