Virella Gabriel, Colglazier Joan, Chassereau Charlyne, Hunt Kelly J, Baker Nathaniel L, Lopes-Virella Maria F
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
J Immunoassay Immunochem. 2013;34(1):61-74. doi: 10.1080/15321819.2012.683500.
Modified lipoproteins are able to induce inflammatory reactions through innate immunity pathways and are immunogenic, leading to an autoimmune response that results in the formation of proinflammatory immune complexes. The measurement of circulating oxidized lipoproteins and corresponding antibodies has, therefore, been proposed as an approach to assess the risk for complications in patients with diabetes and for the risk of cardiovascular disease in the general population. However, the majority of modified low density lipoprotein (LDL) in the peripheral circulation exists in the form of immune complexes, and this is a significant obstacle for the measurement of modified LDL and the corresponding antibodies. In this manuscript, we describe in detail the methodology developed by our group for isolation and fractionation of circulating immune complexes (IC), allowing the accurate assay of different LDL modifications. This approach has resulted in several studies showing that the levels of modified LDL are risk factors with a stronger association to diabetic retinopathy, nephropathy, and macrovascular disease. Ongoing research is focused on evaluating the predictive power of modified LDL levels for the development or progression of atherosclerotic cardiovascular disease in other patient populations and on the simplification of the assay to make it more applicable to diagnostic laboratories.
修饰脂蛋白能够通过固有免疫途径诱导炎症反应，且具有免疫原性，会引发自身免疫反应，进而导致促炎性免疫复合物的形成。因此，循环氧化脂蛋白及相应抗体的检测已被提议作为评估糖尿病患者并发症风险以及普通人群心血管疾病风险的一种方法。然而，外周循环中大多数修饰的低密度脂蛋白（LDL）以免疫复合物的形式存在，这是检测修饰LDL及相应抗体的一个重大障碍。在本手稿中，我们详细描述了我们团队开发的用于分离和分级循环免疫复合物（IC）的方法，该方法能够准确测定不同的LDL修饰。这种方法已促成多项研究表明，修饰LDL水平是与糖尿病视网膜病变、肾病和大血管疾病关联更强的危险因素。正在进行的研究聚焦于评估修饰LDL水平对其他患者群体动脉粥样硬化性心血管疾病发生或进展的预测能力，以及简化检测方法使其更适用于诊断实验室。
