Heterogeneous Recognition of beta 2-glycoprotein I by Antibodies from Antiphospholipid Syndrome Patients

J. Guerin; R. Sim; B-B. Yu; J. Ferluga; C. Feighery; J. Jackson

doi:10.1055/s-0037-1614031

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2000; 84(03): 374-380
DOI: 10.1055/s-0037-1614031

Commentary

Schattauer GmbH

Heterogeneous Recognition of beta 2-glycoprotein I by Antibodies from Antiphospholipid Syndrome Patients

J. Guerin

¹From the Department of Immunology, St. James’s Hospital, Dublin

,

R. Sim

²MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK

,

B-B. Yu

²MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK

,

J. Ferluga

²MRC Immunochemistry Unit, Dept. of Biochemistry, University of Oxford, UK

,

C. Feighery

¹From the Department of Immunology, St. James’s Hospital, Dublin

,

J. Jackson

³Dublin Institute of Technology, Dublin, Ireland

› Institutsangaben

Abstract

Summary

Beta 2-glycoprotein I plays a pivotal role in the binding of antiphospholipid antibodies to phospholipid in patients with antiphospholipid syndrome. In this study the nature of the epitopes on beta 2-glycoprotein I (β2-GPI) recognised by sera from antiphospholipid syndrome (APS) patients (n = 15) was investigated and compared to rabbit polyclonal and mouse monoclonal anti-β2-GPI antibodies. β2-GPI was only recognised when bound to a high affinity binding support. The antigenic epitope on β2-GPI recognised by all APS patients was also dependent on disulphide bond integrity. Digestion of β2-GPI with elastase rapidly destroyed the epitope(s) on β2-GPI recognised by antibodies in 91% of APS patients. The main cleavage occurred at tryptophan³¹⁶-lysine³¹⁷ in the fifth domain. Digestion with staphylococcal V8 protease resulted in a 50% reduction in antibody binding in 81% of patients and the cleavage sites mainly involved the first domain of the molecule. There was considerable variability in the recognition of six different species of β2-GPI by serum from APS patients. The epitopes on β2-GPI bound by APS sera appear conformationally determined in all patients but are quite heterogeneous in the regions of β2-GPI that are recognised.

Key words

Beta 2-glycoprotein I - antibodies - antiphospholipid syndrome - heterogeneity - species

