Developments in the prediction of type 1 diabetes mellitus, with special reference to insulin autoantibodies.
The prodromal phase of type 1 diabetes is characterised by the appearance of multiple islet-cell related autoantibodies (Aab). The major target antigens are islet-cell antigen, glutamic acid decarboxylase (GAD), protein-tyrosine phosphatase-2 (IA-2) and insulin. Insulin autoantibodies (IAA), in contrast to the other autoimmune markers, are the only beta-cell specific antibodies. There is general consensus that the presence of multiple Aab (> or = 3) is associated with a high risk of developing diabetes, where the presence of a single islet-cell-related Aab has usually a low predictive value. The most commonly used assay format for the detection of Aab to GAD, IA-2 and insulin is the fluid-phase radiobinding assay. The RBA does not identify or measure Aab, but merely detects its presence. However, on the basis of molecular studies, disease-specific constructs of GAD and IA-2 have been employed leading to somewhat improved sensitivity and specificity of the RBA. Serological studies have shown epitope restriction of IAA that can differentiate diabetes-related from unrelated IAA, but current assays do not distinguish between disease-predictive and non-predictive IAA or between IAA and insulin antibodies (IA). More recently, phage display technology has been successful in identifying disease-specific anti-idiotopes of insulin. In addition, phage display has facilitated the in vitro production of antibodies with high affinity. Identification of disease-specific anti-idiotopes of insulin should enable the production of a high affinity reagent against the same anti-idiotope. Such a development would form the basis of a disease-specific radioimmunoassay able to identify and measure particular idiotypes, rather than merely detect and titrate IAA.
Franke
Bernd
B
Department of Diabetes/Endocrinology Level D, Rotherham General Hospital, UK. bernd.franke@rothgen.nhs.uk
Galloway
Tamara S
TS
Wilkin
Terry J
TJ
D000375:Aging; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000276:immunology*; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007130:Immunoglobulin Idiotypes; D007328:Insulin / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D019151:Peptide Library
D001323:Autoantibodies; D006680:HLA Antigens; C096322:ICA512 autoantibody; D007130:Immunoglobulin Idiotypes; D007328:Insulin; D019151:Peptide Library; D005968:Glutamate Decarboxylase