Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus.
Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus.
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糖尿病患者血浆中糖基化蛋白的自身抗体。
DOI：
10.1073/pnas.81.10.3204
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发表时间：
1984
影响因子：
11.1
通讯作者：
Fisher,M
中科院分区：
文献类型：
--
作者：
Witztum,JL;Steinbrecher,UP;Kesaniemi,YA;Fisher,M
在实验动物和正常人中，非酶葡糖基化干扰低密度脂蛋白（LDL）受体对LDL的识别，并显著降低葡糖基化LDL的血浆清除率。然而，在选定的糖尿病受试者中，我们观察到葡萄糖基化LDL清除率的矛盾增加，表明免疫介导清除的可能性。免疫分析表明，在四个这样的糖尿病受试者研究的注射前血浆中的葡萄糖基化LDL的特异性抗体。这些抗体与其他糖基化蛋白质交叉反应，并特异性识别糖基化赖氨酸表位-即，葡萄糖赖氨酸这些数据表明，血浆或结构蛋白的非酶促葡糖基化可能使它们具有免疫原性，并导致产生不仅识别特定免疫原而且识别许多其他葡糖基化蛋白（包括葡糖基化组织蛋白）的自身抗体。这些发现可能与糖尿病患者血浆中免疫复合物的患病率增加以及糖尿病的晚期并发症有关。
Nonenzymatic glucosylation interferes with recognition of low density lipoprotein (LDL) by its receptor and markedly decreases the rate of plasma clearance of glucosylated LDL, both in experimental animals and in normal human subjects. However, in selected diabetic subjects we have observed a paradoxical increase in the clearance of glucosylated LDL, suggesting the possibility of immune-mediated clearance. Immunoassay demonstrated antibodies specific for glucosylated LDL in the preinjection plasma of each of four such diabetic subjects studied. These antibodies cross-react with other glucosylated proteins and recognize specifically the glucosylated lysine epitope--i.e., glucitollysine . These data suggest that nonenzymatic glucosylation of plasma or structural proteins may render them immunogenic and result in production of autoantibodies that recognize not only the particular immunogen but also many other glucosylated proteins, including glucosylated tissue proteins. These findings may be relevant to the increased prevalence of immune complexes in plasma of diabetic subjects and the late complications of diabetes mellitus.