Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain.
Thromb Haemost. 2017 Nov;117(11):2194-2206. doi: 10.1160/TH17-03-0221. Epub 2017 Nov 30.
The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC ( < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were significant predictors of the impaired PON1 function in SLE ( = -0.143, = 0.045). Conversely, anti-HDL antibodies were associated with higher risk of CVD (odds ratio: 3.69; = 0.012) and lower HDL levels at disease onset ( = -0.324, = 0.044). Finally, anti-PON1 antibodies were associated with carotid IMT in SLE ( = 0.201, = 0.008) and inversely related to cranial arteries blood flow velocities in patients with clinical and subclinical CVD (all < 0.001). In sum, these findings allowed us to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early biomarkers of endothelial damage and premature atherosclerosis in SLE, thus constituting useful therapeutic targets for the prevention of future CVD in these patients.
本研究旨在评估针对高密度脂蛋白（HDL）和对氧磷酶 1（PON1）的 IgG 抗体作为系统性红斑狼疮（SLE）患者心血管疾病（CVD）的潜在生物标志物的可能作用。为此，在 198 名 SLE 患者、100 名健康对照者（HC）和 42 名具有传统心血管危险因素的非自身免疫个体的血清样本中定量了这些自身抗体、PON1 活性和总抗氧化能力。在患者和对照组的亚组中分析了 PON1 rs662 多态性。通过多普勒超声检查了 118 名 SLE 患者和 30 名 HC 的亚临床 CVD，分析颈内动脉、大脑中动脉和基底动脉的内中膜厚度（IMT）和血流参数。与 HC 相比，SLE 患者的抗 HDL 和抗 PON1 抗体血清水平均升高（ < 0.001）；然而，只有抗 PON1 抗体除疾病活动外，还是 SLE 患者 PON1 功能受损的重要预测因子（ = -0.143， = 0.045）。相反，抗 HDL 抗体与 CVD 风险增加相关（比值比：3.69； = 0.012），且在疾病发作时 HDL 水平降低（ = -0.324， = 0.044）。最后，抗 PON1 抗体与 SLE 患者的颈动脉 IMT 相关（ = 0.201， = 0.008），与有临床和亚临床 CVD 患者的颅动脉血流速度呈负相关（均 < 0.001）。总之，这些发现使我们能够提出抗 PON1 和抗 HDL 抗体的血清水平作为 SLE 患者内皮损伤和早发性动脉粥样硬化的潜在早期生物标志物，从而为这些患者未来 CVD 的预防提供有用的治疗靶点。
