Abstract
目的
探讨氧化型低密度脂蛋白抗体(oxidized low-density lipoprotein antibodies, ox-LDL-Ab)在抗磷脂综合征(antiphospholipid syndrome, APS)中的分布及其临床意义。
方法
共纳入334例患者，包括162例APS患者，122例无血栓或病态妊娠的其他自身免疫性疾病患者作为疾病对照，以及50例健康对照。收集APS患者的临床资料及实验室检查指标，采用酶联免疫吸附试验检测患者的ox-LDL-Ab、IgG/IgA/IgM型抗心磷脂抗体(anticardioli-pin, aCL)、IgG/IgA/IgM型抗β2糖蛋白Ⅰ抗体(anti-β2-glycoprotein Ⅰ, aβ2GPI)。采用统计软件SPSS 27.0分析ox-LDL-Ab与临床及实验室检查指标之间的相关性。
结果
APS组60.5%的患者合并血栓，48.1%的患者出现病态妊娠，34.0%的患者合并血小板减少，aCL、aβ2GPI和狼疮抗凝物(lupus anticoagulant, LAC)的阳性率分别为17.9%、34.6%和46.9%。ox-LDL-Ab在APS患者中的滴度和阳性率显著高于健康对照组[滴度：40.8 (25.4~66.0) U/mL vs. 24.1 (12.3~36.5) U/mL, P=0.001；阳性率：67.3% vs. 36.0%, P=0.001]，与疾病对照组的差异无统计学意义[滴度：40.8 (25.4~66.0) U/mL vs. 35.9 (24.2~53.1) U/mL, P=0.118；阳性率：67.3% vs. 61.5%, P=0.318]。aβ2GPI、aCL、ox-LDL-Ab的曲线下面积分别是0.745 (95%CI: 0.692~0.797)、0.666 (95%CI: 0.608~0.724)、0.609 (95%CI: 0.549~0.669)，约登指数(Youden’s index)分别为0.388、0.269、0.132。ox-LDL-Ab在血清阴性APS中的曲线下面积是0.562 (95%CI: 0.480~0.645)，敏感性和特异性分别为63.9%和47.0%，约登指数为0.109。ox-LDL-Ab阳性组aβ2GPI (42.2% vs. 18.9%, P=0.003)和aCL (22.9% vs. 7.5%, P=0.017)的阳性率高于ox-LDL-Ab阴性组。ox-LDL-Ab与血栓形成、冠心病、病态妊娠、高脂血症、低补体血症及LAC阳性率无相关性。
结论
ox-LDL-Ab与aCL、aβ2GPI有一定相关性，但与血栓、病态妊娠及冠心病不相关。
Keywords: 氧化型低密度脂蛋白抗体, 抗磷脂综合征, 血栓形成, 抗磷脂抗体
Abstract
Objective
To investigate the significance and distribution of oxidized low-density lipoprotein antibodies (ox-LDL-Ab) in patients with antiphospholipid syndrome (APS).
Methods
In this study, 334 patients who were hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital were included. There were 162 APS patients, 122 patients with other autoimmune diseases without thrombosis or obstetric disease as disease control and 50 healthy controls. The clinical data and laboratory indicators were retrospectively collected. The ox-LDL-Ab, anticardiolipin (aCL) IgG/IgA/IgM, and anti-β2-glycoprotein Ⅰ (aβ2GPI) IgG/IgA/IgM were detected by enzyme-linked immunosorbent assay (ELISA). The relationship between ox-LDL-Ab and clinical and laboratory parameters were analyzed by SPSS 27.0.
