Humoral Immune Response to Islet Autoantigens in Japanese Patients with Type 1 Diabetes

In this study, we evaluated autoantibodies to IA‐2 (IA‐2As), glutamic acid decarboxylase 65 (GADAs), and islet cell antibodies (ICAs) in 233 patients with type 1 diabetes (M:F = 90:143, mean duration 4.0 ± 6.7 yr) as a cross‐sectional study. Of 233 patients with type 1 diabetes, IA‐2A was detected in 58% of patients with duration within 2 weeks, 61% of patients with duration <1 yr, 41% of patients with diabetes for 1–3 yr, 29% for 4–9 yr, and 21% for ≥10 yr. These prevalences were similar to those of ICA, while the prevalence of GADA was not influenced by duration of diabetes with positivity of 63–74%. Thus, as the duration of diabetes became longer, the frequency of GADA + /IA‐2A − patients increased and the frequency of GADA + /IA‐2A + patients decreased. However, the frequency of GADA − /IA‐2A + patients was not influenced by duration of diabetes. The prevalence of IA‐2A was significantly higher in abrupt‐onset group (68%, n = 79) compared to the slowly progressive group (23%, n = 22) in new‐onset patients ( P = 0.0001). However, there was no difference in the IA‐2A frequency between these two groups (abrupt‐onset 26%, n = 53 vs. slowly progressive 24%, n = 21) in patients with long‐standing disease, suggesting that IA‐2A positivity might persist in patients with slowly progressive type 1 diabetes. These results emphasize the heterogeneity of humoral autoimmunity to protein tyrosine phosphatase–like molecules, but not to GAD, in patients with type 1 diabetes.