Comparison of the Effects of Anticardiolipin Antibodies from Patients with the Antiphospholipid Syndrome and with Syphilis on Platelet Activation and Aggregation

Andrew L Campbell; Silvia S Pierangeli; Samuel Wellhausen; Nigel E Harris

doi:10.1055/s-0038-1653808

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1995; 73(03): 529-534
DOI: 10.1055/s-0038-1653808

Original Articles

Platelets

Schattauer GmbH Stuttgart

Comparison of the Effects of Anticardiolipin Antibodies from Patients with the Antiphospholipid Syndrome and with Syphilis on Platelet Activation and Aggregation

Andrew L Campbell

¹The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA

,

Silvia S Pierangeli

¹The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA

,

Samuel Wellhausen

²James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, KY, USA

,

Nigel E Harris

¹The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA

› Institutsangaben

Abstract

als PDF herunterladen

Summary

Anticardiolipin antibodies (aCL) are induced both in the Antiphospholipid Syndrome (APS) and syphilis, but thrombosis, thrombocytopenia, and pregnancy loss occur only in the APS. Differences in specificity and function of aCL antibodies might explain clinical differences between APS and syphilis. This study compared the effects on platelet activation and aggregation of affinity purified IgG anticardiolipin antibodies from 6 patients with the APS (IgG-APS) and 5 patients with syphilis (IgG-syph). Platelet aggregation was studied by aggregometry and platelet activation by flow cytometry. In the presence of low concentrations of thrombin, ADP, or collagen, all 6 IgG-APS samples induced platelet aggregation and activation, but none of the IgG-syph samples had this effect. In the absence of platelet agonists, only 3 of 6 IgG-APS caused platelet aggregation and none caused platelet activation; IgG-syph had no effect. The IgG-APS samples but not IgG-syph bound phosphatidylserine by ELISA. We conclude that polyclonal antibodies specific for phosphatidylserine may induce platelet activation and aggregation in the presence of low concentrations of platelet agonists.

PDF (569 kb)

