Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00035024.xml
Thromb Haemost 1999; 82(02): 656-661
DOI: 10.1055/s-0037-1615893
DOI: 10.1055/s-0037-1615893
Research Article
Immunology of the Antiphospholipid Syndrome: Antibodies, Antigens, and Autoimmune Response
Further Information
Publication History
Publication Date:
09 December 2017 (online)
Introduction
The antiphospholipid syndrome (APS) is an autoimmune condition in which a group of autoantibodies are thought to play a direct role in the pathogenesis of thrombosis, fetal loss, and other clinical manifestations. This review will focus on the nature of these autoantibodies, the antigens they recognize, and mechanisms that may contribute to autoimmunity and the production of autoantibodies in patients with APS.
-
References
- 1 Roubey RAS. Immunology of the antiphospholipid antibody syndrome. Arthritis Rheum 1996; 39: 1444-1454.
- 2 Harper MF, Hayes PM, Lentz BR, Roubey RAS. Characterization of β2-glycoprotein I binding to phospholipid membranes. Thromb Haemost 1998; 80: 610-614.
- 3 Bancsi LFJMM, van der Linden IK, Bertina RM. β2-glycoprotein I deficiency and the risk of thrombosis. Thromb Haemost 1992; 67: 649-653.
- 4 Takeuchi R, Yasuda S, Atsumi T, Ieko M, Takeya H, Horita T, et al. Coagulation and fibrinolytic characteristics in a β2-glycoprotein I deficiency. Lupus 1998; 7: S191.
- 5 Sheng Y, Herzog H, Krilis SA. Generation of β2-glycoprotein I gene targeting construct for disruption of the β2-GPI gene. Arthritis Rheum 1998; 41: S135.
- 6 Rojkjaer R, Klaerke DA, Schousboe I. Characterization of the interaction between β2-glycoprotein I and calmodulin, and identification of a binding sequence in β2-glycoprotein I. Biochim Biophys Acta 1997; 1339: 217-225.
- 7 Kochl S, Fresser F, Lobentanz E, Baier G, Utermann G. Novel interaction of apolipoprotein(a) with β2-glycoprotein I mediated by the kringle IV domain. Blood 1997; 90: 1482-1489.
- 8 Ma K, Zhang J-C, Wan K, Poncz M, Hajjar KA, McCrae KR. The binding of β2-glycoprotein I (β2GPI) to endothelial cells is mediated through a high affinity interaction with annexin II. Blood 1998; 92: 172A.
- 9 Del Papa N, Guidali L, Spatola L, Bonara P, Borghi MO, Tincani A, Balestrieri G, Meroni PL. Relationship between antiphospholipid and anti-endothelial cell antibodies III: β2-glycoprotein I mediates the antibody binding to endothelial membranes and induces the expression of adhesion molecules. Clin Exp Rheumatol 1995; 13: 179-185.
- 10 Simantov R, LaSala JM, Lo SK, Gharavi AE, Sammaritano LR, Salmon JE, Silverstein FL. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest 1995; 96: 2211-2219.
- 11 Shi W, Chong BH, Chesterman CN. b2-Glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. Blood 1993; 81: 1255-1262.
- 12 Price BE, Rauch J, Shia MA, Walsh MT, Lieberthal W, Gilligan HM, O’Laughlin T, Koh JS, Levine JS. Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a β2-glycoprotein I-dependent manner. J Immunol 1996; 157: 2201-2208.
- 13 Chonn A, Semple SC, Cullis PR. b2-glycoprotein I is a major protein associated with very rapidly cleared liposomes in vivo, suggesting a significant role in the immune clearance of “non-self” particles. J Biol Chem 1995; 270: 25845-25849.
- 14 Balasubramanian K, Chandra J, Schroit AJ. Immune clearance of phosphatidylserine-expressing cells by phagocytes. The role of β2-glycoprotein I in macrophage recognition. J Biol Chem 1997; 272: 31113-31117.
- 15 Arvieux J, Darnige L, Hachulla E, Roussel B, Bensa JC, Colomb MG. Species specificity of anti-b2-glycoprotein I autoantibodies and its relevance to anticardiolipin antibody quantitation. Thromb Haemost 1996; 75: 725-730.
- 16 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.
- 17 Tincani A, Spatola L, Prati E, Allegri F, Ferremi P, Cattaneo R, Meroni P, Balestrieri G. The anti- 2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native 2-glycoprotein I and preserved during species evolution. J Immunol 1996; 157: 5732-5738.
