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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (6): 1117-1122. doi: 10.19723/j.issn.1671-167X.2022.06.010

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

Yu-ke HOU,Qing-meng CAI,Xiang-jun LIU,Ze-lin YUN,Chun LI*(),Xue-wu ZHANG*()   

  1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
  • Received:2022-08-22 Online:2022-12-18 Published:2022-12-19
  • Contact: Chun LI,Xue-wu ZHANG E-mail:13811190098@163.com;xuewulore@163.com
  • Supported by:
    the China International Medical Foundation(Z-2018-40-2101)

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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.

Key words: Oxidized low-density lipoprotein antibodies, Antiphospholipid syndrome, Thrombosis, Antiphospholipid antibodies

CLC Number: 

  • R593.2

Table 1

Demographics characteristics of APS patients, disease controls, and healthy controls"

Parameters APS patients (n=162) Disease controls (n=122) Healthy controls (n=50)
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)

Figure 1

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."

Table 2

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
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

Table 3

Diagnostic value of ox-LDL-Ab for APS"

Parameters AUC 95%CI Sensitivity Specificity Youden’s index
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

Figure 2

ROC curve of ox-LDL-Ab in APS ROC, receiver operating characteristic curve; other abbreviations as in Table 1."

Table 4

Sensitivity and specificity of ox-LDL-Ab in patients with negative aPL antibodies"

Negative antibody Sensitivity Specificity Youden’s index
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
1 Devreese KMJ , Ortel TL , Pengo V , et al. Laboratory criteria for antiphospholipid syndrome: Communication from the SSC of the ISTH[J]. J Thromb Haemost, 2018, 16 (4): 809- 813.
doi: 10.1111/jth.13976
2 Conti F , Andreoli L , Crisafulli F , et al. Does seronegative obstetric APS exist? "pro" and "cons"[J]. Autoimmun Rev, 2019, 18 (12): 102407.
doi: 10.1016/j.autrev.2019.102407
3 Abreu MM , Danowski A , Wahl DG , et al. The relevance of "non-criteria" clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Anti-bodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features[J]. Autoimmun Rev, 2015, 14 (5): 401- 414.
doi: 10.1016/j.autrev.2015.01.002
4 Hulthe J . Antibodies to oxidized LDL in atherosclerosis development: Clinical and animal studies[J]. Clin Chim Acta, 2004, 348 (1/2): 1- 8.
5 Steinberg D . Low density lipoprotein oxidation and its pathobio-logical significance[J]. J Biol Chem, 1997, 272 (34): 20963- 20966.
doi: 10.1074/jbc.272.34.20963
6 Salonen JT , Ylä-Herttuala S , Yamamoto R , et al. Autoantibody against oxidised LDL and progression of carotid atherosclerosis[J]. Lancet, 1992, 339 (8798): 883- 887.
doi: 10.1016/0140-6736(92)90926-T
7 Vaarala O . Antiphospholipid antibodies and atherosclerosis[J]. Lupus, 1996, 5 (5): 442- 447.
doi: 10.1177/096120339600500522
8 Ryan M , Owens D , Kilbride B , et al. Antibodies to oxidized lipoproteins and their relationship to myocardial infarction[J]. QJM, 1998, 91 (6): 411- 415.
doi: 10.1093/qjmed/91.6.411
9 Bellomo G , Maggi E , Poli M , et al. Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM[J]. Diabetes, 1995, 44 (1): 60- 66.
doi: 10.2337/diab.44.1.60
10 Lopez D , Kobayashi K , Merrill JT , et al. IgG autoantibodies against beta2-glycoprotein Ⅰ complexed with a lipid ligand derived from oxidized low-density lipoprotein are associated with arterial thrombosis in antiphospholipid syndrome[J]. Clin Dev Immunol, 2003, 10 (2/3/4): 203- 211.
11 Romero FI , Amengual O , Atsumi T , et al. Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein Ⅰ antibodies but not with antibodies against oxidized low-density lipoprotein[J]. Br J Rheumatol, 1998, 37 (8): 883- 888.
doi: 10.1093/rheumatology/37.8.883
12 Bec'arevic' M , Andrejevic' S , Miljic' P , et al. Serum lipids and anti-oxidized LDL antibodies in primary antiphospholipid syndrome[J]. Clin Exp Rheumatol, 2007, 25 (3): 361- 366.
13 Miyakis S , Lockshin MD , Atsumi T , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)[J]. J Thromb Haemost, 2006, 4 (2): 295- 306.
doi: 10.1111/j.1538-7836.2006.01753.x
14 Rezende L , Couto NFD , Fernandes-Braga W , et al. OxLDL induces membrane structure rearrangement leading to biomechanics alteration and migration deficiency in macrophage[J]. Biochim Biophys Acta Biomembr, 2022, 1864 (9): 183951.
doi: 10.1016/j.bbamem.2022.183951
15 Hartley A , Haskard D , Khamis R . Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis: Novel insights and future directions in diagnosis and therapy[J]. Trends Cardiovasc Med, 2019, 29 (1): 22- 26.
doi: 10.1016/j.tcm.2018.05.010
16 Itakura H , Yokoyama M , Matsuzaki M , et al. Relationships between plasma fatty acid composition and coronary artery disease[J]. J Atheroscler Thromb, 2011, 18 (2): 99- 107.
doi: 10.5551/jat.5876
17 Yang SH , Li YT , Du DY . Oxidized low-density lipoprotein-induced CD147 expression and its inhibition by high-density lipoprotein on platelets in vitro[J]. Thromb Res, 2013, 132 (6): 702- 711.
doi: 10.1016/j.thromres.2013.10.003
18 Strobel NA , Fassett RG , Marsh SA , et al. Oxidative stress biomarkers as predictors of cardiovascular disease[J]. Int J Cardiol, 2011, 147 (2): 191- 201.
doi: 10.1016/j.ijcard.2010.08.008
19 Jiang D , Lim W , Crowther M , et al. A systematic review of the association between anti-beta-2 glycoprotein Ⅰ antibodies and APS manifestations[J]. Blood Adv, 2021, 5 (20): 3931- 3936.
doi: 10.1182/bloodadvances.2021005205
20 Hayem G , Nicaise-Roland P , Palazzo E , et al. Anti-oxidized low-density-lipoprotein (OxLDL) antibodies in systemic lupus erythematosus with and without antiphospholipid syndrome[J]. Lupus, 2001, 10 (5): 346- 351.
doi: 10.1191/096120301667475689
21 Li J , Chi Y , Liu S , et al. Recombinant domain V of β2-glycoprotein Ⅰ inhibits the formation of atherogenic oxLDL/β2-glycoprotein Ⅰ complexes[J]. J Clin Immunol, 2014, 34 (6): 669- 676.
22 Matsuura E , Lopez LR . Autoimmune-mediated atherothrombosis[J]. Lupus, 2008, 17 (10): 878- 887.
23 白玲, 谭雪峰, 刘平. 冠心病患者抗心磷脂抗体与PON、ox-LDL、MDA和SOD的相关性[J]. 心脏杂志, 2014, 26 (4): 453- 455.
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