氧化型低密度脂蛋白抗体在抗磷脂综合征中的临床意义

Clinical significance of oxidized low-density lipoprotein antibody in antiphospholipid syndrome

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-glycoproteinⅠ,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。

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-glycoproteinⅠ(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.