- 18 Sheng Y, Kandiah DA, Krilis SA. Anti-b2-glycoprotein I autoantibodies from patients with the “antiphospholipid” syndrome bind to β2-glycoprotein I with low affinity: dimerization of β2-glycoprotein I induces a significant increase in anti-b2-glycoprotein I antibody affinity. J Immunol 1998; 161: 2038-2043.
- 19 Ichikawa K, Khamashta MA, Koike T, Matsuura E, Hughes GRV. b2-glycoprotein I reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome. Arthritis Rheum 1994; 37: 1453-1461.
- 20 Igarashi M, Matsuura E, Igarashi Y, Nagae H, Ichikawa K, Triplett DA, Koike T. Human β2-glycoprotein I as an anticardiolipin cofactor determined using deleted mutants expressed by a baculovirus system. Blood 1996; 87: 3262-3270.
- 21 Marquis D, Victoria E, Iverson GM. β2GPI-dependent anticardiolipin autoantibodies recognize an epitope on the first domain of β2GPI. Lupus 1998; 7: S176.
- 22 McNeeley PA, Victoria EJ, Marquis D, Crisologo JF, Tuyay DC, Linnik MD. APS patient sera preferentially recognize the first domain of β2-glycoprotein I. Lupus 1998; 7: S176.
- 23 Galli M, Comfurius P, Barbui T, Zwaal RFA, Bevers EM. Anticoagulant activity of β2-glycoprotien I is potentiated by a distinct subgroup of anticardiolipin antibodies. Thromb Haemost 1992; 68: 297-300.
- 24 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: 1100-1104.
- 25 Arnout J, Wittevrongel C, Vanrusselt M, Hoylaerts M, Vermylen J. Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody beta-2-glycoprotein I complexes on phospholipid surfaces. Thromb Haemost 1998; 79: 79-86.
- 26 Willems GM, Janssen MP, Pelsers MMAL, Comfurius P, Galli M, Zwaal RFA, Bevers EM. Role of divalency in the high-affinity binding of anticardiolipin antibody-b2-glycoprotein I complexes to lipid membranes. Biochemistry 1996; 35: 13833-13842.
- 27 Takeya H, Mori T, Gabazza EC, Kuroda K, Deguchi H, Matsuura E, Ichikawa K, Koike T, Suzuki K. Anti-β2-glycoprotein I (β2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the β2GPI binding to phospholipids. J Clin Invest 1997; 99: 2260-2268.
- 28 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: 617-623.
- 29 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: 629-632.
- 30 Rao LVM, Hoang AD, Rapaport SI. Mechanisms and effects of the binding of lupus anticoagulant IgG and prothrombin to surface phospholipid. Blood 1996; 88: 4173-4182.
- 31 Arvieux J, Darnige L, Caron C, Reber G, Bensa JC, Colomb MG. Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. Thromb Haemost 1995; 74: 1120-1125.
- 32 Galli M, Beretta G, Daldossi M, Bevers EM, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. Thromb Haemost 1997; 77: 486-491.
- 33 Horbach DA, van Oort E, Derksen RH, De Groot PG. The contribution of anti-prothrombin-antibodies to lupus anticoagulant activity-discrimination between functional and non-functional anti-prothrombin-antibodies. Thromb Haemost 1998; 79: 790-795.
- 34 McNally T, Purdy G, Mackie IJ, Machin SJ, Isenberg DA. The use of an anti-b2-glycoprotein-I assay for discrimination between anticardiolipin antibodies associated with infection and increased risk of thrombosis. Br J Haematol 1995; 91: 471-473.
- 35 Guerin J, Sim RB, Feighery C, Jackson J. Antibody recognition of complement regulatory proteins, factor H, CR1 and C4BP in antiphospholipid syndrome patients. Lupus 1998; 7: S180.
- 36 Hörkkö S, Miller E, Branch DW, Palinski W, Witztum JL. The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and β2-glycoprotein I (and other proteins). Proc Natl Acad Sci USA 1997; 94: 10356-10361.
- 37 Hörkkö S, Miller E, Dudl E, Reaven P, Curtiss LK, Zvaifler NJ, Terkeltaub R, Pierangeli SS, Branch DW, Palinski W, Witztum JL. Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. J Clin Invest 1996; 98: 815-825.
- 38 Kapur A, Kelsey PR, Isaacs PE. Factor V inhibitor in thrombosis. Am J Hematol 1993; 42: 384-388.
- 39 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: 2618-2625.
- 40 Pengo V, Biasiolo A, Brocco T, Tonetto S, Ruffatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies. Thromb Haemost 1996; 75: 721-724.
- 41 Carson CW, Comp PC, Esmon NL, Rezaie AR, Esmon CT. Thrombomodulin antibodies inhibit protein C activation and are found in patients with lupus anticoagulant and unexplained thrombosis. Arthritis Rheum 1994; 37: S296.
