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DOI: 10.1160/TH06-10-0604
Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis
A multicenter study with the participation of the European Forum on antiphospholipid antibodiesPublication History
Received
25 October 2006
Accepted after resubmission
01 March 2007
Publication Date:
27 November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200706/lookinside/thumbnails/10-1160-th06-10-0604-1.jpg)
Summary
A multicenter study was set up to evaluate the prevalence, clinical and biological significance of antiphosphatidylethanolamine antibodies (aPE) in thrombotic patients with or without the main known clinical and biological risk factors for thrombosis. APE and antibodies, defined as the laboratory criteria of antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti-beta2-GPI antibodies were measured in 270 patients with thrombosis (234 venous and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic patients compared to 3% of controls (p<0.001) with no predominant isotype, no association with the main known clinical or biological risk factors for thrombosis neither with a type of thrombosis, arterial or venous. In a multivariate logistic regression analysis of antibodies, aPE showed the highest association with thrombosis (odds ratio [OR]: 4.2, p<0.001). Moreover, using a multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE were found to be significantly associated with venous thrombosis (OR:6;p=0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for the APS laboratory criteria. Most of them (21/25) had venous thrombosis, recurrent in ten of them. Four patients also suffered from early or late miscarriages. Our results underline the strength of the association between the presence of aPE and thrombosis and suggest their measurement in thrombotic patients, especially when lupus anticoagulant, anticardiolipin or anti-beta2-GPI antibodies are absent.
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References
- 1 Wilson WA, Gharavi AE, Koike T. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-1311.
- 2 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 2006; 4: 295-306.
- 3 Galli M, Comfurius P, Maassen C. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-1547.
- 4 McNeil HP, Simpson RJ, Chesterman CN. et al. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120-4124.
- 5 Pengo V, Biasolo A, Brocco T. et al. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-rective antibodies. Thromb Haemost 1996; 75: 721-724.
- 6 Hughes GR, Khamashta MA. Seronegative antiphospholipid syndrome. Ann Rheum Dis 2003; 62: 1127.
- 7 Miret C, Cervera R, Reverter JC. et al. Antiphospholipid syndrome without antiphospholipid antibodies at the time of the thrombotic event: transient “seronegative” antiphospholipid syndrome?. Clin Exp Rheumatol 1997; 15: 541-544.
- 8 McIntyre JA, Wagenknecht DR, Faulk WP. Antiphospholipid antibodies: discovery, definitions, detection and disease. Prog Lipid Res 2003; 42: 176-237.
- 9 Karmochkine M, Cacoub P, Piette JC et al. Antiphosphatidylethanolamine antibody as the sole antiphospholipid antibody in systemic lupus erythematosus with thrombosis. Clin Exp Rheumatol 1992; 10: 603-605.
- 10 Karmochkine M, Berard M, Piette JC. et al. Antiphosphatidylethanolamine antibodies in systemic lupus erythematosus. Lupus 1993; 2: 157-160.
- 11 Balada E, Ordi-Ros J, Paredes F. et al. Antiphosphatidylethanolamine antibodies contribute to the diagnosis of antiphospholipid syndrome in patients with systemic lupus erythematosus. Scand J Rheumatol 2001; 30: 235-241.
- 12 Vlachoyiannopoulos PG, Beigbeder G, Dueymes M. et al. Antibodies to phosphatidylethanolamine in antiphospholipid syndrome and systemic lupus erythematosus: their correlation with anticardiolipin antibodies and beta 2 glycoprotein-I plasma levels. Autoimmunity 1993; 16: 245-249.
- 13 Gris JC, Quere I, Sanmarco M. et al. Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nimes Obstetricians and Haematologists Study-NOHA. Thromb Haemost 2000; 84: 228-236.
- 14 Sugi T, Katsunuma J, Izumi S. et al. Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses. Fertil Steril 1999; 71: 1060-1065.
- 15 Sugi T, Matsubayashi H, Inomo A. et al. Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss. J Obstet Gynaecol Res 2004; 30: 326-332.
- 16 Sanmarco M, Alessi MC, Harle JR. et al. Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses. Thromb Haemost 2001; 85: 800-805.
- 17 Verrot D, San-Marco M, Dravet C. et al. Prevalence and signification of antinuclear and anticardiolipin antibodies in patients with epilepsy. Am J Med 1997; 103: 33-37.
- 18 Sanmarco M, Bardin N, Blank M. et al. Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results. Thromb Haemost 2005; 93: 80-87.
- 19 Harris EN, Gharavi AE, Patel SP. et al. Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol 1987; 68: 215-222.
- 20 Brandt JT, Triplett DA, Alving B. et al. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995; 74: 1185-1190.
- 21 Christiansen SC, Cannegieter SC, Koster T. et al. Thrombophilia, clinical factors, and recurrent venous thrombotic events. J Am Med Assoc 2005; 293: 2352-2361.
- 22 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-462.
- 23 Sugi T, McIntyre JA. Certain autoantibodies to phosphatidylethanolamine (aPE) recognize factor XI and prekallikrein independently or in addition to the kininogens. J Autoimmun 2001; 17: 207-214.
- 24 Berard M, Boffa MC. Influence of the phosphatidylethanolamine (PE) and bovine serum origins on anti-PE antibody detection by ELISA. Thromb Res 1997; 85: 439-442.
- 25 Drouvalakis KA, Buchanan RR. Microtitre plate and assay buffer alter detection of antiphosphatidylethanolamine antibodies in lupus anticoagulant positive plasma. Thromb Res 1999; 94: 205-212.
- 26 Wahl DG, Guillemin F, de Maistre E. et al. Metaanalysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis. Lupus 1998; 7: 15-22.
- 27 Galli M, Luciani D, Bertolini G. et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101: 1827-1832.
- 28 Berard M, Chantome R, Marcelli A. et al. Antiphosphatidylethanolamine antibodies as the only antiphospholipid antibodies. I. Association with thrombosis and vascular cutaneous diseases. J Rheumatol 1996; 23: 1369-1374.
- 29 Desauw C, Hachulla E, Boumbar Y. et al. Antiphospholipid syndrome with only antiphosphatidylethanolamine antibodies: report of 20 cases. Rev Med Interne 2002; 23: 357-363.
- 30 Lee EY, Lee CK, Lee TH. et al. Does the antibeta2- glycoprotein I antibody provide additional information in patients with thrombosis?. Thromb Res 2003; 111: 29-32.
- 31 Ebeling F, Pettersson T, Muukkonen L. et al. Beta- 2-glycoprotein I antibodies in patients with thrombosis. Scand J Clin Lab Invest 2003; 63: 111-118.
- 32 Ginsberg JS, Brill-Edwards P, Johnston M. et al. Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study. Blood 1992; 80: 975-980.
- 33 Male C, Foulon D, Hoogendoorn H. et al. Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus. Blood 2005; 106: 4152-4158.