Sera from children with Type 1 diabetes mellitus react against a new group of antigens composed of lysophospholipids

Sera from children with Type 1 diabetes mellitus react against a new group of antigens composed of lysophospholipids
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DOI:
10.1159/000023440
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发表时间:
1999-08-01
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影响因子:
--
通讯作者:
Lévy-Marchal, C
Lévy-Marchal, C
中科院分区:
其他
文献类型:
--
作者:
Bleich, D;Polak, M;Lévy-Marchal, C

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与1型糖尿病相关的几种自身抗体及其相应的自身抗原先前已被鉴定。虽然肽抗原被更广泛地认识到,脂质抗原如硫苷脂和神经节苷脂也是糖尿病体液免疫应答的已知表位。1型糖尿病患者的胰岛细胞抗体(伊卡)是一种特异性的免疫球蛋白,可针对胰岛中的特定抗原,伊卡可能是1型糖尿病患者家族成员疾病的最佳预测标志物。本研究的目的是:(1)从猪胰腺中纯化含有伊卡表位的脂质;(2)表征这些脂质抗原,以及(3)在测定中使用纯化的脂质检测1型糖尿病患者的抗体。一个独特的4种溶血磷脂家族,1完全表征为溶血磷脂酰肌醇,部分抑制伊卡染色,因此被认为是伊卡免疫测定的候选抗原。使用斑点印迹免疫测定法,我们在46份糖尿病血清中的28份(61%)中检测到针对这些磷脂的抗体,而在28份非糖尿病血清中仅检测到1份假阳性(3.6%; p < 0.0001,比较糖尿病与非糖尿病血清)。因此,溶血磷脂免疫测定阳性存在于1型糖尿病患者的血清中。此外,我们检测到15 23 ICA阴性糖尿病血清(65.2%),表明我们的磷脂免疫测定与伊卡阳性不相关。版权所有(C)2000 S. Karger AG,巴塞尔。
Several autoantibodies related to Type 1 diabetes mellitus and their corresponding autoantigens have been previously identified. While peptide antigens are more widely recognized, lipid antigens like sulfatides and gangliosides are also known epitopes for the diabetic humoral immune response. Islet cell antibodies (ICA) in Type 1 diabetes are heterogeneous immunoglobulins directed against selected antigens in the islets of Langerhans, Moreover, ICA may be the best predictive marker of disease in family members of patients with Type 1 diabetes. The aims of this study were: (1) to purify lipids from porcine pancreas that contain ICA epitopes; (2) to characterize these lipid antigens, and (3) to use the purified lipids in an assay to detect antibodies in patients with Type 1 diabetes. A unique family of 4 lysophospho- lipids, 1 fully characterized as lysophosphatidylmyoinositol, partially inhibited ICA staining, and therefore, were considered to be candidate antigens for an ICA immunoassay. Using a dot blot immunoassay, we detected antibodies directed against these phospholipids in 28 out of 46 (61%) diabetic sera, while detecting only 1 false positive out of 28 nondiabetic sera (3.6%; p < 0.0001 comparing diabetic vs. nondiabetic serum). Therefore, lysophospholipid immunoassay positivity is present in sera of Type 1 diabetic patients. Furthermore, we detected 15 out of 23 ICA-negative diabetic sera (65.2%), showing that our phospholipid immunoassay does not correlate with ICA positivity. Copyright (C) 2000 S. Karger AG, Basel.