Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations
Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations
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DOI：
10.1002/art.20780
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Witztum, JL
中科院分区：
文献类型：
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作者：
Frostegård, J;Svenungsson, E;Witztum, JL
目标。心血管疾病伴过早动脉粥样硬化在系统性红斑狼疮（SLE）患者中很常见。我们之前发现氧化低密度脂蛋白（OxLDL）水平升高以及与OxLDL相关的自身抗体水平升高是女性SLE患者心血管疾病的危险因素。OxLDL自身抗体在SLE中很常见，并与抗心磷脂抗体（aCL）交叉反应。因此，我们假设一般SLE患者的脂质过氧化作用增强。147名女性SLE患者与60名年龄和性别匹配的对照组进行了比较。氧化磷脂单克隆抗体EO6用于测定LDL上的氧化表位。采用化学发光技术检测抗氧化低密度脂蛋白和丙二醛修饰LDL、心磷脂、氧化aCL的自身抗体。通过结合EO6测定，SLE患者LDL上的氧化磷脂水平高于对照组（P = 0.005）。OxLDL（如氧化磷脂/载脂蛋白B）水平与动脉疾病（P = 0.006）和肾脏表现（P = 0.04）相关。如前所述，aCL、OxLDL自身抗体和mda修饰LDL自身抗体水平在SLE中升高，且密切相关。这些SLE患者的抗心磷脂抗体主要识别氧化形式的心磷脂，提示心磷脂抗原表位与SLE患者的脂质过氧化有关。总的来说，SLE患者（特别是心血管疾病患者）与对照组相比，LDL上的表位有更多的氧化。此外，这些患者的aCL识别了脂质过氧化过程中产生的表位。因此，在氧化过程中产生的脂蛋白上的“新”自身抗原在SLE中存在，可能对早期心血管疾病的发展很重要，也可能对SLE中观察到的其他自身免疫性现象很重要。
Objective. Cardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low-density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross-react with anticardiolipin antibodies (aCL). We therefore hypothesized that lipid peroxidation is enhanced in patients with SLE in general.Methods. One hundred forty-seven female patients with SLE and 60 age- and sex-matched controls were compared. A monoclonal antibody to oxidized phospholipids, EO6, was used to determine oxidation epitopes on LDL. Anti-OxLDL and autoantibodies to malondialdehyde (MDA)-modified LDL, cardiolipin, and oxidized aCL were determined by chemiluminescence technique.Results. As determined by binding of EO6, patients with SLE had a higher level of oxidized phospholipids on LDL (P = 0.005) compared with controls. The level of OxLDL (e.g., oxidized phospholipid/ apolipoprotein B) was associated with arterial disease (P = 0.006) and renal manifestations (P = 0.04). As reported previously, levels of aCL, autoantibodies to OxLDL, and autoantibodies to MDA-modified LDL were enhanced and were closely correlated in SLE. Anticardiolipin antibodies from these SLE patients recognized mainly oxidized forms of cardiolipin, indicating that antigenic epitopes on cardiolipin are related to lipid peroxidation in patients with SLE.Conclusion. In general, patients with SLE (particularly those with cardiovascular disease) had more oxidized epitopes on LDL compared with controls. Furthermore, aCL in these patients recognized epitopes generated during lipid peroxidation. Thus, "neo" self antigens on lipoproteins, generated during oxidation, are present in SLE and may be of importance for the development of premature cardiovascular disease and possibly also for other autoimmune phenomena observed in SLE.