Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus
Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus
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DOI：
10.1196/annals.1422.016
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Alves, J. Delgado
中科院分区：
文献类型：
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作者：
Batuca, J. R.;Ames, P. R. J.;Alves, J. Delgado
系统性红斑狼疮（SLE）患者血管疾病的发病率增加，氧化应激被认为是这种情况下的一个重要特征，尽管其潜在机制尚未完全了解。在这些患者中，脂蛋白和免疫系统之间的相互作用已经被提出，但大多数研究只关注抗氧化低密度脂蛋白的抗体。本研究旨在确定针对高密度脂蛋白（HDL）的抗体的存在，并确定这些抗体与HDL中存在的抗氧化酶对氧磷酶（PON）之间可能的关联。收集55例SLE患者的血浆，用酶联免疫吸附试验测定IgG型aHDL和抗载脂蛋白A-I（aApo A-I）抗体。在150名健康受试者的对照人群中进行了方法的标准化。血浆水平高于对照群体平均值的5个标准差被认为是阳性的。PON活性通过定量对硝基苯酚形成（μ mol/mL/min）来评估。SLE患者血清allDL（P < 0.0001）和aApo A-I（P < 0.0001）抗体滴度高于健康对照组，PON活性低于健康对照组（P < 0.0001）。aApo A-I抗体滴度与allDL抗体滴度呈正相关（r = 0.61; P < 0.0001）。PON活性与aApo A-I抗体水平呈负相关（P = 0.0129）。分离来自患者的高滴度抗HDL和aApo A-I抗体，随后与人HDL孵育。这些抗体降低PON活性最高分别为70.2%和78.4%。本研究显示SLE患者存在aHDL和aApo A-I抗体。这些抗体与血浆中PON活性降低相关，体外抑制试验证实了对酶活性的直接抑制。
Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL. Plasma from 55 patients with SLE was collected and IgG aHDL and antiapolipoprotein A-I (aApo A-I) antibodies were assessed by enzyme-linked immunosorbent assay. Standardization of the method was performed in a control population of 150 healthy subjects. Plasma levels above 5 standard deviations of the mean of the control population were considered positive. PON activity was assessed by quantification of p-nitrophenol formation (mu mol/mL/min). Patients with SLE had higher titers of allDL (P < 0.0001) and aApo A-I (P < 0.0001) antibodies, and lower PON activity (P < 0.0001) than healthy controls. There was also a direct correlation between the titers of allDL and aApo A-I antibodies (r = 0.61; P < 0.0001). PON activity was inversely correlated with aApo A-I (P = 0.0129) antibody levels. Anti-HDL and aApo A-I antibodies from patients with high titers were isolated and subsequently incubated with human HDL. These antibodies reduced PON activity up to a maximum of 70.2% and 78.4%, respectively. This study showed the presence of aHDL and aApo A-I antibodies in patients with SLE. These antibodies were associated with reduced PON activity in plasma, and the in vitro inhibition assay confirmed a direct inhibition of the enzyme activity.