The antiphospholipid antibodies (aPL) present in autoimmune disorders are associated with thromboembolic episodes, and their binding to phospholipids (PL) is mediated by a plasma cofactor, β2-glycoprotein I (β2GPI). Both PL and β2GPI seem necessary for binding, thus indicating that the two components comprise the epitope against which aPL are directed. Using an anti-β2GPI antibody ELISA with the antigen adsorbed onto polyvinylchloride (PVC) plates, we detected high antibody titres in 12 out of 12 plasmas from patients with the antiphospholipid syndrome. No or very low positivity was obtained when the same ELISA was carried out in polystyrene (PST) plates, while an increasing positivity was found when processed (i.e. more hydrophilic) or COOH-surface PST plates were used. When (β2GPI dependent IgG-aPL were purified using agarose-immobilized cardio- lipin, 4 out of 4 preparations were highly positive in anti-β2GPI antibody ELISA using PVC plates, while β2GPI was not fully recognized by aPL-IgG when adsorbed onto PST plates. These findings demonstrate that aPL are, in fact, anti-β2GPI antibodies directed against a cryptic epitope which is expressed when β2GPI is bound to anionic phospholipid, or another suitable surface.
References
1
Harris EN,
Gharavi AE,
Hughes GR V.
Anti-phospholipid antibodies. Clin Rheum Dis 1985; 11: 591-609
2
Gharavi AE,
Harris EN,
Asherson RA,
Hughes GR V.
Anticardiolipin anti bodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 1-6
5
Harris EN,
Gharavi AE,
Boey ML,
Patel BM,
Mackworth-Young CB,
Loi-zou S,
Hughes GR V.
Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2: 1211-1214
7
Johansson AE,
Lassus A.
The occurrence of circulating anticoagulants in patients with syphilitic and biologically false positive antilipoidal antibodies. Ann Clin Res 1974; 6: 105-108
9
Costello PB,
Green FA.
Reactivtiy pattern of human anticardiolipin and other antiphospholipid antibodies in syphilitic sera. Infect Immunol 1986; 51: 771-775
13
Roubey RA S,
Pratt CW,
Buyon JP,
Winfield JB.
Lupus anticoagulant activity of autoimmune antiphopholipid antibodies is dependent upon β2-glycoprotein I. J Clin Invest 1992; 90: 1100-1104
14
Ordi J,
Selva A,
Monegal F,
Procel JM,
Martinez-Costa X,
Vilardell M.
Anticardiolipin antibodies and dependence of a serum cofactor. A mechanism of thrombosis J Rheumatol 1993; 20: 1321-1324
15
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
16
Galli M,
Comfurius P,
Maassen C,
Hemker HC,
De Baets MH,
Van Brieda-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; 335: 1544-1547
17
Matsuura E,
Igarashi Y,
Fujimoto M,
Ichikava K,
Koike T.
Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990; 336: 177-178
19
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
22
Biasiolo A,
Pengo V.
Antiphospholipid antibodies are not present in the membrane of gel-filtered platelets of patients with IgG anticardiolipin antibodies, lupus anticoagulant and thrombosis. Blood Coag Fibrinol 1993; 4: 425-428
23
Harris EN,
Gharavi AE,
Patel SP,
Hughes GV R.
Evaluation of the anticardiolipin antibody test: report of an international workshop held 4 April 1986. Clin Exp Immunol 1987; 68: 215-222
25
Triplett DA,
Brandt JT,
Kaczor D,
Shaeffer J.
Laboratory diagnosis of lupus inhibitors: A comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization procedure. Am J Clin Pathol 1983; 79: 678-682
28
Pengo V,
Ruffatti A,
Baritussio A,
De Marco L,
Todesco S,
Girolami A.
Serum of normal subjects contains IgG with antibody-like specificity for phospholipids. Folia Haematol 1984; 111: 681-685
30
Pengo V,
Biasiolo A.
Purification of anticardiolipin and lupus anticoagulant activities by using cardiolipin immobilized on agarose beads. Thromb Res 1993; 72: 423-430
32
Inoue K,
Nojima S.
Immunochemical studies of phospholipids. IV. The reactivities of antisera against natural cardiolipin and synthetic cardiolipin analogues-containing antigens. Chem Phys Lipids 1969; 3: 70-77
34
Hohmann A,
Comacchio R,
Boswarva V,
Sutjita M,
Bradley J.
The H3 anti-phospholipid idiotype is found in patients with systemic lupus erythematosus (SLE) but not in patients with syphilis. Clin exp Immunol 1991; 86: 207-211
35
Oosting JD,
Derksen RH W M,
Entjes HT I,
Bouma BN,
De Groot PG.
Lupus anticoagulant activity is frequently dependent on the presence of β2-Glycoprotein I. Thromb Haemost 1992; 67: 499-502
36
Galli M,
Comfurius P,
Barbui T,
Zwaal RF A,
Bevers EM.
Anticoagulant activity of β2glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies. Thromb Haemost 1992; 68: 297-300
39
Gharavi AZ,
Sammaritano LR,
Wen J,
Elkon KB.
Induction of antiphospholipid antibodies by immunization with β2-glycoprotein I (Apolipoprotein H). J Clin Invest 1992; 90: 1105-1109
40
Nimpf J,
Bevers EM,
Bomans PH H,
Till U,
Wurm H,
Kostner GH,
Zwaal RF A.
Prothrombinase activity of human platelets is inhibited by β2-glyco-protein I. Biochim Biophys Acta 1986; 844: 142-149
43
Canfield WM,
Kisiel W.
Evidence of normal functional levels of activated protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest 1982; 70: 1260-1272
44
Arvieux J,
Roussel B,
Jacob MC,
Colomb MG.
Measurement of anti-phospholipid antibodies by ELISA using β2-glycoprotein I as an antigen. J Immunol Meth 1991; 143: 223-229
45
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: 457-462
46
Berger A,
German JB,
Gershwin ME.
Implication of modifying cardiolipin acyl composition by diet. 1. Cardiolipin acyl chain is an important determinant in the binding to antiphospholipid antibodies in SLE sera. J Autoimmun 1992; 5: 229-241
47
Hasselaar P,
Derksen RH W M,
Blokzijl L,
de Groot PG.
Crossreactivity of antibodies directed against cardiolipin, DNA, endothelial cells and blood platelets. Thromb Haemost 1990; 63: 169-173
48
Bevers EM,
Galli M,
Barbui T,
Comfurius P,
Zwaal RF A.
Lupus anticoagulant IgG’s (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost 1991; 66: 629-632