Results
In APS group, 60.5% of patients had thrombosis, 48.1% had pregnancy morbidity, 34.0% had thrombocytopenia. The positive rates of aCL, aβ2GPI and lupus anticoagulant (LAC) were 17.9%, 34.6%, and 46.9%, respectively. The ox-LDL-Ab titers and positive rate in APS group were higher than that in healthy controls [titers: 40.8 (25.4-66.0) U/mL vs. 24.1 (12.3-36.5) U/mL, P=0.001; positive rate: 67.3% vs. 36.0%, P=0.001]. The diffe-rences in titers and positive rate of ox-LDL-Ab between APS patients and disease controls were not statistically significant [titers: 40.8 (25.4-66.0) U/mL vs. 35.9 (24.2-53.1) U/mL, P=0.118; positive rate: 67.3% vs. 61.5%, P=0.318]. The area under curve (AUC) for aβ2GPI, aCL, and ox-LDL-Ab were 0.745 (95%CI: 0.692-0.797), 0.666 (95%CI: 0.608-0.724), 0.609 (95%CI: 0.549-0.669), respectively. The Youden's index was 0.388, 0.269, and 0.132, respectively. The AUC for ox-LDL-Ab in seronegative APS patients was 0.562 (95%CI: 0.480-0.645). The sensitivity and specificity of ox-LDL-Ab in seronegative APS patients were 63.9% and 47.0%, respectively, and the Youden's index was 0.109. The ox-LDL-Ab positive group had higher positive rate of aβ2GPI (42.2% vs. 18.9%, P=0.003) and aCL (22.9% vs. 7.5%, P=0.017) than the ox-LDL-Ab negative group. There was no correlation between ox-LDL-Ab and thrombosis, coronary artery disease, pregnancy morbidity, hyperlipidemia, hypocomplementemia, and LAC positivity.
Conclusion
Ox-LDL-Ab was correlated with aCL and aβ2GPI, and no association were observed between ox-LDL-Ab and thrombosis, coronary artery disease, and pregnancy morbidity.
Keywords: Oxidized low-density lipoprotein antibodies, Antiphospholipid syndrome, Thrombosis, Antiphospholipid antibodies
抗磷脂综合征(antiphospholipid syndrome, APS)是一种以血栓形成、病态妊娠和血小板减少等为主要临床表现的自身免疫性疾病，其特征性实验室检查表现是抗磷脂抗体(antiphospholipid anti-body, aPL)的存在。aPL是一组能够识别并结合血小板和内皮细胞膜上磷脂结合蛋白的自身抗体，主要由狼疮抗凝物(lupus anticoagulant, LAC)、抗心磷脂抗体(anticardiolipin, aCL)和抗β2糖蛋白Ⅰ(anti-β2-glycoprotein Ⅰ, aβ2GPI)抗体组成[1]。近年来，越来越多的“标准外”临床表现和抗磷脂抗体被发现和提出，临床将高度怀疑患有APS但aPL持续阴性的患者定义为“血清阴性APS”(seronegative APS, SNAPS)[2]。许多学者提出，应该对APS诊断标准进行修改以提高诊断的敏感性[3]。
