Anti-β2 Glycoprotein I Antibodies and Platelet Activation in Patients with Antiphospholipid Antibodies: Association with Increased Excretion of Platelet-Derived Thromboxane Urinary Metabolites

Ricardo Forastiero; Marta Martinuzzo; Luis O. Carreras; Jacques Maclouf

doi:10.1055/s-0037-1614216

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(01): 42-45
DOI: 10.1055/s-0037-1614216

Review Article

Schattauer GmbH

Anti-β₂ Glycoprotein I Antibodies and Platelet Activation in Patients with Antiphospholipid Antibodies: Association with Increased Excretion of Platelet-Derived Thromboxane Urinary Metabolites

Authors

Ricardo Forastiero

¹From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
Marta Martinuzzo

¹From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
Luis O. Carreras

¹From the University Institute of Biomedical Sciences, Favaloro Foundation, Buenos Aires, Argentina
Jacques Maclouf

¹From the IFR Circulation-Lariboisière, U348 INSERM, Paris, France

Abstract

Summary

Platelet activation may contribute to the increased risk of thrombotic complications in patients with antiphospholipid antibodies (aPL). The increased urinary excretion of 11-dehydro-thromboxane B₂ (11-DH-TXB₂) reported in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (aCL) reflects in vivo platelet activation. However the majority of autoimmune aPL are directed to β₂ glycoprotein I (β₂GPI) or prothrombin (II). We investigated the relationship of these antibodies with 11-DH-TXB₂ urinary excretion in 34 patients with aPL. The urinary 11-DH-TXB₂ was measured by EIA after extraction on octadecyl columns and purification on silica gel columns, which was validated by thin-layer chromatography/EIA procedure. A significantly increased excretion of 11-DH-TXB₂ was found in aPL patients as compared to 18 normal controls (p <0.01). But no differences were seen in the excretion of 11-DH-TXB₂ between patients with or without LA, or aCL. The number of patients with anti-II antibodies was too small to draw any conclusion. In contrast, patients with anti-β₂GPI antibodies IgG at moderate/high titre (group A, n = 14) had higher levels of urinary 11-DH-TXB₂ than those at low titre or negative (group B, n = 20) (p = 0.01). The group A of patients presented an increase in 11-DH-TXB₂ compared to controls (p <0.001), but no statistically significant difference was found between patients from the group B and normal controls. A correlation between levels of urinary 11-DH-TXB₂ and titre of antibodies was only found for anti-β₂GPI-IgG (r_s = 0.51, p <0.005). Our data show that the observed platelet activation in aPL patients is related to the presence of antibodies reacting with β₂GPI.

