Borg H, Fernlund P, Sundkvist G
Department of Endocrinology, University of Lund, Malmö University Hospital, Sweden.
Clin Chem. 1997 Dec;43(12):2358-63.
Islet cell antibodies (ICA), the classical autoimmunity marker for insulin-dependent diabetes mellitus (IDDM), are detected in approximately 85% of children with recently diagnosed diabetes. Because the ICA assay is semiquantitative and difficult to standardize, alternative assays are needed. When glutamic acid decarboxylase 65 (GAD 65) was discovered as a major islet antigen, the measurement of antibodies to GAD 65 (GADA) was considered a good alternative to ICA. Recently, however, we showed that 1 in 3 ICA-positive diabetic patients do not have GADA. Now, antibodies against the protein tyrosine phosphatase-like protein IA2 (IA2-ab) have been detected in IDDM. To find out whether measurements of IA2-ab combined with those of GADA could detect autoimmunity to the same extent as ICA, we have measured all three kinds of antibodies (using radioligand binding assays for IA2-ab and GADA) in 100 recently diagnosed diabetic and 100 control children: ICA were found in 87, IA2-ab in 69, and GADA in 66 of the 100 diabetic patients, whereas in the 100 control children ICA were found in 2, IA2-ab in 1, and GADA in 3. Among the 87 ICA-positive patients, 45 (52%) had both IA2-ab and GADA, 21 (24%) had only IA2-ab, and 16 (18%) had only GADA, whereas 5 (6%) lacked both IA2-ab and GADA. Among the 13 ICA-negative patients, 1 (8%) had both IA2-ab and GADA, 2 (15%) had only IA2-ab, and 4 (31%) had only GADA. Thus, 6 of the 100 patients had neither ICA, IA2-ab, nor GADA. Combining the IA2-ab and GADA assays gave positive results for autoimmunity in 89 of the 100 patients, compared with 87 by the ICA assay. The combination of the IA2-ab and GADA assays appears to be an effective alternative to the ICA assay.
胰岛细胞抗体(ICA)是胰岛素依赖型糖尿病(IDDM)的经典自身免疫标志物,在近期确诊的糖尿病儿童中,约85%可检测到该抗体。由于ICA检测是半定量的且难以标准化,因此需要其他检测方法。当谷氨酸脱羧酶65(GAD 65)被发现是一种主要的胰岛抗原时,检测抗GAD 65抗体(GADA)被认为是ICA的良好替代方法。然而,最近我们发现,三分之一的ICA阳性糖尿病患者没有GADA。现在,在IDDM患者中已检测到针对蛋白酪氨酸磷酸酶样蛋白IA2的抗体(IA2-ab)。为了弄清楚IA2-ab与GADA联合检测是否能与ICA一样有效地检测自身免疫,我们对100名近期确诊的糖尿病儿童和100名对照儿童检测了所有这三种抗体(使用放射性配体结合法检测IA2-ab和GADA):100名糖尿病患者中,87人检测到ICA,69人检测到IA2-ab,66人检测到GADA;而在100名对照儿童中,2人检测到ICA,1人检测到IA2-ab,3人检测到GADA。在87名ICA阳性患者中,45人(52%)同时有IA2-ab和GADA,21人(24%)仅有IA2-ab,16人(18%)仅有GADA,而5人(6%)既没有IA2-ab也没有GADA。在13名ICA阴性患者中,1人(8%)同时有IA2-ab和GADA,2人(15%)仅有IA2-ab,4人(31%)仅有GADA。因此,100名患者中有6人既没有ICA、IA2-ab也没有GADA。IA2-ab和GADA联合检测在100名患者中有89人显示自身免疫阳性结果,而ICA检测为87人。IA2-ab和GADA联合检测似乎是ICA检测的有效替代方法。