氧化型低密度脂蛋白(oxidized low-density lipoproteins, ox-LDL)由血清中低密度脂蛋白氧化修饰而成，是参与动脉粥样硬化的关键抗原之一[4]。ox-LDL可以诱导机体发生特异性免疫反应形成氧化型低密度脂蛋白抗体(oxidized low-density lipoprotein antibodies, ox-LDL-Ab)[5-6]。低密度脂蛋白包含磷脂、磷脂结合蛋白和载脂蛋白B，因此，ox-LDL-Ab也被认为是磷脂抗体的一种[7]。除APS外，ox-LDL-Ab也可见于糖尿病、动脉粥样硬化和心肌梗死[6, 8-9]。既往研究显示，APS患者ox-LDL/β2GPI抗体滴度显著高于非APS患者，并且动脉血栓患者的滴度显著高于静脉血栓及病态妊娠的患者，提示ox-LDL/β2GPI抗体的存在可能与APS患者动脉粥样硬化的发生相关[10]。然而，目前ox-LDL-Ab在APS中的研究相对较少，并且其在APS中的临床意义仍然存在争论[11-12]。
本研究检测APS患者中ox-LDL-Ab的分布情况及其与临床症状、实验室检测指标的相关性，着重分析ox-LDL-Ab与冠心病的关系，以期明确ox-LDL-Ab在APS中的临床意义。
1. 资料与方法
1.1. 研究资料
本研究连续选取2008年1月至2017年10月在北京大学人民医院风湿免疫科接受诊治的、国际疾病分类标准(第9版/第10版) (International Classification of Diseases，9th/10th, ICD-9/10)编码为“抗磷脂综合征”的162例APS患者，同时选取122例无血栓形成或病态妊娠的其他自身免疫性疾病患者作为疾病对照组，以及50例健康对照组。所有入组APS的患者均符合2006年的悉尼标准并且至少由两名风湿病专家确认[13]。排除标准：(1)遗传性和其他获得性易栓症患者；(2)临床及实验室资料不齐全的患者。
疾病对照组包括42例系统性红斑狼疮(syste-mic lupus erythematosus, SLE)患者、26例干燥综合征(Sjögren’s syndrome, SS)患者、20例骨关节炎患者(osteoarthritis, OA)、17例类风湿关节炎(rheumatoid arthritis, RA)患者和17例强直性脊柱炎(ankylosing spondylitis, AS)患者。疾病对照组的所有患者均符合各自疾病现行的分类标准。
所有纳入的患者均签署知情同意书，本研究经北京大学人民医院医学伦理委员会批准(2019PHB253)。
1.2. 方法
从北京大学人民医院临床数据中心提取上述患者的病历资料，包括年龄、性别等一般资料，临床资料及实验室检查指标。临床资料包括病态妊娠、血栓形成、冠心病、网状青斑和血小板减少。病态妊娠包括：(1)≥10周的形态学正常的死胎；(2)妊娠34周之前因子痫、子痫前期或胎盘功能不全所致的早产；(3)妊娠10周以前连续发生3次及以上自发性流产[13]。血栓形成包括动脉血栓形成(包括脑梗死、心肌梗死等)、静脉血栓形成(包括肺栓塞、下肢深静脉血栓、肾静脉血栓、门脉血栓等)及微血管血栓形成[13]。实验室检查指标包括血常规、补体C3(complement 3)、补体C4(complement 4)、aPL、血总胆固醇(total cholesterol, TCHO)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)及高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)。
入组患者采静脉血3 mL至黄色血清分离胶-促凝管中，离心后取上清液，-80 ℃冻存。采用酶联免疫吸附试验(enzyme-linked immunosorbent assay，ELISA)检测患者血液样本中的ox-LDL-Ab、IgG/IgA/IgM型aCL、IgG/IgA/IgM型aβ2GPI。ox-LDL-Ab、aCL及aβ2GPI检测试剂盒均来自德国HUMAN公司，严格按照产品说明书进行操作：(1)在各反应孔中分别加入稀释的标本、质控血清和系列标准品，空白孔加缓冲液，室温下孵育1 h后洗涤3次；(2)所有反应孔均加入酶标抗体，室温孵育30 min，再洗涤3次；(3)每孔均加入底物，室温避光保存10 min；(4)每孔加终止液终止反应，在450 nm波长下检测吸收值。参考试剂盒说明书，ox-LDL-Ab浓度高于30 U/mL为阳性，aCL IgG/IgA/IgM浓度高于45 U/mL为阳性，aβ2GPI IgG/IgA/IgM浓度高于5 U/mL为阳性。
1.3. 统计学分析
采用统计软件SPSS 27.0对数据进行分析。非连续变量采用百分数表示，使用Shapiro-Wilk检验进行连续变量的正态性检验，符合正态分布的连续变量使用均数±标准差表示，两组间比较采用t检验，不符合正态分布的连续变量使用中位数(四分位距)表示，采用Mann-Whitney U检验。使用Kruskal-Wallis检验和Mann-Whitney U检验比较APS组、疾病对照组和健康对照组抗体滴度的差异，使用方差分析和卡方检验比较APS组、疾病对照组和健康对照组抗体阳性率的差异，使用卡方检验比较ox-LDL-Ab阳性和阴性的APS患者中临床和实验室特征的差异，采用受试者工作特征曲线(receiver ope-rating characteristic curve, ROC)评估ox-LDL-Ab对APS的诊断价值。P < 0.05为差异有统计学意义。
2. 结果
2.1. 一般资料
本研究纳入162例APS患者，包括男性19例，女性143例，男、女性别比例为1.0 ∶7.5，平均年龄为(41.7±15.2)岁，其中，60.5%的患者合并血栓，48.1%的患者出现病态妊娠，34.0%的患者合并血小板减少。aCL、aβ2GPI和LAC的阳性率分别为17.9%、34.6%和46.9%(表 1)。
表 1.
