Kulmala P, Savola K, Petersen J S, Vähäsalo P, Karjalainen J, Löppönen T, Dyrberg T, Akerblom H K, Knip M
Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland.
J Clin Invest. 1998 Jan 15;101(2):327-36. doi: 10.1172/JCI119879.
An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.
对755名胰岛素依赖型糖尿病（IDDM）患儿的同胞进行了一项非选择性研究，以评估胰岛细胞抗体（ICA）、IA-2蛋白抗体（IA-2A）、谷氨酸脱羧酶65-kD异构体抗体（GADA）、胰岛素自身抗体（IAA）以及这些标志物组合的预测特征。我们还评估了组织化学ICA检测是否可以被其他标志物的联合检测所取代。在对索引病例进行诊断时或接近诊断时采集初始样本后的7.7年内，有32名同胞进展为IDDM（中位随访时间为9.1年）。ICA、IA-2A、GADA和IAA的阳性预测值分别为43%、55%、42%和29%，其敏感性分别为81%、69%、69%和25%。与其他三种抗体特异性不同，GADA水平与IDDM风险无关。有四种、三种、两种、一种或无抗体的同胞患IDDM的风险分别为40%、70%、25%、2%和0.8%。联合筛查IA-2A和GADA可识别出所有ICA阳性同胞中的70%，并且所有ICA阳性进展者对其他三种标志物中的至少一种也呈阳性。IA-2A和GADA联合分析的敏感性为81%，阳性预测值为41%。总之，联合筛查IA-2A和GADA可能会取代ICA检测，具有相当的敏感性、特异性和阳性预测值。对同胞患IDDM风险的准确评估很复杂，因为即使是所有具有四种抗体特异性的人也并非都会患该病，而且一些最初只有一种或无抗体的人也会进展为IDDM。