Referenzen

References
1 Harris EN, Gharavi AE, Hughes GR V. Anti-phospholipid antibodies. Clin Rheum Dis 1985; 11: 591-609
2 Harris EN, Gharavi AE, Wasley GD, Hughes GR V. Use of an enzyme-linked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders. J Infect Dis 1988; 157: 23-31
3 Mouritsen S, Hoier-Madsen M, Wiik A, Orum O, Standberg-Pedersen N. The specificity of anti-cardiolipin antibodies from syphilis patients and from patients with systemic lupus erythematosus. Clin Exp Immunol 1989; 76: 178-183
4 Levy RA, Gharavi AE, Sammaritano LR, Habina L, Qamar T, Lockshin MD. Characteristics of IgG antiphospholipid antibodies in patients with systemic lupus erythematosus and syphilis. J Rheumatol 1990; 17: 1036-1041
5 Matsuura E, Igarashi V, Fujimoto M, Ichikawa K, Suzuki T, Sumida T, Ya-suda T, Koike T. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148: 3885-3891
6 Sammaritano LR, Lockshin MD, Gharavi AE. Antiphospholipid antibodies differ in aPL cofactor requirement. Lupus 1992; 1: 51-56
7 Pierangeli SS, Krnic S, Goldsmith G, Campbell A, Harris EN. Functional differences in anticardiolipin antibodies from patients with syphilis and the antiphospholipid syndrome. Infect Immun 1994; 62: 4081-4084
8 Lellouche F, Martinuzzo M, Said P, Maclouf J, Carreras LO. Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant. Blood 1991; 78: 2894-2899
9 Martinuzzo ME, Maclouf J, Carreras LO, Levy-Toledano S. Antiphospholipid antibodies enhance thrombin induced platelet activation and thromboxane formation. Thromb Haemost 1993; 70: 667-671
10 Escolar G, Font J, Reverter JC, Lopez-Soto A, Garrido M, Cervera R, Ingelmo M, Castillo R, Ordinas A. Plasma from systemic lupus erythematosus patients with antiphospholipid antibodies promotes platelet aggregation. Studies in a perfusion system Arterioscleroses Thromb 1992; 12: 196-200
11 Lin Y-L, Wang C-T. Activation of human platelets by the rabbit anticardiolipin antibodies. Blood 1992; 80: 3134-3143
12 Harris EN. Syndrome of the Black Swan. Br J Rheumatol 1987; 26: 324
13 Pierangeli SS, Harris EN, Davis SA, DeLorenzo G. β₂glycoprotein 1 enhances cardiolipin binding activity but is not the target antigen for antiphospholipid antibodies. Br J Haematol 1992; 82: 565-567
14 Gharavi AE, Harris EN, Asherson RA, Hughes GR V. Anticardiolipin antibody: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 1-6
15 Harris EN. Annotation. Antiphospholipid Antibodies. Br J Haematol 1990; 74: 1-9
16 Harris EN, Pierangeli S, Birch D. Anticardiolipin wet workshop report: Vth International Symposium on antiphospholipid antibodies. Am J Clin Pathol 1994; 101 (05) 616-624
17 Triplett DA, Brandt J. Laboratory identification of lupus anticoagulant. Br J Haematol 1989; 73: 139-142
18 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioral patterns. Br J Haematol 1978; 40: 143-150
19 Larsen E, Celi A, Gilbert GE, Furie BC, Erban JK, Bonsanti R, Wagner DD, Furie B. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989; 59: 305-312
20 Harris EN, Asherson RA, Gharavi AE, Morgan SH, Derue G, Hughes GR V. Thrombocytopenia in SLE and related autoimmune disorders: association with anti-cardiolipin antibody. Br J Haematol 1985; 59: 227-230
21 Khamashta MA, Harris EN, Gharavi AE, Derue G, Hughes GR V. Immune mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes. Ann Rheum Dis 1988; 47: 849-854
22 Rauch J, Meng G, Tannenbaum H. Lupus anticoagulant and antiplatelet properties of human hybridoma autoantibodies. J Immunol 1987; 139: 2598-2604
23 Hasselaar P, Derksen RH W M, Blokzijl L, deGroot PG. Crossreactivity of antibodies directed against cardiolipin, DNA, endothelial cells and blood platelets. Thromb Haemost 1990; 63: 169-173
24 Out HJ, deGroot PG, van Vliet M, de Gast PG, Nieuwenhuis HK, Derksen RH W M. Antibodies to platelets in patients with anti phospholipid antibodies. Blood 1991; 77: 2655-2659
25 Shi W, Chong BH, Chesterman CN. β₂-glycoprotein is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. Blood 1993; 81: 1255-1262
26 Slupsky JR, Cawley JC, Grifith LS, Shaw AR E, Zugel M. Role of FcγRII in platelet activation by monoclonal antibodies. J Immunol 1992; 148: 3189-3194
27 Rote NS, Ng A-K, Dostal-Johnson DA, Nididson SL, Siekman R. Immunologic detection of phosphatidylserine externalization during thrombin-induced platelet activation. Clin Immunol Immunopathol 1993; 66: 193-200
28 Arvieux J, Roussel B, Pouzol P, Colomb MG. Platelet activating properties of murine monoclonal antibodies to β₂Glycoprotein 1. Thromb Haemost 1993; 70: 336-341
29 Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RF A. Lupus anticoagulant (LA) IgG’s are not directed to phospholipids only but to a complex lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-632
30 Bevers EM, Comfurius P, VanRijn JL M L, Hemker HC, Zwaal RF A. Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 1982; 122: 429-436
31 Galli M, Comfurius P, Maasen C, Heinker HC, deBaets MH, Van-Breda Vriesman PJ C, Barbui T, Zwaal RF A, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 336: 544-547
32 McNeil HP, Simpson RJ, Chesterman CN, Krilis S. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β₂glycoprotein 1 (apolipoprotein H). Proc Natl Acad Sci 1990; 87: 4120-4124
33 Galli M, Comfurius P, Barbui T, Zwaal RF A, Bevers EM. Anticoagulant activity of β₂lycoprotein 1 is potentiated by a distinct subgroup of anticar- diolipin antibodies. Thromb Haemost 1992; 68: 297-300
34 Oosting JD, Derksen RH W M, Bobbink IW G, Hackeng TM, Bouma BN, deGroot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C or protein S: an explanation for their pathogenic mechanism. Blood 1993; 81: 2618-2625
35 Harris EN, Gharavi AE, Tincani A, Chan JK H, Englert H. Affinity purified anti-cardiolipin and anti-DNA antibodies. J Clin Lab Immunol 1985; 17: 155-162
36 Pierangeli SS, Harris EN, Goldsmith G, Gharavi AE, Branch DW, Dean WL. Are immunoglobulins with lupus anticoagulant activity specific for phospholipids. Br J Haematol 1993; 85: 124-132
37 Goldsmith GH, Pierangeli SS, Branch DW, Gharavi AE, Harris EN. Inhibition of prothrombin activation by antiphospholipid antibodies β₂glycopro-tein 1. Br J Haematol 1994; 87: 548-554
38 Pengo V, Heine MJ, Thiagarajan P, Shapiro SS. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood 1987; 70: 69-76
39 Pengo V, Biasiolo A. Purification of anticardiolipin and lupus anticoagulant activities by using cardiolipin immobilized on agarose beads. Thromb Res 1993; 72: 423-430
40 Violi F, Valesini G, Ferro D, Tincani A, Balestrieri G, Balsano F. Anticoagulant activity of anticardiolipin antibodies. Thromb Res 1986; 44: 543-547