Distinct IA‐2 Autoantibody Epitope Recognition between Childhood‐Onset and Adult‐Onset Type 1 Diabetes

: Different autoimmune mechanisms may be involved in childhood- and adult-onset type 1 diabetes. Our aim was to explore the differences in IA-2 autoantibody epitope recognition between childhood- and adult-onset type 1 diabetes. Therefore, in vitro synthesized radiolabeled IA-2ic (amino acid 601-979), IA-2JM (amino acid 557-629), and IA-2PTP (amino acid 630-979) were used to analyze the IA-2 autoantibody epitope specificities in 93 patients with new-onset type 1 diabetes. Among 93 patients with type 1 diabetes the prevalences of autoantibodies to GAD, IA-2ic, and insulin were 69.9%, 58.1%, and 45.2%, respectively. The prevalence of IA-2ic autoantibodies in patients with childhood-onset type 1 diabetes (aged ≤18 years, n= 60) was significantly higher than that in patients with adult-onset diabetes (68.3 vs. 36.4%, P < 0.002). Ninety-two percent of type 1 diabetic patients positive for IA-2ic autoantibodies recognized the PTP domain of IA-2, whereas 8% reacted with the JM region only. Among 60 patients with childhood-onset type 1 diabetes, 2% recognized the JM region only, 48% bound the PTP domain of IA-2 only, and 18% recognized both JM and PTP epitopes. Among 33 patients with adult-onset diabetes, 9% recognized the IA-2JM only, 18% bound the IA-2PTP only, and 9% recognized both the IA-2JM and the IA-2PTP. IA-2PTP autoantibodies were prevalent in patients with childhood-onset type 1 diabetes. By contrast, the proportion of patients with the IA-2JM autoantibody only in type 1 diabetes who were positive for IA-2ic autoantibodies was significantly higher in adult-onset than in childhood-onset diabetes (P < 0.05). These results demonstrate that autoantibody recognition of the IA-2 epitope is distinct in childhood-onset and adult-onset type 1 diabetes.