GAD65 Autoantibody Immune Responses in Newly Diagnosed Type 1 Diabetes Children and in GADA Positive Children from General Population
Year: 2018
Type: dissertation
Abstract: Type 1 Diabetes is an autoimmune disease caused by the destruction of insulin secreting beta cells in pancreas. There are at least 50 potentially causal genes, but environmental factors act as the trigger. Before and after Type 1 Diabetes has developed, autoantibodies start appearing in the bloodstream, which could potentially predict the risk of developing the disease. The four major autoantibodies are: IAA, GADA, IA-2A and ZnT8A. \n \nThe focus of this study was GADA and its epitopes: many healthy people with no risk of developing Type 1 Diabetes are GADA positive. Serum samples were analyzed for autoantibodies with N-truncated GADA (tGADA). The method used in quantitative analysis of antibodies was radiobinding assay (RBA). Samples used in this study were from newly-diagnosed Type 1 Diabetes subjects in Finnish Pediatric Diabetes Register and from the DIABIMMUNE study 3–5-year-old children from the general population who were GADA positive. \n \nThe aim of this study was to determine whether specificity of the assay can be improved without losing sensitivity when using tGADA. Secondary goals were to determine which epitopes are the focus of immune response in multipositive, T1D positive and only-GADA positive subjects. \n \nCorrelation between GADA and tGADA assays was good (0.63–0.96). In all subjects, the immune response was directed towards M- and C-epitopes in those who were multipositive or T1D positive. Immune response against N-epitope was mostly found on subjects who were only-GADA positive and who were not multipositive or T1D positive. \n \nWith RBA, tGADA (96–585) recognizes T1D positives as well as GADA (1–585), but tGADA is better at recognizing those children who are at risk of developing type 1 diabetes or multipositivity in the future, thus tGADA is more specific, since it leaves out those who are only N-epitope positive. N-epitope positivity does not seem to have any effect on the risk of developing multiple autoantibodies or T1D.
Source: Theseus (Ammattikorkeakoulujen)
Author: Aleksi-Mikael Kivelä
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2808279654