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Clinical screening identifies autoimmune diabetes in adults
S. Fourlanos, C. Perry, L.C. Harrison, in collaboration with M. Stein, P.G. Colman, Department of Diabetes and Endocrinology, Royal Melbourne Hospital
Autoimmune diabetes in adults (ADA) is characterised by circulating pancreatic islet antibodies and progression to insulin treatment within several years of diagnosis. We studied 213 cases of adult-onset diabetes and identified five clinical features that were more frequent at diagnosis in ADA compared to type 2 diabetes: age of onset < 50 years, acute symptoms of hyperglycaemia, body mass index < 25, family history of type 1 diabetes, and family or personal history of related autoimmune conditions. The presence of at least two of these clinical features in adult-onset diabetes indicates a statistically higher risk of autoimmune diabetes and can be used to identify ADA .
HLA phenotypes differ in adults and children with autoimmune diabetes
S. Fourlanos, C. Perry, M. Honeyman, L.C. Harrison in collaboration with P.G. Colman, Department of Diabetes and Endocrinology, Royal Melbourne Hospital; M. Varney, B.D. Tait, Victorian Immunogenetics & Transplantation Service, The Royal Melbourne Hospital
The HLA-DR3 and-DR4 Class II alleles are strongly associated with the development of type 1 diabetes (T1D), accounting for up to 50% of the genetic risk. These alleles occur in higher frequency in both classic juvenile-onset T1D and autoimmune diabetes in adults (ADA), a slowly-progressive form of T1D characterized by adult-age onset. The age at diagnosis of classic T1D is inversely proportional to the number of HLA risk alleles. In comparing the frequencies of specific HLA alleles, we found a lower frequency of HLA-DR3 and -DR3,4 in ADA compared to juvenile T1D, which could explain the later onset of ADA.
TrialNet, an international consortium to prevent type 1 diabetes
L.C. Harrison, P.G. Colman, F. Williams, in collaboration with TrialNet Centers in the USA and Europe
TrialNet is a consortium of investigators funded by the NIH and JDRF to design and implement trials to prevent type 1 diabetes (T1D). Outside the USA, there are four international TrialNet Centers: in the UK, Finland, Italy-Germany and ourselves. We have initiated the TrialNet Natural History Study with 17 affiliate centres in Australia and New Zealand, to identify individuals at risk of T1D, who will be candidates for prevention trials. We are also about to commence a TrialNet study to compare tests of pancreatic beta-cell function in people with diagnosed T1D.
Identification and analysis of autoantigen-specific regulatory T cells
J.A. Dromey, H. Young, S.I. Mannering, L.C.Harrison
Regulatory T cells (Treg) are a subset of T lymphocytes that are important in controlling immune responses to self-antigens. No specific markers of Treg exist, making these cells difficult to study in human disease. We have isolated Treg clones specific for the type 1 diabetes autoantigen, GAD 65, from human blood. These clones are being analysed for molecular signatures that will allow us to distinguish Treg from other T cells. A means of identifying autoantigen-specific Treg will enable the study of these cells in autoimmune diseases such as type 1 diabetes and their evaluation as potential as therapeutic targets or diagnostic markers.
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