Diabetes & Metabolism Journal

Original Articles

Mesurement of GAD Antibodies using Radioligand Binding Assay, IRMA and RIA in Patients with Tye 1 Diabetes Mellitus.: In Kyu Lee, Hyoung Woo Lee, Kyu Chang Won, Hyun Dae Yoon, In Ho Cho, Ji Sung Yoon, Sang Yiup Nam, Jung Hyun Oh, Jin Cheol Park, Jae Hong Kim; Korean Diabetes J. 1999;23(3):278-287. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include insulin autoantibodies (IAAs), cytoplasmic islet cell antibodies (ICA) and GAD antibodies. Recently, there has been increasing interest in the use of glutamic acid decarboxylase antibodies (GADA) for the identification of subjects with increased risk of developing type 1 diabetes. GAD antibodies were first discovered in 1982 and is detected persistently after long duration of type 1 diabetes, whereas ICA is transient. However, because the classic immunoprecipitation assays of GAD antibodies is still rather time-consuming, a more simple and reproducible radiolignad binding assay (RBA) is has been widely used recently. The RIA (radioimmunoassay) and IRMA (immunoradiome- tricassay) for GAD antibodies using (125)I-labelled human GAD has been developed, The aim of the present study is to evaluate the usefulness of each methods. METHODS: We measured GAD antibodies by RBA with in vitro spathesized recombinani S-methio- nine-labelled GAD65, and protein A-sepharose to separate free from antibody-bound ligand and radioimmunoassay and immunoradiometric assay using 'I-labelled human GAD kit, in addition to measurement of ICAs by standard indirect immunofluorescence technique in 26 patients with type 1 diabetes(male 10, female 16, mean age 14 years) and 10 normal controls(male 5, female 5, mean age 15 years). RESULTS: The overall prevalence of GAD antibodies by RBA and RIA in patients with type 1 diabetes was 38% (10/26), respectively. The prevalence of GAD antibodies by IRMA in patients with type 1 diabetes was 31% (8/26). The frequency of GAD antibodies by RBA,IRMA and RIA increased as the JDF unit of ICA increased. There is a significant correlation between the GAD index (by RBA) and GAD concentration (by RIAand IRMA). CONCLUSION: These results suggest that GAD antibodies (by RIA or RBA or IRMA) is useful for screening and diagnosis of type 1 diabetes in Korean, but long-term prospective studies on large cohorts of patients is necessary.

Combined Measurements of Anti-ICA512 and Anti-GAD Antibodies in Insulin-dependent Diabetes Mellitus and Slowly Progressive Insulin-dependent Diabetes Mellitus in Korea.: Kyoung Ah Kim, Kyu Jung Ahn, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Phil Soo Oh, Dong Kyu Jin, Byung Tae Kim, Hae Joon Park, Kwang Won Kim, Myung Shik Lee; Korean Diabetes J. 1998;22(4):482-490. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is a chronic autoimmune disease in which circulating antibodies to various islet-specific antigens including autoantibodies to glutamic acid decarboxylase (GADAb), antibodies reacting with an islet tyrosine phosphatase-related molecule termed as ICA512 (ICA512Ab), and insulin autoantibodies are frequently detected. These autoantibodies could be useful for presymptomatic diagnosis of type 1 diabetes mellitus, and tbeir presence suggest some patients with atypical diabetes mellitus that appears to be more prevalent in Asian than in western countries have autoimmune characteristics. ICA512Ab was discovered in 1992 and, when combined with GADAb, may increase the diagnostic sensitivity in autoimmune diabetes. In an attempt to study the autoimmune feature of atypical diabetes mellitus, we studied the prevalence of ICA512Ab using an in vitro transcription and translation method in the patients with insulin-dependent diabetes mellitus (IDDM), slowly progressive insulin-dependent diabetes mellitus (SPIDDM) and non-msulin-dependent diabetes mellitus (NIDDM), and compared it with that of GADAb. METHODS: ICA512Ab were measured by a radioimmunoprecipitation method using in vitro transcribed and translated S-methionine-labeled ICA512. GADAb were measured using a commercial radioimmunoassay kit (RSR, United Kingdom). The subjects in this study consisted of 43 patients with IDDM, 32 with SPIDDM, and 40 witb NIDDM. Their mean age was 21.2+14.5 years, 50.1+17.1 years, 52.5+13.4 years, respectively. RESULTS: The prevalence of ICA512Ab and GADAb in IDDM was 29 % and 51 %, respectively. That in SPIDDM was 9 % and 29 %; in NIDDM, 0 % and 2.5 %, respectively. When two antibodies were combined, 60 % of IDDM and 50 % of SPIDDM had the autoantibodies. When we analyzed the prevalence of autoantibodies according to the duration of diabetes, the prevalence of ICA 512Ab in patients tested within 4 years after the rliagnosis and more than 4 years after the diagnosis was 35 % and 19 %, respectively in IDDM. And also that of GADAb was 59 % and 38 %, respectively. In SPlDDM, the prevalence of ICA512Ab was 13 % and 7 %, respectively, while that of GADAb was 67 % and 14 % (p<0.05), respectively. In IDDM, ICA512Ab were more frequently detected in patients younger than 15 years ot age (45 %) than in older ones (14%) (p<0.05) while the prevalence of GADAb was not different according to the age (55 % vs 44 %). CONCLUSION: ICA512Ab are detected in some patients with autoimmune diabetes, while their prevalence is lower than that of GADAb. However, ICA512Ab, in combination with GADAb, increases the sensitivity ot autoantibody tests in autoimmune diabetes. Some of SPIDDM have an autoimmune etiology.

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