ISLET AUTOANTIBODY MARKERS IN IDDM - RISK ASSESSMENT STRATEGIES YIELDING HIGH-SENSITIVITY
ISLET AUTOANTIBODY MARKERS IN IDDM - RISK ASSESSMENT STRATEGIES YIELDING HIGH-SENSITIVITY
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DOI：
10.1007/s001250050358
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发表时间：
1995-07-01
期刊：
影响因子：
8.2
通讯作者：
BOSI, E
中科院分区：
文献类型：
--
作者：
BONIFACIO, E;GENOVESE, S;BOSI, E
胰岛自身抗原的鉴定提供了一种可能性，即胰岛细胞抗体以外的抗体检测可用于评估胰岛素依赖型糖尿病（IDDM）的风险。本研究的目的是确定胰岛自身抗体标记物的组合，可以识别大多数未来的病例胰岛素依赖型糖尿病。在100名新诊断的IDDM患者、27名IDDM患者和83名对照者的血清中测量了胰岛细胞抗体、谷氨酸脱羧酶（GAD）抗体（65）、37，000/40，000 M（r）胰岛胰蛋白酶片段、羧肽酶-H和胰岛细胞自身抗原（伊卡）69。在88%的IDDM患者和81%的前IDDM患者中检测到胰岛细胞抗体，在70%的IDDM患者和89%的前IDDM患者中检测到GAD（65）抗体，在54%的IDDM患者和48%的前IDDM患者中检测到37，000/40，000 M（r）胰岛胰蛋白酶片段的抗体。后者仅与胰岛细胞抗体结合发现，并且在年轻发病病例中更常见。所有20名IDDM患者和3名有胰岛细胞抗体但无GAD（65）抗体的前IDDM受试者，其胰岛胰蛋白酶片段的抗体为37，000/40，000 M（r），除1名患者外，所有患者均在15岁之前发病。没有血清在体外强烈免疫沉淀翻译ICA 69或羧肽酶-H; 4%的患者抗ICA 69和11%抗羧肽酶-H水平高于对照受试者。研究结果表明，没有一种单一抗体的特异性像胰岛细胞抗体一样敏感，但是GAD（65）抗体和37，000/40，000 M（r）胰岛胰蛋白酶片段抗体的组合有可能识别90%以上的未来IDDM病例。这样的策略可能最终取代胰岛细胞抗体在人群筛查胰岛素依赖型糖尿病风险评估。
Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). The aim of this study was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)(65), 37,000/40,000 M(r) islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with pre-IDDM, GAD(65) antibodies in 70 % of IDDM patients and 89 % with pre-IDDM, and antibodies to 37,000/40,000 M(r) islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were found only in conjunction with islet cell antibodies and were more frequent in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell anti-bodies without GAD(65) antibodies had antibodies to 37,000/40,000 M(r) islet tryptic fragments, and all but one had disease onset before age 15 years. No sera strongly immunoprecipitated in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients had anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of the control subjects. The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD(65) antibodies and antibodies to 37,000/40,000 M(r) islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace islet cell antibodies in population screening for IDDM risk assessment.