AUTOANTIBODIES IN NEWLY DIAGNOSED DIABETIC CHILDREN IMMUNOPRECIPITATE HUMAN PANCREATIC-ISLET CELL-PROTEINS

AUTOANTIBODIES IN NEWLY DIAGNOSED DIABETIC CHILDREN IMMUNOPRECIPITATE HUMAN PANCREATIC-ISLET CELL-PROTEINS
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DOI:
10.1038/298167a0
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发表时间:
1982-01-01
期刊:
影响因子:
64.8
通讯作者:
LERNMARK, A
LERNMARK, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BAEKKESKOV, S;NIELSEN, JH;LERNMARK, A

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胰岛素依赖型糖尿病(IDD)患者在诊断时具有高发的针对朗格汉斯岛细胞的循环自身抗体1 - 4。胰岛内的炎症细胞(5)、对胰腺抗原反应的白细胞迁移抑制(6)以及与某些HLA-D/DR组织相容性抗原(7,8)的关联(7,8)也被观察到。由于自身抗体主要与β-细胞发生反应,因此似乎与致病相关,但具体的靶抗原尚未确定。在目前的研究中,我们确定了胰岛素依赖型糖尿病儿童的血清是否能够免疫沉淀人类胰岛细胞洗涤剂裂解物中的蛋白质。我们报道,10名新诊断的糖尿病儿童中有8名的血清持续免疫沉淀一种分子量(Mr)为~ 64,000 (64K)的蛋白质。从hla - dr3阳性供者的胰岛细胞中沉淀另一种蛋白(38K)。这两种蛋白均未在非糖尿病患者血清中析出,也未在人淋巴细胞裂解液的免疫沉淀物中检测到。这表明64K和/或38K蛋白成分可能代表胰岛素依赖型糖尿病的细胞特异性靶抗原。
Insulin-dependent diabetic (IDD) patients have a high prevalence of circulating autoantibodies against islet of Langerhans cells at the time of diagnosis1–4. Inflammatory cells within the islets5, leukocyte migration inhibition in response to pancreatic antigens6and an association with certain HLA-D/DR histocompatibility antigens7,8, have also been observed. It seems that the autoantibodies may be pathogenically relevant as they react primarily withβ-cells9, but the specific target antigen(s) have yet to be identified. In the present study we determined whether sera from insulin-dependent diabetic children are able to immunoprecipitate proteins from detergent lysates of human islet cells. We report that sera from 8 out of 10 newly diagnosed diabetic children consistently immunoprecipitate a protein having a molecular weight (Mr) of ∼64,000 (64K). An additional protein (38K) was precipitated from islet cells obtained from a HLA-DR3-positive donor. Neither of the proteins was precipitated by non-diabetic sera nor detected in immunoprecipitates from human lymphocyte lysates. It is suggested that the 64K and/or 38K protein components may represent cell-specific target antigens in insulin-dependent diabetes.