The significance of autoantibodies against β2-glycoprotein I

Blood

Volumn 120, Issue 2, 2012, Pages 266-274

  De Groot, Philip G ^a   Urbanus, Rolf T ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITHROMBOCYTIC AGENT; ANTIVITAMIN K; AUTOANTIBODY; BETA1 GLYCOPROTEIN 1 ANTIBODY; CARDIOLIPIN ANTIBODY; HEPARIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN M; LIPOCORTIN 2; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 8; MEMBRANE PROTEIN; PHOSPHOLIPID; PHOSPHOLIPID ANTIBODY; PLASMIN; PREGNANCY SPECIFIC BETA1 GLYCOPROTEIN; PROTEIN H; TIFI PROTEIN; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 8; UNCLASSIFIED DRUG;

ADENOVIRUS; ALLELE; ANTIBODY DETECTION; ANTIBODY SPECIFICITY; ANTIGEN BINDING; ANTIPHOSPHOLIPID SYNDROME; B LYMPHOCYTE; BLEEDING; BLOOD VESSEL INJURY; BORRELIA BURGDORFERI; CELL MATURATION; CHLAMYDOPHILA PSITTACI; COXIELLA BURNETII; CRYSTAL STRUCTURE; CYTOMEGALOVIRUS; DISEASE ASSOCIATION; ENDOTHELIUM CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; EPSTEIN BARR VIRUS; ESCHERICHIA COLI; FETUS WASTAGE; GENE MUTATION; GENETIC VARIABILITY; HELICOBACTER PYLORI; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN PARVOVIRUS B19; HUMAN T CELL LEUKEMIA VIRUS 1; LEISHMANIA; LEPTOSPIROSIS; MONOCYTE; MYCOBACTERIUM LEPRAE; MYCOBACTERIUM TUBERCULOSIS; MYCOPLASMA PNEUMONIAE; NONHUMAN; PATHOPHYSIOLOGY; PLACENTA INSUFFICIENCY; PLASMODIUM FALCIPARUM; PREGNANCY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN INTERACTION; RECURRENCE RISK; REVIEW; RICKETTSIA TYPHI; RISK; SALMONELLA TYPHI; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PYOGENES; SYNCYTIOTROPHOBLAST; T LYMPHOCYTE; THROMBOSIS; THROMBOSIS PREVENTION; TRANSMISSION ELECTRON MICROSCOPY; VARICELLA ZOSTER VIRUS;

EID: 84864150391     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-03-378646     Document Type: Review

References (116)

1. McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. 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 U S A. 1990;87(11):4120-4124.
2. Galli M, Comfurius P, Maassen C, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet. 1990;335(8705):1544-1547. (Pubitemid 20189625)
3. Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet. 1990;336(8708):177-178. (Pubitemid 20225005)
4. Bouma B, de Groot PG, van den Elsen JM, et al. Adhesion mechanism of human beta(2)- glycoprotein I to phospholipids based on its crystal structure. EMBO J. 1999;18(19):5166-5174. (Pubitemid 29465567)
5. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
6. Chamley LW, McKay EJ, Pattison NS. Cofactor dependent and cofactor independent anticardiolipin antibodies. Thromb Res. 1991;61(3):291-299.
7. Oosting JD, Derksen RH, Entjes HT, Bouma BN, de Groot PG. Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I. Thromb Haemost. 1992;67(5):499-502.
8. Roubey RA, Pratt CW, Buyon JP, Winfield JB. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. J Clin Invest. 1992;90(3):1100-1104.
9. Bevers EM, Galli M, Barbui T, Comfurius P, Zwaal RF. Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost. 1991;66(6):629-632.
10. de Laat B, Derksen RH, Urbanus RT, de Groot PG. IgG antibodies that recognize epitope Gly40- Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood. 2005;105(4):1540-1545. (Pubitemid 40223671)
11. De Laat B, Derksen RH, Reber G, et al. An international multicentre-laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti-beta2- glycoprotein autoantibodies. J Thromb Haemost. 2011;9(1):149-153.
12. Pierangeli SS, Chen PP, Raschi E, et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost. 2008;34(3):236-250.
13. Arad A, Proulle V, Furie RA, Furie BC, Furie B. Beta-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model. Blood. 2011;117(12):3453-3459.
14. McNeil HP, Chesterman CN, Krilis SA. Binding specificity of lupus anticoagulants and anticardiolipin antibodies. Thromb Res. 1988;52(6):609-619. (Pubitemid 19028232)
15. Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101(5):1827-1832. (Pubitemid 36237580)
16. Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de Groot PG, Algra A. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009; 8(11):998-1005.
17. Lockshin MD, Kim M, Laskin CA, et al. Lupus anticoagulant, but not anticardiolipin antibody, predicts adverse pregnancy outcome in patients with antiphospholipid antibodies [prepublished online ahead of print January 24, 2012]. Arthritis Rheum. doi:10.1002/art.34402.
18. Brey RL, Abbott RD, Curb JD, et al. Beta(2)- glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu heart program. Stroke. 2001;32(8):1701-1706. (Pubitemid 32772193)
19. Palosuo T, Virtamo J, Haukka J, et al. High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men-a nested case-control study. Thromb Haemost. 1997;78(4):1178-1182. (Pubitemid 27464582)
20. Iverson GM, Victoria EJ, Marquis DM. Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci U S A. 1998;95(26):15542-15546. (Pubitemid 29018735)
21. de Laat B, Derksen RH, van Lummel M, Pennings MT, de Groot PG. Pathogenic anti-beta2- glycoprotein I antibodies recognize domain I of beta2-glycoprotein I only after a conformational change. Blood. 2006;107(5):1916-1924. (Pubitemid 43289372)
22. Ioannou Y, Pericleous C, Giles I, Latchman DS, Isenberg DA, Rahman A. Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43. Arthritis Rheum. 2007;56(1):280-290. (Pubitemid 46106202)
23. Forastiero R, Martinuzzo M, de Larranaga G, Vega-OstertagM, Pierangeli S. Anti-beta2glycoprotein I antibodies from leprosy patients do not show thrombogenic effects in an in vivo animal model. J Thromb Haemost. 2011;9(4):859-861.
24. Andreoli L, Nalli C, Motta M, et al. Anti-beta-glycoprotein I IgG antibodies from 1-year-old healthy children born to mothers with systemic autoimmune diseases preferentially target domain 4/5: might it be the reason for their 'innocent' profile? Ann Rheum Dis. 2011;70(2):380-383.
