186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes

Background: Insulinoma antigen-2 (IA2) is a major self-antigen in T1D with post translational modification (PTM) of the extracellular domain (IA2ec) by deamidation eliciting T cell responses in T1D patients. Yet the autoantibodies (Abs) to these IA2ec PTM epitopes in T1D has not been studied. Methods: IA2ec protein containing all the four T-cell responsive deamidated Q>E epitopes (aa 198-216, 467-482, 523-536 and 545-562) was produced. Sera from 269 new onset T1D children (median age= 12.6yrs) and 3age-matched healthy children were tested for Abs to IA2ecQ>E and wide type (WT) IA2ec with radiobinding assay (RBA) . Results: The assay cut-offs were set at the 99th percentile for both IA2ecQ>E Ab and IA2ecWT Ab. In T1D children, positivity for IA2ecQ>E Ab was 60.6% (163/269) vs. IA2ecWT Ab 19.3% (52/269, PE Ab were significantly higher than IA2ecWT Ab (Fig) , 58% (91/157) vs. 15.3% (24/157, PE Ab is potentially a new novel predictive and diagnostic biomarker for T1D.