Volltext

Referenzen

References
1 Hughes G, Harris N, Gharavi A. The anticardiolipin syndrome. J Rheumatol 1986; 13: 486-9.
2 Asherson R. A “primary” antiphospholipid syndrome?. J Rheumatol 1988; 15: 1742-6.
3 Hughes G. The antiphospholipid syndrome: ten years on. Lancet 1993; 342: 341-3.
4 Love P, Santoro S. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Ann Intern Med 1990; 112: 682-98.
5 Loizou SA, Walport MJ, Davies KA. The antiphospholipid syndrome in infectious diseases. In: The Antiphospholipid syndrome. Asherson RA, Cervesa R, Piette JC, Shoenfeld Y. eds. New York: CRC Press Inc; 1996: 267-84.
6 Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van BredaVriesman P, Barbui T, Zwaal R, Bevers E. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544-7.
7 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin co-factor(s) and differential diagnosis of autoimmune disease. Lancet 1990; 336: 177-8.
8 Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Suzuki T, Sumida T, Yasuda T. Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. J Immunol 1992; 148: 3885-91.
9 Schousboe I. Beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway. Blood 1985; 66: 1086-91.
10 Nimpf J, Bevers E, Bomans P, Till U, Wurm H, Kostner G, Zwaal R. Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I. Biochim Biophys Acta 1986; 884: 142-9.
11 Brighton T, Hoggs P, Dai Y-P, Murray H, Chong B, Chesterman C. Beta 2-glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant. Br J Haematol 1996; 93: 185-94.
12 Reid K, Day A. Structure-function relationships of the complement components Immunol. Today 1989; 10: 177-83.
13 Steinkasserer A, Estaller C, Weiss EH, Sim RB, Day A. Complete nucleotide and deduced amino acid sequence of human ß2-glycoprotein 1. Biochem J 1991; 227: 387-91.
14 Matsuura E, Igarashi M, Igarashi Y, Nagae H, Ichikawa K, Yasuda T, Koike T. Molecular definition of human β2-glycoprotein 1 (β2-GP1) by cDNA cloning and inter-species differences of β2-GP1 in alternation of anticardiolipin binding. Int Immunol 1991; 03: 1217-21.
15 Steinkasserer A, Barlow PN, Willis AC, Kertesz Z, Campbell ID, Sim RB, Norman DG. Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. FEBS Letts 1992; 313: 193-7.
16 Hunt J, Krilis S. The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies. J Immunol 1994; 152: 653-9.
17 Wang MX, Kandiah DA, Ichikawa K, Khamashta M, Hughes G, Koike T, Roubey R, Krilis SA. Epitope specificity of monoclonal anti-beta 2-glycoprotein I antibodies derived from patients with the antiphospholipid syndrome. J Immunol 1995; 155: 1629-36.
18 Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis S. Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity. J Immunol 1996; 157: 3744-51.
19 McNeil H, Simpson R, Chesterman C, Krilis S. Anti-phospholipid 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 1990; 87: 4120-4.
20 Pierangeli S, Harris E, Davis S, De Lorenzo G. β2-glycoprotein 1 (β2GP1) enhances cardiolipin binding activity but is not the antigen for antiphospholipid antibodies. Br J Haematol 1992; 82: 565-70.
21 Sheng Y, Kandiah DA, Krilis S. Anti-beta 2-glycoprotein I autoantibodies from patients with the “antiphospholipid” syndrome bind to beta 2-glycoprotein I with low affinity: dimerization of beta 2-glycoprotein I induces a significant increase in anti-beta 2-glycoprotein I antibody affinity. J Immunol 1998; 161 (04) 2038-43.
22 Forastiero RR, Martinuzzo ME, Carreras LO. Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. Clin Exp Immunol 1999; 118 (03) 480-6.
23 Jones JV, James H, Tan M, Mansour M. Antiphospholipid antibodies require beta 2-glycoprotein I (apolipoprotein H) as cofactor. J Rheumatol 1992; 19: 1397-1402.
24 Wagenknecht D, McIntyre J. Changes in ß2-glycoprotein 1 antigenicity induced by phospholipid binding. Thromb Haemost 1993; 69: 361-5.
25 Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179: 457-62.
26 Ichikawa K, Khamashta M, Koike T, Matsuura E, Hughes G. Beta 2-Glycoprotein I reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome. Arthritis Rheum 1994; 37: 1453-61.
27 Igarashi M, Matsuura E, Igarashi Y, Nagae H, Ichikawa K, Triplett D, Koike T. Human beta 2-glycoprotein I as an anticardiolipin cofactor determined using mutants expressed by a baculovirus system. Blood 1996; 87: 3262-70.
28 George J, Gilburd B, Hojnik M, Levy Y, Langevitz P, Matsuura E, Koike T, Shoenfeld Y. Target recognition of β2-glycoprotein I (β2-GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of ß2-GPI in antibody binding. J Immunol 1998; 160: 3917-23.
29 Iverson G, Victoria E, Marquis D. Anti-β2-glycoprotein I (β2-GPI) autoantibodies recognize an epitope on the first domain of β2-GPI. Proc Natl Acad Sci 1998; 95: 15542-6.
30 Alarcon-Segovia D, Sanchez-Guerrero J. Primary antiphospholipid syndrome. J Rheumatol 1989; 16: 482-8.
31 Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthritis Rheum 1999; 42: 1309-11.
32 Guerin J, Feighery C, Sim R, Jackson J. Antibodies to beta2-glycoprotein I – a specific marker for the antiphospholipid syndrome. Clin Exp Immunol 1997; 109: 304-9.
33 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
34 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 1979; 76: 4350-4.
35 Bevers E, Galli M, Barbui T. 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.
36 Permpikul P, Rao L, Rapaport S. Functional and binding studies of the roles of prothrombin and beta 2-glycoprotein I in the expression of lupus anticoagulant activity. Blood 1994; 83: 2878-92.
37 Roubey R, Maldonado M, Byrd S. Comparison of an enzyme-linked immunosorbent assay for antibodies to beta 2-glycoprotein I and a conventional anticardiolipin immunoassay. Arthritis Rheum 1996; 39: 1606-7.
38 McNally T, Purdy G, Mackie I, Machin S, Isenberg DA. The use of an anti-b2-glycoprotein 1 assay for discrimination between anticardiolipin antibodies associated with infection and increased risk of thrombosis. Br J Haematol 1995; 91: 471-3.
39 Guerin J, Smith O, White B, Sweetman G, Feighery C, Jackson J. Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorders. Br J Haematol 1998; 102: 896-902.
40 Kertesz Z, Yu BB, Steinkasserer A, Haupt H, Benham A, Sim RB. Characterization of binding of human beta 2-glycoprotein I to cardiolipin. Biochem J 1995; 310: 315-21.
41 Roubey R, Eisenberg R, Harper M, Winfield J. “Anticardiolipin” autoantibodies recognize beta 2-glycoprotein I in the absence of phospholipid Importance of Ag density and bivalent binding. J Immunol 1995; 154: 954-60.
42 Tincani A, Spatola L, Prati E, Allegri F, Ferremi P, Cattaneo R, Meroni P, Balestrieri G. The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species’ evolution. J Immunol 1996; 157: 5732-8.
43 Hunt JE, Simpson RJ, Krilis SA. Identification of a region of beta 2-glycoprotein I critical for lipid binding and anti-cardiolipin antibody cofactor activity. Proc Natl Acad Sci 1993; 90: 2141-5.
44 Martinuzzo M, Forastiero R, Carreras L. Anti beta 2 glycoprotein I antibodies: detection and association with thrombosis. Br J Haematol 1995; 89: 397-402.
45 Keeling D, Wilson A, Mackie I, Machin S, Isenberg D. Some “antiphospholipid antibodies” bind to β2-glycoprotein 1 in the absence of phospholipid. Br J Haematol 1992; 82: 571-4.
46 Cabiedes J, Cabral A, Alarcon-Segovia D. Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies. J Rheumatol 1995; 22: 1899-1906.
47 Sorice M, Circella A, Griggi T, Garofalo T, Nicodemo G, Pittoni V, Pontieri GM, Lenti L, Valesini G. Anticardiolipin and anti-beta 2-GPI are two distinct populations of autoantibodies. Thromb Haemost 1996; 75: 303-8.
48 Aoyama Y, Chan YL, Wool IG. The primary structure of rat beta 2-glycoprotein I. Nucleic Acids Res 1989; 17: 6401.
49 Sellar G, Keane J, Mehdi H, Peeples M, Browne N, Whitehead A. Characterization and acute phase modulation of canine apolipoprotein H (beta 2-glycoprotein I). Biochem Biophys Res Com 1993; 191: 1288-93.
50 Monestier M, Kandiah D, Kouts S, Novick K, Ong GL, Radic M, Krilis S. Monoclonal antibodies from NZW X BXSB F1 mice to β2-glycoprotein I and cardiolipin. J Immunol 1996; 156: 2631-41.