25. Ioannou Y, Romay-Penabad Z, Pericleous C, et al. In vivo inhibition of antiphospholipid antibody-induced pathogenicity utilizing the antigenic target peptide domain I of beta2-glycoprotein I: proof of concept. J Thromb Haemost. 2009;7(5):833-842.
26. Pengo V, Ruffatti A, Legnani C, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118(17):4714- 4718.
27. Dienava-Verdoold I, Boon-Spijker MG, de Groot PG, et al. Patient-derived monoclonal antibodies directed towards beta2 glycoprotein-1 display lupus anticoagulant activity. J Thromb Haemost. 2011;9(4):738-747.
28. Urbanus RT, de Groot PG. Antiphospholipid antibodies- we are not quite there yet. Blood Rev. 2011;25(2):97-106.
29. Reber G, Schousboe I, Tincani A, et al. Interlaboratory variability of anti-beta2-glycoprotein I measurement. A collaborative study in the frame of the european forum on antiphospholipid antibodies standardization group. Thromb Haemost. 2002;88(1):66-73. (Pubitemid 34752269)
30. Brighton TA, Dai YP, Hogg PJ, Chesterman CN. Microheterogeneity of beta-2 glycoprotein I: implications for binding to anionic phospholipids. Biochem J. 1999;340(Pt 1):59-67. (Pubitemid 29251091)
31. Ruffatti A, Tonello M, Visentin MS, et al. Risk factors for pregnancy failure in patients with antiphospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology (Oxford). 2011;50(9):1684-1689.
32. Mehrani T, Petri M. Association of IgA anti-beta2 glycoprotein I with clinical and laboratory manifestations of systemic lupus erythematosus. J Rheumatol. 2011;38(1):64-68.
33. Sweiss NJ, Bo R, Kapadia R, et al. IgA anti-beta2- glycoprotein I autoantibodies are associated with an increased risk of thromboembolic events in patients with systemic lupus erythematosus. PLoS One. 2010;5(8):e12280.
34. Samarkos M, Davies KA, Gordon C, Loizou S. Clinical significance of IgA anticardiolipin and anti-beta2-GP1 antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Clin Rheumatol. 2006;25(2):199-204. (Pubitemid 43372318)
35. Mehrani T, Petri M. IgM anti-beta2 glycoprotein I is protective against lupus nephritis and renal damage in systemic lupus erythematosus. J Rheumatol. 2011;38(3):450-453.
36. Sène D, Piette JC, Cacoub P. Antiphospholipid antibodies, antiphospholipid syndrome and infections. Autoimmun Rev. 2008;7(4):272-277.
37. Biggioggero M, Meroni PL. The geoepidemiology of the antiphospholipid antibody syndrome. Autoimmun Rev. 2010;9(5):A299-304.
38. Cucnik S, Kveder T, Ulcova-Gallova Z, et al. The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the european forum on antiphospholipid antibodies. Lupus. 2011;20(11):1166-1171.
39. de Laat B, Derksen RH, de Groot PG. High-avidity anti-beta glycoprotein I antibodies highly correlate with thrombosis in contrast to low-avidity anti-beta glycoprotein I antibodies. J Thromb Haemost. 2006;4(7):1619-1621.
40. Kouts S, Wang MX, Adelstein S, Krilis SA. Immunization of a rabbit with beta 2-glycoprotein I induces charge-dependent crossreactive antibodies that bind anionic phospholipids and have similar reactivity as autoimmune antiphospholipid antibodies. J Immunol. 1995;155(2):958-966.
41. Gharavi AE, Pierangeli SS, Espinola RG, Liu X, Colden-Stanfield M, Harris EN. Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum. 2002;46(2):545-552. (Pubitemid 34136593)
42. Blank M, Krause I, Fridkin M, et al. Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Invest. 2002;109(6):797-804. (Pubitemid 34263156)
43. Krause I, Blank M, Cervera R, et al. Cross-reactive epitopes on beta2-glycoprotein-I and Saccharomyces cerevisiae in patients with the antiphospholipid syndrome. Ann N Y Acad Sci. 2007;1108:481-488. (Pubitemid 47528762)
44. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999;42(7):1309-1311. (Pubitemid 30265586)
45. Delbos V, Abgueguen P, Chennebault JM, Fanello S, Pichard E. Acute cytomegalovirus infection and venous thrombosis: role of antiphospholipid antibodies. J Infect. 2007;54(1): e47-e50. (Pubitemid 44932954)
46. Albert LJ, Inman RD. Molecular mimicry and autoimmunity. N Engl J Med. 1999;341(27):2068-2074. (Pubitemid 30035957)
47. Sherer Y, Blank M, Shoenfeld Y. Antiphospholipid syndrome (APS): where does it come from? Best Pract Res Clin Rheumatol. 2007;21(6):1071-1078. (Pubitemid 350194039)
