Anti-β2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant

Thomas Sailer; Claudia Zoghlami; Christine Kurz; Helmut Rumpold; Peter Quehenberger; Simon Panzer; Ingrid Pabinger

doi:10.1160/TH06-01-0044

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2006; 95(05): 796-801
DOI: 10.1160/TH06-01-0044

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Anti-β2-glycoprotein I antibodies are associated with pregnancy loss in women with the lupus anticoagulant

Autoren

Thomas Sailer

¹Department of Internal Medicine I, Division of Haematology and Haemostaseology
Claudia Zoghlami

¹Department of Internal Medicine I, Division of Haematology and Haemostaseology
Christine Kurz

²Department of Obstetrics and Gynaecology
Helmut Rumpold

³Institute for Medical and Chemical Laboratory Diagnostics
Peter Quehenberger

³Institute for Medical and Chemical Laboratory Diagnostics
Simon Panzer

⁴Clinic for Blood Group Serology, Medical University Vienna, Vienna, Austria
Ingrid Pabinger

¹Department of Internal Medicine I, Division of Haematology and Haemostaseology

Abstract

Summary

The presence of lupus anticoagulant (LA) predisposes to fetal loss and to venous and arterial thrombosis; however, a subgroup of women is unaffected by pregnancy loss. Currently, no predictive markers are available for the identification of women positive for LA at increased risk for pregnancy loss. It was the aim of our study to investigate whether increased anti-β2-GPI-antibodies predict pregnancy loss in women positive for LA. We performed a cross-sectional study in a cohort of 39 women with persistent LA, who had in total 111 pregnancies. Fifteen women had exclusively normal pregnancies (30 pregnancies) and 24 women had pregnancy losses (81 pregnancies). Anti-β2-GPI-antibodies were determined using a semiquantitative enzyme linked immunoassay (QUANTA Lite^™ β2 GPI IgG and IgM; Inova Diagnostics). Increased levels of anti-β2-GPI antibodies were significantly associated with pregnancy loss [odds ratio (OR) 9.6, 95% confidence interval (CI) 1.6 – 56.4].This risk was even higher in the subgroup of women (n=16) with more than two miscarriages or fetal loss after the first trimester [OR 13.1, 95% CI 1.4 – 126.3]. There was no significant association between anticardiolipin antibodies and pregnancy loss [OR 3.5, 95% CI 0.7 – 17.6].The coexistence of anti-β2-GPI and anticardiolipin antibodies was also predictive for pregnancy loss [OR 6.1, 95%CI 1.3 – 29.7]. Interestingly, the prevalence of thrombosis was similar between women with normal pregnancy (87%) and those with pregnancy loss (75%). We conclude that increased levels of anti-β2-GPI antibodies are predictive for pregnancy loss among women positive for LA, and that prophylactic treatment should be considered in these women even without a history of previous pregnancy loss.

Keywords

Lupus anticoagulant - pregnancy loss - anti-β2-glycoproteinI antibodies - anticardiolipin antibodies - antiphospholipid syndrome

