Response to Comment on Mulukutla et al. Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of “A+” Subtypes of Ketosis-Prone Diabetes. Diabetes Care 2018;41:2637–2640

Abstract

We thank Dr. Heneberg (1) for the comments regarding our article (2) describing autoantibody responses to the IA-2 extracellular domain in ketosis-prone diabetes (KPD).\n\nWe agree that the intracellular domain of the neuroendocrine autoantigen IA-2 (amino acid residues 605–979) represents the immunodominant region of the molecule. In fact, both autoantibody and autoreactive T-cell responses from patients with type 1 diabetes recognize peptides localized within the intracellular domain of IA-2 (IA-2IC) (3). Nonetheless, we identified autoantibody and T-cell responses specifically directed to the IA-2 extracellular domain (IA-2EC) in individuals with or without antibodies against IA-2IC (4). Our recent studies demonstrate that IA-2EC is a target of humoral immune responses in a subgroup of patients with KPD (2). To demonstrate specificity of …