Thromb Haemost 1998; 80(02): 250-257
DOI: 10.1055/s-0037-1615183
Rapid Communication
Schattauer GmbH

Heterogeneity of Lupus Anticoagulant (LA) Antibodies: LA Activity in Dilute Russell’s Viper Venom Time and Dilute Kaolin Clotting Time Detect Different Populations of Antibodies in Patients with the “Antiphospholipid” Syndrome

David A. Kandiah
1   From the Department of Immunology, Allergy and Infectious Disease and Department of Medicine, University of New South Wales, The St. George Hospital, Kogarah, New South Wales, Australia
,
Steven A. Krilis
1   From the Department of Immunology, Allergy and Infectious Disease and Department of Medicine, University of New South Wales, The St. George Hospital, Kogarah, New South Wales, Australia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 08. Juli 1997

Accepted after resubmission 02. April 1998

Publikationsdatum:
08. Dezember 2017 (online)

Summary

“Antiphospholipid” (aPL) antibodies comprise two main groups of antibodies, lupus anticoagulant (LA) antibodies and “anticardiolipin” (aCL) antibodies which can be separated by certain chromatographic techniques. In this study we analysed the plasma of 10 patients with aPL antibodies, and were able to demonstrate that in four patients with both clotting test reactivities, the dilute Russell’s Viper Venom Time (dRVVT) activity can be separated from the dilute Kaolin Clotting Time (dKCT) reactivity by using a polyacrylamide-immobilised phosphatidylserine column but not with phospholipid liposomes. The differential reactivity of the autoantibodies in this patient population is not due to binding to β2GPI, prothrombin or protein C in solid-phase immunoassays. Hence LA antibodies detected in different phospholipid-dependent clotting tests detect different populations of antibodies in some APS patients and the routine detection of LA antibodies should be performed with at least two clotting tests looking at different coagulation reactions.

 
  • References

  • 1 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193-280.
  • 2 Kandiah DA, Krilis SA. Immunology and methods of detection of antiphospholipid antibodies. In: The Antiphospholipid Syndrome. Asherson RA, Cervera R, Piette J-C, Shoenfeld Y. eds. CRC Press; Boca Raton, FL: 1996. pp 29-48.
  • 3 Kandiah DA, Krilis SA. Laboratory detection of antiphospholipid antibodies. Lupus 1996; 5: 160-2.
  • 4 McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Antiphospholipid 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: 4120-4.
  • 5 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.
  • 6 Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize β2-glycoprotein I structure altered by interacting with an oxygen modified solid-phase surface. J Exp Med 1994; 179: 457-62.
  • 7 Roubey RAS, Eisenberg RA, Harper MF, Winfield JB. “Anticardiolipin” autoantibodies recognize β2-glycoprotein I in the absence of phospholipid. J Immunol 1995; 154: 954-60.
  • 8 Oosting JD, Derksen RHWM, Entjes HT, Bouma BN, de Groot P. Lupus anticoagulant activity is frequently dependent on the presence of β2-glyco-protein I. Thromb Haemost 1992; 67: 499-502.
  • 9 Keeling DM, Wilson AJG, Mackie IJ, Isenberg DA, Machin SJ. Lupus anticoagulant activity of some antiphospholipid antibodies against phospholipid bound β2-glycoprotein I. J Clin Pathol 1993; 46: 665-7.
  • 10 Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RFA. Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-32.
  • 11 Cariou R, Tobelem G, Bellucci S, Soria J, Maclouf J, Caen J. Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells – inhibition of thrombomodulin-dependent protein C activation. Thromb Haemost 1988; 60: 54-8.
  • 12 Oosting JD, Derksen RHWM, Bobbink IWG, Hackeng TM, Bouma BN, de Groot 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: 2618-25.
  • 13 Smirnov MD, Triplett DT, Comp PC, Esmon NL, Esmon CT. On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies. J Clin Invest 1995; 95: 309-16.
  • 14 Sugi T, McIntyre JA. Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen-PE complex. Blood 1995; 86: 3083-9.
  • 15 Horbach DA, van Oort E, Donders RCJM, Derksen RHWM, de Groot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Thromb Haemost 1996; 76: 916-24.
  • 16 Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell’s Viper Venom Time for the diagnosis of lupus anticoagulant. Blood 1986; 68: 869-74.
  • 17 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioral patterns. Br J Haematol 1978; 40: 143-51.
  • 18 Galli M, Finazzi G, Bevers EM, Barbui T. Kaolin Clotting Time and dilute Russell’s Viper Venom Time distinguish between prothrombin-dependent and β2-glycoprotein I-dependent antiphospholipid antibodies. Blood 1995; 86: 617-23.
  • 19 Callahan JB, Manares CC, Moll S, Ortel TL. Inability to distinguish between thrombotic and non-thrombotic antiphospholipid antibody positive patients with Kaolin Clotting Time and dilute Russell’s Viper Venom Assay ratios. Lupus 1996; 5: 530 (Abstract 111).
  • 20 Triplett DA. Antiphospholipid-protein antibodies: Laboratory detection and clinical relevance. Thromb Research 1995; 78: 1-31.
  • 21 Sletnes KE, Gravem K, Wisloff F. Preparation of plasma for the detection of lupus anticoagulants and antiphospholipid antibodies. Thromb Research 1992; 66: 43-53.
  • 22 Pengo V, Thiagarajan P, Shapiro SS, Heine MJ. Immunological specificity and mechanism of action of IgG lupus anticoagulants. Blood 1987; 70: 69-76.
  • 23 McNeil HP, Krilis SA, Chesterman CN. Purification of antiphospholipid antibodies using a new affinity method. Thromb Research 1988; 52: 641-8.
  • 24 Monestier M, Kandiah DA, Kouts S, Novick KE, Ong GL, Radic MZ, Krilis SA. Monoclonal antibodies from NZW x BXSB/F1 mice to β2-glycoprotein I and cardiolipin. Species specificity and charge-dependent binding. J Immunol 1996; 156: 2631-41.
  • 25 Ichikawa K, Khamashta M, Koike T, Matsuura E, Hughes GRV. β2-glyco-protein I reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome. Arthritis and Rheumatism 1994; 37: 1453-61.
  • 26 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: An update. Thromb Haemost 1995; 74: 1185-90.
  • 27 Kandiah DA, Krilis SA. Immunology of antiphospholipid antibodies and their interaction with plasma proteins. Lupus 1996; 5: 153-5.
  • 28 Pengo V, Biasiolo A, Brocco T, Tonetto S, Rufatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies. Thromb Haemost 1996; 75: 721-4.
  • 29 Roubey RAS, Pratt CW, Buyon JP, Winfield JB. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon β2-glycoprotein I. J Clin Invest 1992; 90: 1100-4.
  • 30 Permpikul P, Rao LVM, Rapaport SI. Functional and binding studies of the roles of prothrombin and β2-glycoprotein I in the expression of lupus anticoagulant activity. Blood 1994; 83: 2878-92.
  • 31 Govers-Riemslag JW, Janssen MP, Zwaal RFA, Rosing J. Prothrombin activation on dioleoylphosphatidylcholine membranes. European J Biochemistry 1994; 220: 131-8.