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Thromb Haemost 1996; 75(05): 717-720
DOI: 10.1055/s-0038-1650354
Original Article
Schattauer GmbH Stuttgart

Reactivity to β2 Glycoprotein I Clearly Differentiates Anticardiolipin Antibodies from Antiphospholipid Syndrome and Syphilis

R R Forastiero
1   The University Institute of Biomedical Sciences and Institute of Cardiology and Cardiovascular Surgery, Favaloro Foundation, University of Buenos Aires, Buenos Aires, Argentina
,
M E Martinuzzo
1   The University Institute of Biomedical Sciences and Institute of Cardiology and Cardiovascular Surgery, Favaloro Foundation, University of Buenos Aires, Buenos Aires, Argentina
,
L C Kordich
2   The Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina
,
L O Carreras
1   The University Institute of Biomedical Sciences and Institute of Cardiology and Cardiovascular Surgery, Favaloro Foundation, University of Buenos Aires, Buenos Aires, Argentina
› Author Affiliations
Further Information

Publication History

Received 12 September 1995

Accepted after resubmission 24 January 1996

Publication Date:
10 July 2018 (online)

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Summary

Anticardiolipin antibodies (aCL) detected by standard ELISA are found in association with autoimmune and infectious diseases. It is now recognized that P2 glycoprotein I (β2GPI) is a cofactor for aCL binding to cardiolipin (CL). To examine differences in cofactor requirements, aCL positive sera from patients with the antiphospholipid syndrome (APS) and syphilis were studied. Using an ELISA with human purified P2GPI adsorbed onto irradiated plates, we detected high binding activity in 29 out of 35 samples from APS patients and low in only 1 out of 37 aCL positive syphilis sera. Moreover, a good correlation (r = 0.79) was also observed in the former group between aCL and anti β2GPI. Whole IgG and affinity purified IgG aCL from APS patients did not bind to CL in the absence of β2GPI, but recognized β2GPI on irradiated plates in the absence of phospholipids. In contrast, IgG purified from syphilis patients only bound to CL alone. Taken together, these data indicate that performing both ELISA (aCL and anti β2GPI) it could be possible to distinguish aCL from autoimmune or infectious diseases.

 

