Linked Life Data

8666150

Source:http://linkedlifedata.com/resource/pubmed/id/8666150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1996-8-6
pubmed:abstractText
IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what beta-cell antigens autoreactive lymphocytes become activated during early disease. We conducted a prospective study from birth, BABY-DIAB, among children of mothers with IDDM or gestational diabetes or fathers with IDDM, and we investigated the temporal sequence of antibody responses to islet cells (ICA), insulin (IAA), GAD (GADA), and the protein tyrosine phosphatase IA-2/ICA512 (IA-2A). Of 1,019 children included at birth, we have currently followed 513 to the age of 9 months, 214 to the age of 2 years, and 37 to the age of 5 years. At birth, all antibody specificities were frequent in newborns of diabetic mothers but not fathers and are suggested to be transplacentally acquired because they are strongly correlated with antibody levels in their diabetic mothers. In early childhood, antibody levels were <99th percentile of control subjects in the majority of children. However, 37 children exhibited elevated antibody levels; these were most frequently detected at the age of 2 years. The antibody prevalence at age 2 years was 2.3% for ICA, 7% for IAA, 4.2% for GADA, and 2.8% for IA-2A (8.9% positive for at least one antibody). Children of diabetic fathers were positive for at least one antibody more frequently than were children of diabetic mothers (9 months of age: 8.5 vs. 3.6%; 2 years of age: 16.7 vs. 7.9%). There was no specific sequence in the appearance of positive autoantibodies, but 13 (35%) antibody-positive cases already had more than one ICA before the age of 2 years and 7 (19%) showed reactivity to three islet cell antigens before age 5 years. The presence of multiple antibodies confers high risk for the future development of diabetes; three of six children who exhibited positive antibody responses to all four antibodies tested and another child with two positive antibodies developed clinical diabetes at the ages of 13, 21, and 27 months and 5 years. We conclude that loss of tolerance to beta-cell autoantigens and appearance of autoimmune phenomena occur very early in life in individuals with genetic susceptibility for IDDM. Screening programs to identify candidates for disease-prevention therapies can therefore be focused on this young age-group, in whom the disease process may be less advanced and who may therefore be best suited to such therapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
967-73
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8666150-Animals, pubmed-meshheading:8666150-Antibody Formation, pubmed-meshheading:8666150-Autoantibodies, pubmed-meshheading:8666150-Autoimmunity, pubmed-meshheading:8666150-Diabetes, Gestational, pubmed-meshheading:8666150-Diabetes Mellitus, Type 1, pubmed-meshheading:8666150-Fathers, pubmed-meshheading:8666150-Female, pubmed-meshheading:8666150-Follow-Up Studies, pubmed-meshheading:8666150-Glutamate Decarboxylase, pubmed-meshheading:8666150-Humans, pubmed-meshheading:8666150-Infant, Newborn, pubmed-meshheading:8666150-Insulin Antibodies, pubmed-meshheading:8666150-Islets of Langerhans, pubmed-meshheading:8666150-Male, pubmed-meshheading:8666150-Mice, pubmed-meshheading:8666150-Mice, Inbred NOD, pubmed-meshheading:8666150-Mothers, pubmed-meshheading:8666150-Nuclear Family, pubmed-meshheading:8666150-Pregnancy, pubmed-meshheading:8666150-Pregnancy in Diabetics, pubmed-meshheading:8666150-Prospective Studies, pubmed-meshheading:8666150-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:8666150-Protein Tyrosine Phosphatases, pubmed-meshheading:8666150-Time Factors
pubmed:year
1996
pubmed:articleTitle
Perinatal autoimmunity in offspring of diabetic parents. The German Multicenter BABY-DIAB study: detection of humoral immune responses to islet antigens in early childhood.
pubmed:affiliation
Diabetes Research Institute, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Multicenter Study