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Referenzen

References
1 Lockwood CJ, Romero R, Feinberg RF. et al. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. Am J Obstet Gynecol 1989; 161: 369-73.
2 Perez MC, Wilson WA, Brown HL. et al. Anticardiolipin antibodies in unselected pregnant women. Relationship to fetal outcome. J Perinatol 1991; 11: 33-6.
3 Pattison NS, Chamley LW, McKay EJ. et al. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations. Br J Obstet Gynaecol 1993; 100: 909-13.
4 Rai R, Cohen H, Dave M. et al. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-7.
5 Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002; 100: 408-13.
6 Matsuura E, Igarashi Y, Fujimoto M. et al. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990; 336: 177-8.
7 Galli M, Comfurius P, Maassen C. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-7.
8 Roubey RA, Eisenberg RA, Harper MF. et al. “Anticardiolipin” autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995; 154: 954-60.
9 Chamley LW, Duncalf AM, Mitchell Mdet. al. Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Lancet 1998; 352: 1037-8.
10 Stern C, Chamley L, Hale L. et al. Antibodies to beta2 glycoprotein I are associated with in vitro fertilization implantation failure as well as recurrent miscarriage: results of a prevalence study. Fertil Steril 1998; 70: 938-44.
11 Martinuzzo ME, Forastiero RR, Carreras LO. Anti beta2 glycoproteinI antibodies: detection and association with thrombosis. Br J Haematol 1995; 89: 397-402.
12 Zanon E, Prandoni P, Vianello F. et al. Antibeta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. Thromb Res 1999; 96: 269-74.
13 Zoghlami-Rintelen C, Vormittag R, Sailer T. et al. The presence of IgG antibodies against beta2-glycoproteinI predicts the risk of thrombosis in patients with the lupus anticoagulant. J Thromb Haemost 2005; 3: 1160-5.
14 Pengo V, Biasiolo A, Pegoraro C. et al. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005; 93: 1047-52.
15 De Laat B, Derksen RH, Urbanus RT. et al. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood 2005; 105: 1540-5.
16 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: 1185-90.
17 Wenzel C, Stoiser B, Locker GJ. et al. Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions. Crit Care Med 2002; 30: 763-70.
18 Hsieh K, Knobl P, Rintelen C. et al. Is the determination of anti-beta2 glycoproteinI antibodies useful in patients with venous thromboembolism without the antiphospholipid syndrome?. Br J Haematol 2003; 123: 490-5.
19 Pabinger I, Grafenhofer H, Kyrle PA. et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002; 100: 1060-2.
20 Balestrieri G, Tincani A, Spatola L. et al. Anti-beta 2-glycoproteinI antibodies: a marker of antiphospholipid syndrome?. Lupus 1995; 4: 122-30.
21 Falcon CR, Martinuzzo ME, Forastiero RR. et al. Pregnancy loss and autoantibodies against phospholipid-binding proteins. Obstet Gynecol 1997; 89: 975-80.
22 Forastiero RR, Martinuzzo ME, Cerrato GS. et al. Relationship of anti beta2-glycoproteinI and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies. Thromb Haemost 1997; 78: 1008-14.
23 Katano K, Aoki A, Sasa H. et al. Beta 2-Glycoprotein I-dependent anticardiolipin antibodies as a predictor of adverse pregnancy outcomes in healthy pregnant women. Hum Reprod 1996; 11: 509-12.
24 Aoki K, Matsuura E, Sasa H. et al. Beta2-glycoprotein I-dependent and –independent antibodies in healthy pregnant women. Hum Reprod 1994; 9: 1849-51.
25 Lee RM, Emlen W, Scott JR. et al. Anti-beta2-glycoproteinI antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome. Am J Obstet Gynecol 1999; 181: 642-8.
26 Arnold J, Holmes Z, Pickering W. et al. Anti-beta2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage. Br J Haematol 2001; 113: 911-4.
27 Ailus K, Tulppala M, Palosuo T. et al. Antibodies to beta 2-glycoproteinI and prothrombin in habitual abortion. Fertil Steril 1996; 66: 937-41.
28 Ogasawara M, Aoki K, Matsuura E. et al. Anti beta 2glycoprotein I antibodies and lupus anticoagulant in patients with recurrent pregnancy loss: prevalence and clinical significance. Lupus 1996; 5: 587-92.
29 Miyakis S, Robertson SA, Krillis SA. Beta-2 glycoproteinI and its role in antiphospholipid syndromelessons from knockout mice. Clin Immunol 2004; 112: 136-43.
30 Di Simone N, Meroni PL, de Papa N. et al. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasivness by binding directly and through adhered beta2-glycoprotein I. Arthritis Rheum 2000; 43: 637-42.
31 Robertson SA, Roberts CT, van Beijering E. et al. Effect of beta2-glycoprotein I null mutation on reproductive outcome and antiphospholipid antibody-mediated pregnancy pathology in mice. Mol Hum Reprod 2004; 10: 409-16.
32 Out HJ, Kooijman CD, Bruinse HW. et al. Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies. Eur J Obstet Gynecol Reprod Biol 1991; 41: 179-86.
33 Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 1999; 106: 102-7.
34 Lockshin MD, Druzin ML, Goei S. et al. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med 1985; 313: 152-6.
35 Mousa HA, Alfirevic Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome?. Hum Reprod 2000; 15: 1830-3.
36 De Laat HB, Derksen RH, Urbanus RT. et al. Beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome. Blood 2004; 104: 3598-602.