APS患者、疾病对照组和健康对照组的临床基本资料
Demographics characteristics of APS patients, disease controls, and healthy controls
| Parameters | APS patients (n=162) | Disease controls (n=122) | Healthy controls (n=50) |
| Data are presented as x±s or n (%). * three classic antibodies in the patient’s serum including the aCL, aβ2GPI, and LAC were all negative during test. APS, antiphospholipid syndrome; CAD, coronary artery disease; aCL, anticardiolipin antibodies; aβ2GPI, anti-β2-glycoprotein Ⅰ anti-bodies; LAC, lupus anticoagulant; aPLs, antiphospholipid antibodies; ox-LDL-Ab, oxidized low-density lipoprotein antibodies. | |||
| Age/years | 41.7±15.2 | 48.8±16.6 | 42.4±10.3 |
| Gender (female) | 143 (88.3) | 106 (86.9) | 33 (66.0) |
| Thrombosis | 98 (60.5) | 0 (0) | 0 (0) |
| Venous thrombosis | 61 (37.7) | 0 (0) | 0 (0) |
| Deep venous thrombosis | 40 (24.7) | 0 (0) | 0 (0) |
| Pulmonary embolism | 19 (11.7) | 0 (0) | 0 (0) |
| Arterial thrombosis | 56 (34.6) | 0 (0) | 0 (0) |
| Cerebral infarction | 35 (21.6) | 0 (0) | 0 (0) |
| CAD | 8 (4.9) | 0 (0) | 0 (0) |
| Atherosclerosis | 47 (29.0) | 0 (0) | 0 (0) |
| Both venous and arterial thrombosis | 19 (11.7) | 0 (0) | 0 (0) |
| Pregnancy morbidity | 78 (48.1) | 0 (0) | 0 (0) |
| Both thrombosis and pregnancy morbidity | 14 (8.6) | 0 (0) | 0 (0) |
| Livedo reticularis | 1 (0.6) | 0 (0) | 0 (0) |
| Thrombocytopenia | 55 (34.0) | 0 (0) | 0 (0) |
| aCL IgG/IgA/IgM (+) | 29 (17.9) | 0 (0) | 0 (0) |
| aβ2GPI IgG/IgA/IgM (+) | 56 (34.6) | 2 (1.6) | 1 (2.0) |
| LAC (+) | 76 (46.9) | 8 (6.6) | 0 (0) |
| Double positive aPLs | 29 (17.9) | 0 (0) | 0 (0) |
| Triple positive aPLs | 34 (21.0) | 0 (0) | 0 (0) |
| Triple negative aPLs* | 42 (25.9) | 111 (91.0) | 49 (98.0) |
| ox-LDL-Ab (+) | 109 (67.3) | 75 (61.5) | 18 (36.0) |
疾病对照组和健康对照组的基本资料、aPL分布情况如表 1所示。ox-LDL-Ab在APS组和对照组的滴度及阳性率如图 1所示。ox-LDL-Ab在APS患者中的滴度和阳性率显著高于健康对照组[滴度：40.8 (25.4~66.0) U/mL vs. 24.1 (12.3~36.5) U/mL, P=0.001；阳性率：67.3% vs. 36.0%, P=0.001]，与疾病对照组的差异无统计学意义[滴度：40.8 (25.4~66.0) U/mL vs. 35.9 (24.2~53.1) U/mL, P=0.118；阳性率：67.3% vs. 61.5%, P=0.318]。
图 1.
ox-LDL-Ab在APS患者、疾病对照组和健康对照组的滴度及阳性率
Titers and positive rate of ox-LDL-Ab in APS patients, disease controls, and healthy controls
A, titers; B, positive rate. ox-LDL-Ab, oxidized low-density lipoprotein antibodies; APS, antiphospholipid syndrome; DC, disease controls; HC, healthy controls.
2.2. ox-LDL-Ab与APS患者临床指标的相关性
ox-LDL-Ab阳性组的aβ2GPI阳性率(42.2% vs. 18.9%, P=0.003)和aCL阳性率(22.9% vs. 7.5%, P=0.017)显著高于ox-LDL-Ab阴性组。ox-LDL-Ab阳性和阴性的APS患者中，血栓形成、病态妊娠、冠心病、LAC阳性率、高脂血症和低补体血症的比例差异无统计学意义(表 2)。
表 2.
