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  • 1
    In: Hormone and Metabolic Research, Georg Thieme Verlag KG, Vol. 49, No. 11 ( 2017-11), p. 892-898
    Abstract: 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. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman’s correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.
    Type of Medium: Online Resource
    ISSN: 0018-5043 , 1439-4286
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    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2017
    detail.hit.zdb_id: 2056576-8
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  • 2
    In: Diabetes, American Diabetes Association, Vol. 68, No. 4 ( 2019-04-01), p. 847-857
    Abstract: 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 (n = 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, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6–3.02] ) and for diabetes (HR 2.92 [95% CI 2.05–4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
    detail.hit.zdb_id: 1501252-9
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