Full Text

References

References
1 Harris EN. The antiphospholipid syndrome – an introduction.. In: Phospholipid-Binding Antibodies.. Harris EN, Exner T, Hughes GRV, Asherson RA. eds. Boca Raton, Florida (USA): CRC Press; 1991: 373-86.
2 Carreras LO, Forastiero RR. Pathogenic role of antiprotein-phospholipid antibodies.. Haemostasis 1996; 26: 340-57.
3 Carreras LO, Defreyn G, Machin SJ, Vermylen J, Deman R, Spitz B, Van Assche A. Recurrent arterial thrombosis, repeated intrauterine death and »lupus« anticoagulant. Detection of an immunoglobulin interfering with prostacyclin formation.. Lancet 1981; 1: 244-6.
4 Schörer AE, Wickham NWR, Watson KV. Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation.. Br J Haematol 1989; 71: 399-407.
5 Watson KV, Schörer AE. Lupus anticoagulant inhibition of in vitro prostacyclin release is associated with a thrombosis-prone subset of patients.. Am J Med 1991; 90: 47-53.
6 Martinuzzo ME, Maclouf J, Carreras LO, Lévy Toledano S. Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation.. Thromb Haemost 1993; 70: 667-71.
7 Catella F, FitzGerald GA. Paired analysis of urine thromboxane B₂ metabolites in humans.. Thromb Res 1987; 47: 647-56.
8 Arfors L, Vesterqvist O, Johnsson H, Gréen K. Increased thromboxane formation in patients with antiphospholipid syndrome.. Eur J Clin Invest 1990; 20: 607-12.
9 Lellouche F, Martinuzzo M, Said P, Maclouf J, Carreras LO. Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant.. Blood 1991; 78: 2894-9.
10 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van BredaVriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor.. Lancet 1990; 335: 1544-7.
11 McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Antiphospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β₂-glycoprotein I (apolipoprotein H).. Proc Natl Acad Sci USA 1990; 87: 4120-4.
12 Arvieux J, Darnige L, Caron C, Reber G, Bensa JC, Colomb MG. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants.. Thromb Haemost 1995; 74: 1120-5.
13 Martinuzzo ME, Forastiero RR, Carreras LO. Anti β₂-glycoprotein I: Detection and association with thrombosis.. Br J Haematol 1995; 89: 397-402.
14 Viard JP, Amoura Z, Bach JF. Association of anti β₂-glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus.. Am J Med 1992; 93: 181-6.
15 Forastiero RR, Martinuzzo ME, Cerrato GS, Kordich LC, Carreras LO. Relationship of anti β₂-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies.. Thromb Haemost 1997; 78: 1008-15.
16 Pengo V, Biasiolo A, Brocco T, Tonetto S, Ruffatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies.. Thromb Haemost 1996; 75: 721-4.
17 Vaarala O, Puurunen M, Mänttäri M, Manninen V, Aho K, Palosuo T. Antibodies to prothrombin imply a risk of myocardial infarction in middle-aged men.. Thromb Haemost 1996; 75: 456-9.
18 Forastiero RR, Cerrato GS, Carreras LO. Evaluation of recently described tests for detection of the lupus anticoagulant.. Thromb Haemost 1994; 72: 728-33.
19 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: An update.. Thromb Haemost 1995; 74: 1185-90.
20 Harris EN. The Second International Anticardiolipin Standardization Workshop/The Kingston Antiphospholipid Antibody (KAPS) Study Group.. Am J Clin Pathol 1990; 94: 476-84.
21 Pradelles P, Grassi J, Maclouf J. Enzyme immunoassays of eicosanoids using acetylcholine esterase as label: An alternative to radioimmunoassay.. Anal Chem 1985; 57: 1170-3.
22 Lellouche F, Fradin A, FitzGerald G, Maclouf J. Enzyme immunoassay measurement of the urinary metabolites of thromboxane A₂ and prostacyclin.. Prostaglandins 1990; 40: 297-310.
23 Patrono C, Ciabattoni G, Remuzzi G, Gotti E, Bombardieri S, Di Minno O, Tartarelli GA, Simonetti BM, Pierucci A. Functional significance of renal prostacyclin and thromboxane A₂ production in patients with systemic lupus erythematosus.. J Clin Invest 1985; 76: 1011-8.
24 Forastiero RR, Martinuzzo ME, Kordich LC, Carreras LO. Reactivity to β₂-glycoprotein I clearly differentiates anticardiolipin antibodies from anti-phospholipid syndrome and syphilis.. Thromb Haemost 1996; 75: 717-20.
25 Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Comparison of the effects of anticardiolipin antibodies from patients with the antiphospholipid syndrome and with syphilis on platelet activation and aggregation.. Thromb Haemost 1995; 73: 529-34.
26 Lin YL, Wang CT. Activation of human platelets by the rabbit anticardiolipin antibodies.. Blood 1992; 80: 3135-43.
27 Balestrieri G, Tincani A, Spatola L, Allegri F, Prati E, Cattaneo R, Valesini G, Del Papa N, Meroni P. Anti-beta₂-glycoprotein I antibodies: a marker of antiphospholipid syndrome?. Lupus 1995; 4: 122-30.
28 Roubey RAS, Maldonado MA, Byrd SN. Comparison of an enzyme-linked immunosorbent assay for antibodies to β₂-glycoprotein I and a conventional anticardiolipin immunoassay.. Arthritis Rheum 1996; 39: 1606-9.
29 Shi W, Chong BH, Chesterman CN. Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants.. Blood 1993; 81: 1255-62.
30 Arvieux J, Roussel B, Pouzol P, Colomb MG. Platelet activating properties of murine monoclonal antibodies to beta 2-glycoprotein I.. Thromb Haemost 1993; 70: 336-41.
31 Arnout J. The pathogenesis of the antiphospholipid syndrome: A hypothesis based on parallelisms with heparin-induced thrombocytopenia.. Thromb Haemost 1996; 75: 536-41.