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标题：Autoimmune response to advanced glycosylation end-products of human LDL
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作者：Gabriel Virella ; Suzanne R. Thorpe ; Nathan L. Alderson 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2003
卷号：44
期号：3
页码：487-493
DOI：10.1194/jlr.M200370-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Advanced glycosylation end-products (AGEs) are believed to play a significant role in the development of vascular complications in diabetic patients. One such product, AGE-LDL, has been shown to be immunogenic. In this report, we describe the isolation and characterization of human AGE-LDL antibodies from the sera of seven patients with Type 1 diabetes by affinity chomatography using an immobilized AGE-LDL preparation that contained primarily the AGE N^ε(carboxymethyl)lysine (CML, 14.6 mmol/mol lysine), and smaller amounts of N^ε(carboxyethyl)lysine (CEL, 2.7 mmol/mol lysine). The isolated antibodies were predominantly IgG of subclasses 1 and 3, and considered proinflammatory because of their ability to promote FcγR-mediated phagocytosis and to activate complement. We determined dissociation constants ( K _d) for the purified antibodies. The average K _d values (4.76 ± 2.52 × 10⁻⁹ mol/l) indicated that AGE-LDL antibodies are of higher avidity than oxidized LDL antibodies measured previously ( K _d = 1.53 ± 07 × 10⁻⁸ ml/l), but of lower avidity than rabbit polyclonal LDL antibodies ( K _d = 9.34 × 10⁻¹¹). Analysis of the apolipoprotein B-rich lipoproteins isolated with polyethylene glycol-precipitated antigen-antibody complexes from the same patients showed the presence of both CML and CEL, thus confirming that these two modifications are recognized by human autoantibodies. A comparative study of the reactivity of purified AGE-LDL antibodies with CML-LDL and CML-serum albumin showed no cross-reactivity.