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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
1   The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA
,
Silvia S Pierangeli
1   The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA
,
Samuel Wellhausen
2   James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, KY, USA
,
Nigel E Harris
1   The Antiphospholipid Standardization Laboratory, Division of Rheumatology, KY, USA
› Author Affiliations
Further Information

Publication History

Received 01 August 1994

Accepted after resubmission 28 October 1994

Publication Date:
09 July 2018 (online)

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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.

 

  • References

  • 1 Harris EN, Gharavi AE, Hughes GR V. Anti-phospholipid antibodies. Clin Rheum Dis 1985; 11: 591-609
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 6 Sammaritano LR, Lockshin MD, Gharavi AE. Antiphospholipid antibodies differ in aPL cofactor requirement. Lupus 1992; 1: 51-56
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 11 Lin Y-L, Wang C-T. Activation of human platelets by the rabbit anticardiolipin antibodies. Blood 1992; 80: 3134-3143
    PubMedGoogle Scholar
  • 12 Harris EN. Syndrome of the Black Swan. Br J Rheumatol 1987; 26: 324
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 14 Gharavi AE, Harris EN, Asherson RA, Hughes GR V. Anticardiolipin antibody: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 1-6
    CrossrefPubMedGoogle Scholar
  • 15 Harris EN. Annotation. Antiphospholipid Antibodies. Br J Haematol 1990; 74: 1-9
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 17 Triplett DA, Brandt J. Laboratory identification of lupus anticoagulant. Br J Haematol 1989; 73: 139-142
    CrossrefPubMedGoogle Scholar
  • 18 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioral patterns. Br J Haematol 1978; 40: 143-150
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 22 Rauch J, Meng G, Tannenbaum H. Lupus anticoagulant and antiplatelet properties of human hybridoma autoantibodies. J Immunol 1987; 139: 2598-2604
    PubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 38 Pengo V, Heine MJ, Thiagarajan P, Shapiro SS. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood 1987; 70: 69-76
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 40 Violi F, Valesini G, Ferro D, Tincani A, Balestrieri G, Balsano F. Anticoagulant activity of anticardiolipin antibodies. Thromb Res 1986; 44: 543-547
    CrossrefPubMedGoogle Scholar