- 42 Matsuda J, Saitoh N, Gohchi K, Gotoh M, Tsukamoto M. Antiannexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody. Am J Hematol 1994; 47: 56-58.
- 43 Shibata S, Sasaki T, Harpel P, Fillit H. Autoantibodies to vascular heparan sulfate proteoglycan in systemic lupus erythematosus react with endothelial cells and inhibit the formation of thrombinantithrombin III complexes. Clin Immunol Immunopathol 1994; 70: 114-123.
- 44 Moore JE, Mohr CF. Biologically false positive serologic tests for syphilis. JAMA 1952; 150: 467-473.
- 45 Moore JE, Lutz WB. The natural history of systemic lupus erythematosus: an approach to its study through chronic biologic false positive reactors. J Chron Dis 1955; 1: 297-316.
- 46 Mujic F, Cuadrado MJ, Lloyd M, Khamashta MA, Page G, Hughes GR. Primary antiphospholipid syndrome evolving into systemic lupus erythematosus. J Rheumatol 1995; 22: 1589-1592.
- 47 Derksen RHWM, Gmelig-Meijling FH, De Groot PG. Primary antiphospholipid syndrome evolving into systemic lupus erythematosus. Lupus 1996; 5: 77-80.
- 48 Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 1994; 179: 1317-1330.
- 49 Smith HR, Hansen CL, Rose R, Canoso RT. Autoimmune MRL-lpr/lpr mice are an animal model for the secondary APS. J Rheumatol 1990; 17: 911-915.
- 50 Hashimoto Y, Kawamura M, Ichikawa K, Suzuki T, Sumida T, Yoshida S, Matsuura E, Ikehara S, Koike T. Anticardiolipin antibodies in NZW x BXSB F1 mice: a model of antiphospholipid antibody syndrome. J Immunol 1992; 149: 1063-1068.
- 51 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. J Immunol 1996; 2631-2641.
- 52 Tincani A, Beltrami B, Meroni PL, Allegri F, Spatola L, Cinquini M, et al. Immunization of naive BALB/c mice with human β2-glycoprotein I (β2GPI) breaks tolerance against the murine molecule. Lupus 1998; 7: S173.
- 53 Levine JS, Subang R, Koh JS, Rauch J. Induction of antiphospholipid autoantibodies by β2-glycoprotein I bound to apoptotic thymocytes. J Autoimmun 1998; 11: 413-424.
- 54 Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of antiphospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci USA 1991; 88: 3069-3073.
- 55 Blank M, Krause I, Lanir N, Vardi P, Gilburd B, Tincani A, Tomer Y, Shoenfeld Y. Transfer of experimental antiphospholipid-syndrome by bone marrow cell transplantation: the importance of the T cell. Arthritis Rheum 1995; 38: 115-122.
- 56 Adachi Y, Inaba M, Sugihara A, Koshiji M, Sugiura K, Amoh Y, Mori S, Kamiya T, Genba H, Ikehara S. Effects of administration of monoclonal antibodies (anti-CD4 or anti-CD8) on the development of autoimmune diseases in (NZW x BXSB)F1 mice. Immunobiology 1998; 198: 451-464.
- 57 Arnett FC, Olsen ML, Anderson KL, Reveille JD. Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant. J Clin Invest 1991; 87: 1490-1495.
- 58 Sebastiani GD, Galeazzi M, Morozzi G, Marcolongo R. The immunogenetics of the antiphospholipid syndrome, anticardiolipin antibodies, and lupus anticoagulant. Semin Arthritis Rheum 1996; 25: 414-420.
- 59 Goel N, Ortel TL, Bali D, Anderson J, Gourley IS, Smith H, Morris CA, DeSimone M, Branch DW, Ford P, Berdeaux D, Roubey RA, Kostyu DD, Kingsmore SF, Thiel T, Amos C, Seldin MF. Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance. Arthritis Rheum. In press
- 60 Ida A, Hirose S, Hamano Y, Kodera S, Jiang Y, Abe M, Zhang D, Nishimura H, Shirai T. Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW x BXSB) F1 mice. Eur J Immunol 1998; 28: 2694-2703.
- 61 Ibnou-Zekri N, Iwamoto M, Fossati L, McConahey PJ, Izui S. Role of the major histocompatibility complex class II Ea gene in lupus susceptibility in mice. Proc Natl Acad Sci USA 1997; 94: 14654-14659.
- 62 Fossati L, Iwamoto M, Merino R, Izui S. Selective enhancing effect of the Yaa gene on immune responses against self and foreign antigens. Eur J Immunol 1995; 25: 166-173