APS患者中ox-LDL-Ab与临床症状及实验室指标的关系
The relationship between ox-LDL-Ab and clinical symptoms and laboratory parameters in APS patients
| Parameters | ox-LDL-Ab (+)(n=109), n (%) | ox-LDL-Ab (-)(n=53), n (%) | P value |
| * statistical total population was 142 female patients. # statistical total population was 130 patients. △ statistical total population was 129 patients. LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TCHO, total cholesterol; other abbreviations as in Table 1. Hyper-LDL-C, LDL-C ≥ 4.10 mmol/L; Hypo-HDL-C, HDL-C < 1.03 mmol/L; Hyper-TCHO, TCHO ≥ 6.20 mmol/L; Hypocomplementemia, C3 levels < 0.9 g/L and/or C4 levels < 0.1 g/L. | |||
| Thrombosis | 65 (59.6) | 33 (62.3) | 0.748 |
| Arterial thrombosis | 37 (33.9) | 19 (35.8) | 0.811 |
| Venous thrombosis | 42 (38.5) | 19 (35.8) | 0.741 |
| Pulmonary embolism | 12 (11.0) | 7 (13.2) | 0.683 |
| Cerebral infarction | 22 (20.2) | 13 (24.5) | 0.548 |
| CAD | 5 (4.6) | 3 (5.7) | 0.719 |
| Pregnancy morbidity* | 54 (55.1) | 24 (53.3) | 0.844 |
| Neuropsychiatric symptoms | 8 (7.3) | 7 (13.2) | 0.254 |
| Hyperlipidemia | 36 (33.0) | 14 (26.4) | 0.393 |
| Hyper-LDL-C# | 7 (8.1) | 4 (9.1) | >0.999 |
| Hypo-HDL-C# | 35 (40.2) | 18 (40.9) | 0.940 |
| Hyper-TCHO# | 4 (4.5) | 3 (6.7) | 0.604 |
| aβ2GPI IgG/IgA/IgM (+) | 46 (42.2) | 10 (18.9) | 0.003 |
| aCL IgG/IgA/IgM (+) | 25 (22.9) | 4 (7.5) | 0.017 |
| LAC (+) | 50 (45.9) | 26 (49.1) | 0.703 |
| Thrombocytopenia | 35 (32.1) | 20 (37.7) | 0.478 |
| Hypocomplementemia△ | 36 (42.4) | 20 (45.5) | 0.736 |
2.3. ox-LDL-Ab对APS的诊断价值
为了进一步评估ox-LDL-Ab对APS的预测价值，绘制ROC曲线。aβ2GPI、aCL、ox-LDL-Ab的曲线下面积分别是0.745 (95%CI: 0.692~0.797)、0.666 (95%CI: 0.608~0.724)、0.609 (95%CI: 0.549~0.669)，约登指数(Youden’s index)分别为0.388、0.269、0.132 (表 3，图 2)。
表 3.
ox-LDL-Ab对APS的诊断价值
Diagnostic value of ox-LDL-Ab for APS
| Parameters | AUC | 95%CI | Sensitivity | Specificity | Youden’s index |
| Abbreviations as in Table 1. AUC, area under curve. | |||||
| aβ2GPI | 0.745 | 0.692-0.797 | 0.475 | 0.913 | 0.388 |
| aCL | 0.666 | 0.608-0.724 | 0.519 | 0.750 | 0.269 |
| ox-LDL-Ab | 0.609 | 0.549-0.669 | 0.673 | 0.459 | 0.132 |
图 2.
ox-LDL-Ab在APS中的ROC曲线
ROC curve of ox-LDL-Ab in APS
ROC, receiver operating characteristic curve; other abbreviations as in Table 1.
ox-LDL-Ab在aCL阴性、aβ2GPI阴性、aCL和aβ2GPI均阴性、aCL和LAC均阴性、aβ2GPI和LAC均阴性的APS患者中的约登指数分别为0.094、0.061、0.048、0.115、0.123。ox-LDL-Ab在血清阴性APS中的曲线下面积是0.562 (95%CI: 0.480~0.645)，敏感性和特异性分别为63.9%和47.0%，约登指数为0.109(表 4)。
表 4.
