161-OR: Autoantibodies Directed to Deamidated Post-translationally Modified IA-2 Epitopes in Type 1 Diabetes

Autoimmune disorders such rheumatoid arthritis (RA) harbor autoantibodies against a variety of post-translationally modified (PTM) proteins. We aimed to investigate whether PTM epitopes of IA-2, a major autoantigen related to type 1 diabetes (T1D), are targeted by autoantibody responses. The extracellular domain of IA-2 (IA-2-ec) was synthesized incorporating deamidated amino acid residues (IA-2ec-PTM) previously found to elicit T cell responses in T1D patients. IA-2ec-PTM was then subjected to immunoprecipitation with sera from T1D patients. Notably, autoantibody reactivity towards IA-2ec-PTM was present in 28% of T1D patients as compared to ~9% of serum reactivity against the native IA-2ec. The area under the ROC curve (ROC AUC) of IA-2ec-PTM autoantibodies revealed that these autoantibodies can adequately distinguish between T1D patient and control groups (ROC AUC: 0.7132; P Disclosure M.J. Acevedo-Calado: None. S. Pietropaolo: None. L. Yu: None. A.W. Michels: Stock/Shareholder; Self; IM Therapeutics. M. Pietropaolo: None. Funding National Institutes of Health