  • References

  • 1 Harris EN. Annotation. Antiphospholipid antibodies. Br J Haematol 1990; 74: 1-9
    PubMedGoogle Scholar
  • 2 Exner T, Triplett DA. Lupus anticoagulants: characteristics, methods of laboratory detection and some clinical associations. In: Phospholipid-Binding Antibodies Harris EN, Exner T, Hughes GRV, Asherson RA. eds. Boca Raton, Florida (USA): CRC Press; 1991: 141-158
  • 3 Harris EN. The Second International Anticardiolipin Standardization Workshop/The Kingston Antiphospholipid Antibody (KAPS) Study Group. Am J Clin Pathol 1990; 94: 476-484
    CrossrefPubMedGoogle Scholar
  • 4 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: 373-386
  • 5 Meyer O, Cyna L, Bourgeois P, Kahn MF, Ryckewaert A. Profile and cross-reactivities of antiphospholipid antibodies in systemic lupus erythematosus and syphilis. Clin Rheumatol 1987; 6: 369-377
    CrossrefPubMedGoogle Scholar
  • 6 Koike T, Sueishi M, Funaki H, Tomioka H, Yoshida S. Anti-phospholipid antibodies and biological false positive serological test for syphilis in patients with systemic lupus erythematosus. Clin Exp Immunol 1984; 56: 193-199
    PubMedGoogle Scholar
  • 7 Harris EN, Gharavi AE, Wasley GD, Hughes GRV. Use of an enzymelinked immunosorbent assay and of inhibition studies to distinguish between antibodies to cardiolipin from patients with syphilis or autoimmune disorders. J Infect Dis 1987; 157: 23-31
    PubMedGoogle Scholar
  • 8 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
  • 9 Ordi J, Selva A, Monegal F, Porcel JM, Martinez-Costa X, Vilardell M. Anticardiolipin antibodies and dependence of a serum cofactor. A mechanism of thrombosis. J Rheumatol 1993; 20: 1321-1324
    PubMedGoogle Scholar
  • 10 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990; 336: 177-178
    PubMedGoogle Scholar
  • 11 Galli M, Comfurius P, Maassen C, Hemker HC, De Baets MH, van Breda-Vriesman PJC, Barbui T, Zwaal RFA, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-1547
    CrossrefPubMedGoogle Scholar
  • 12 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: 4120-4124
    CrossrefPubMedGoogle Scholar
  • 13 Arvieux J, Roussel B, Jacob MC, Colomb MG. Measurement of antiphospholipid antibodies by ELISA using β2 glycoprotein I as an antigen. J Immunol Methods 1991; 143: 223-229
    CrossrefPubMedGoogle Scholar
  • 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: 181-186
    CrossrefPubMedGoogle Scholar
  • 15 Matsuura E, Igarashi Y, Yasuda T, Koike T, Triplett DA. Anticardiolipin antibodies recognize β2 glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-462
    CrossrefPubMedGoogle Scholar
  • 16 Pengo V, Biasiolo A, Fior MG. Autoimmune antiphospholipid antibodies are directed against a cryptic epitope expressed when β2-glycoprotein I is bound to a suitable surface. Thromb Haemost 1995; 73: 29-34
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Martinuzzo ME, Forastiero RR, Carreras LO. Anti β2 glycoprotein I: detection and association with thrombosis. Br J Haematol 1995; 89: 397-402
    CrossrefPubMedGoogle Scholar
  • 18 Roubey RAS, Eisenberg RA, Harper MF, Winfield JB. “Anticardiolipin” autoantibodies recognize β2 glycoprotein I in the absence of phospholipid. Importance of antigen density and bivalent binding. J Immunol 1995; 154: 954-960
    PubMedGoogle Scholar
  • 19 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
  • 20 Bradford MM. A rapid and sensitive method for the quantification of microgram quantita-tives of protein utilizing the principle of protein dyebinding. Anal Biochemistry 1976; 72: 248-254
    CrossrefPubMedGoogle Scholar
  • 21 Chamley LW, McKay EJ, Pattison NS. Cofactor dependent and cofactor independent anticardiolipin antibodies. Thromb Res 1991; 61: 291-299
    CrossrefPubMedGoogle Scholar
  • 22 Sammaritano LR, Lockshin MD, Gharavi AE. Antiphospholipid antibodies differ in aPL cofactor requirement. Lupus 1992; 1: 83-90
    PubMedGoogle Scholar
  • 23 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Suzuki T, Sumida T, Yasuda T, Koike T. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J immunol 1992; 148: 3885-3891
    PubMedGoogle Scholar
  • 24 Harris EN, Pierangeli S, Barquinero J, Ordi-Ros J. Anticardiolipin antibodies and binding of anionic phospholipids and serum protein. Lancet 1991; 336: 505-506
    PubMedGoogle Scholar
  • 25 Pierangeli SS, Harris EN, Davis SA, De Lorenzo G. β2-glycoprotein 1 (β2GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies. Br J Haematol 1992; 82: 565-570
    CrossrefPubMedGoogle Scholar
  • 26 Amiral J, Larrivaz I, Cluzeau D, Adam M. Standardization of immunoassays for antiphospholipid antibodies with β2GPI and role of other phospholipid cofactors. Haemostasis 1994; 24: 191-203
    PubMedGoogle Scholar
  • 27 Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA. A phospholipid-β-Glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. Lupus 1992; 1: 75-81
    CrossrefPubMedGoogle Scholar
  • 28 Matsuda J, Saitoh N, Gohchi K, Gotoh M, Tsukamoto M. Distinguishing β2-glycoprotein I dependent (systemic lupus erythematosus type) and independent (syphilis type) anticardiolipin antibody with Tween 20. Br J Haematol 1993; 85: 799-802
    CrossrefPubMedGoogle Scholar
  • 29 Aoki K, Matsuura E, Sasa H, Yagami Y, Dudkiewicz AB, Gleicher N. β2-Glycoprotein I-dependent and -independent anticardiolipin antibodies in healthy pregnant women. Human Reprod 1994; 9: 1849-1851
    CrossrefPubMedGoogle Scholar
  • 30 Harris EN, Gharavi AE, Patel SP, Hughes GRV. Evaluation of the anticardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol 1987; 68: 215-222
    PubMedGoogle Scholar
  • 31 Cabral AR, Cabiedes J, Alarcon-Segovia D. Tween-20 detaches cardiolipin from ELISA plates and renders aCL undetectable regardless of the presence of 2-glycoprotein-I (β2GP-I). Lupus 1994; 3: 329
    PubMedGoogle Scholar
  • 32 Keeling DM, Wilson AJG, Mackie IJ, Machin SJ, Isenberg DA. Some antiphospholipid antibodies bind to β2-glycoprotein-I in the absence of phospholipid. Br J Haematol 1992; 82: 571-574
    CrossrefPubMedGoogle Scholar
  • 33 Arvieux J, Roussel B, Ponard D, Colomb MG. IgG2 subclass restriction of anti-β2 glycoprotein 1 antibodies in autoimmune patients. Clin Exp Immunol 1994; 95: 310-315
    PubMedGoogle Scholar
  • 34 Hunt J, Krilis S. The fifth domain of β2-glycoprotein-I contains a phospholipid binding site (cys 281-cys 288) and a region recognized by anticardiolipin antibodies. J Immunol 1994; 152: 653-659
    PubMedGoogle Scholar
  • 35 Wagenknecht DR, McIntyre JA. Changes in β2-glycoprotein-I antigenicity induced by phospholipid binding. Thromb Haemost 1993; 69: 361-365
    Article in Thieme ConnectPubMedGoogle Scholar