ox-LDL-Ab在aPL抗体阴性患者中的敏感性和特异性
Sensitivity and specificity of ox-LDL-Ab in patients with negative aPL antibodies
| Negative antibody | Sensitivity | Specificity | Youden’s index |
| Abbreviations as in Table 1. | |||
| aCL | 0.632 | 0.462 | 0.094 |
| aβ2GPI | 0.594 | 0.467 | 0.061 |
| aCL+aβ2GPI | 0.578 | 0.470 | 0.048 |
| aCL+LAC | 0.653 | 0.462 | 0.115 |
| aβ2GPI+LAC | 0.656 | 0.467 | 0.123 |
| LAC+aCL+aβ2GPI | 0.639 | 0.470 | 0.109 |
3. 讨论
本研究发现ox-LDL-Ab对APS的诊断能力不如aCL和aβ2GPI，ox-LDL-Ab阳性组的aβ2GPI和aCL阳性率显著高于ox-LDL-Ab阴性组。本研究未发现ox-LDL-Ab与血栓形成、病态妊娠、冠心病、高脂血症、低补体血症、血小板减少及LAC阳性率之间的相关性。ox-LDL-Ab在3个标准磷脂抗体均阴性时的敏感性和特异性分别为63.9%和47.0%，约登指数为0.109，因此ox-LDL-Ab未体现出其在血清阴性APS中的诊断价值。
ox-LDL是人体脂蛋白中造成动脉损伤最有效的成分。ox-LDL和LDL衍生的氧化磷脂可影响巨噬细胞功能，激活血管平滑肌细胞和附近其他细胞的炎症反应，促进泡沫细胞形成，此外，它们还能够提供可以被C反应蛋白、补体系统和IgM识别的氧化特异性表位[14-15]。ox-LDL可以促进单核巨噬细胞在局部病变中的迁移，促进泡沫细胞的形成；另外，ox-LDL可增加血液黏滞度，直接损伤血管内皮细胞，最终加速动脉粥样硬化斑块的形成[16]。有研究表明，ox-LDL对血小板功能也有影响，研究发现高脂血症患者体内的血小板处于高活性状态，比正常血小板更容易活化聚集[17]。ox-LDL还具有很强的免疫原性，可诱导ox-LDL-Ab的形成。由于ox-LDL和ox-LDL-Ab与动脉粥样硬化关系密切，其作为血管病变的预测作用也越发受到重视。尽管多项研究表明ox-LDL在动脉粥样硬化的发病机制中发挥了作用，但关于ox-LDL、ox-LDL-Ab与动脉粥样硬化性心血管疾病之间的关系仍然存在争论。Strobel等[18]回顾了26项ox-LDL-Ab与心血管疾病的研究，其中有16项研究显示ox-LDL-Ab可预测心血管事件，而有10项研究未发现二者的阳性关系。本研究着重分析了ox-LDL-Ab与冠状动脉疾病之间的关系，并未发现二者之间的相关性，为进一步探索ox-LDL-Ab的预测价值，仍需要大样本的多中心研究进一步验证。
既往关于ox-LDL-Ab与APS的研究较少。本研究发现，ox-LDL-Ab对APS的预测能力不如aβ2GPI和aCL，并且其与APS患者是否合并血栓形成、病态妊娠、冠状动脉疾病不相关，这可能是由于多种因素参与了APS患者血栓事件的形成。有一项荟萃分析显示，aβ2GPI与血栓形成弱相关[19]。本研究中，ox-LDL-Ab的阳性率与患者的血脂水平不相关，可能提示ox-LDL-Ab参与动脉粥样硬化的机制与高脂血症关系不大。
本研究发现，ox-LDL-Ab阳性组的aβ2GPI和aCL阳性率高于抗体阴性组。既往研究也发现，ox-LDL-Ab的滴度与aCL及aβ2GPI的滴度相关[20]。APS患者血清中可以检测到ox-LDL/β2GPI复合物，ox-LDL能够与β2GPI结合形成稳定的、比单独ox-LDL更危险的致动脉粥样硬化的复合物，ox-LDL/β2GPI复合物和复合物抗体的存在提示其在血管损伤、氧化应激以及在自身免疫介导的动脉粥样硬化血栓形成中的积极作用[21-22]，所以我们推测，ox-LDL-Ab阳性组的aβ2GPI阳性率较高与上述复合物的形成相关。本研究发现ox-LDL-Ab阳性组aCL阳性率高，可能与aCL阳性患者体内较高的氧化应激状态相关。白玲等[23]的研究发现，aCL阳性的冠心病患者ox-LDL水平高于aCL阴性患者，与本研究结果有相似之处。
本研究的局限之处在于只是测量了单一时间点的ox-LDL-Ab表达情况，并不能反映ox-LDL与APS发生、发展的时间相关性；另外，本研究的样本量相对较少，但162例已能够初步反映ox-LDL-Ab与APS的相关性，为后续的研究奠定了一定基础。
综上所述，ox-LDL-Ab与aCL、aβ2GPI有一定的相关性，与血栓事件、病态妊娠、冠心病无相关性。
Funding Statement
中华国际医学交流基金会基金(Z-2018-40-2101)
Supported by the China International Medical Foundation (Z-2018-40-2101)
Contributor Information
李 春 (Chun LI), Email: 13811190098@163.com.
张 学武 (Xue-wu ZHANG), Email: xuewulore@163.com.
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