Different Interaction of Onset Age and Duration of Type 1 Diabetes on the Dynamics of Autoantibodies to IA-2 and ZnT8.

AIM/INTRODUCTION This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2(IA-2A) and zinc transporter-8(ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes(T1D). METHODS Using bridging-type enzyme-linked immunosorbent assay(ELISA), IA-2A, ZnT8A, and glutamic acid decarboxylase autoantibodies(GADA) were evaluated in 269 patients with T1D (median onset age:18.2 years(range 0.8-86 years); median diabetes duration:7years(range 0-58 years)). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using Cochran-Armitage trend test and multivariate logistic regression analysis. RESULTS The prevalence of IA-2A, ZnT8A, and GADA in patients with duration of ≤3 years was 41.1%, 36.7%, 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration(P<0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, while GADA was more common in older patients. Multivariate logistic regression analysis revealed that there was significant interaction between the onset age and duration of diabetes in patients diagnosed at or younger than 10 years concerning all anti-islet autoantibodies(P<0.05). However, in subjects diagnosed in the middle tertile(11-30 years), interaction was significant only for ZnT8A, in those with late-onset(≥31 years) only for IA-2A. CONCLUSION The current study revealed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged younger than 10 years and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.