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


Address for correspondence: Eiji Kawasaki, M.D., Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Voice: 81-95-819–7550; fax: 81-95-819-7552.


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.