48. Gotoh M, Matsuda J. Induction of anticardiolipin antibody and/or lupus anticoagulant in rabbits by immunization with lipoteichoic acid, lipopolysaccharide and lipid A. Lupus. 1996;5(6):593-597. (Pubitemid 27035729)
49. Subang R, Levine JS, Janoff AS, et al. Phospholipid-bound beta 2-glycoprotein I induces the production of anti-phospholipid antibodies. J Autoimmun. 2000;15(1):21-32. (Pubitemid 32289459)
50. Uthman IW, Gharavi AE. Viral infections and antiphospholipid antibodies. Semin Arthritis Rheum. 2002;31(4):256-263. (Pubitemid 34160809)
51. Blank M, Shoenfeld Y. Beta-2-glycoprotein-I, infections, antiphospholipid syndrome and therapeutic considerations. Clin Immunol. 2004;112(2):190-199. (Pubitemid 38881485)
52. Merrill JT. Do antiphospholipid antibodies develop for a purpose? Curr Rheumatol Rep. 2006;8(2):109-113. (Pubitemid 44623978)
53. Jordö ED, Wermeling F, Chen Y, Karlsson MC. Scavenger receptors as regulators of natural antibody responses and B cell activation in autoimmunity. Mol Immunol. 2011;48(11):1307-1318.
54. von Landenberg P, Doring Y, Modrow S, Lackner KJ. Are antiphospholipid antibodies an essential requirement for an effective immune response to infections? Ann N Y Acad Sci. 2007;1108:578-583. (Pubitemid 47528771)
55. Kra-Oz Z, Lorber M, Shoenfeld Y, Scharff Y. Inhibitor(s) of natural anti-cardiolipin autoantibodies. Clin Exp Immunol. 1993;93(2):265-268. (Pubitemid 23238038)
56. Dighiero G, Rose NR. Critical self-epitopes are key to the understanding of self-tolerance and autoimmunity. Immunol Today. 1999;20(9):423-428. (Pubitemid 29423485)
57. Lieby P, Soley A, Knapp AM, et al. Memory B cells producing somatically mutated antiphospholipid antibodies are present in healthy individuals. Blood. 2003;102(7):2459-2465. (Pubitemid 37193583)
58. Fleming SD, Egan RP, Chai C, et al. Antiphospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice. J Immunol. 2004;173(11):7055-7061. (Pubitemid 39541095)
59. Fleming SD, Pope MR, Hoffman SM, et al. Domain V peptides inhibit beta2-glycoprotein I-mediated mesenteric ischemia/reperfusion-induced tissue damage and inflammation. J Immunol. 2010;185(10):6168-6178.
60. McIntyre JA, Wagenknecht DR. Antiphospholipid antibodies and renal transplantation: a risk assessment. Lupus. 2003;12(7):555-559. (Pubitemid 36890150)
61. Balasubramanian K, Schroit AJ. Characterization of phosphatidylserine- dependent beta2-glycoprotein I macrophage interactions. Implications for apoptotic cell clearance by phagocytes. J Biol Chem. 1998; 273(44):29272-29277. (Pubitemid 28507629)
62. Abdel-Monem H, Dasgupta SK, Le A, Prakasam A, Thiagarajan P. Phagocytosis of platelet microvesicles and beta2- glycoprotein I. Thromb Haemost. 2010;104(2):335-341.
63. Shi W, Krilis SA, Chong BH, Gordon S, Chesterman CN. Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population. Aust N Z J Med. 1990;20(3):231-236. (Pubitemid 20283041)
64. Cheng HM, Chamley L. Cryptic natural autoantibodies and co-potentiators. Autoimmun Rev. 2008;7(6):431-434.
65. McIntyre JA, Wagenknecht DR, Faulk WP. Redox-reactive autoantibodies: detection and physiological relevance. Autoimmun Rev. 2006;5(1):76-83. (Pubitemid 41759446)
66. Hasselaar P, Triplett DA, LaRue A, et al. Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA. J Rheumatol. 1990;17(2):186-191. (Pubitemid 20108221)
67. Ag? ar C, de Groot PG, Marquart JA, Meijers JC. Evolutionary conservation of the lipopolysaccharide binding site of beta-glycoprotein I. Thromb Haemost. 2011;106(6):1069-1075.
68. Agar C, van Os GM, Morgelin M, et al. Beta2- glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood. 2010;116(8):1336-1343.
69. Kuwana M, Matsuura E, Kobayashi K, et al. Binding of beta 2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells. Blood. 2005;105(4):1552-1557. (Pubitemid 40223674)
70. van Os GM, Meijers JC, Agar C, et al. Induction of anti-beta2- glycoprotein I autoantibodies in mice by protein H of streptococcus pyogenes. J Thromb Haemost. 2011;9(12):2447-2456.
71. de Laat B, van Berkel M, Urbanus RT, et al. Immune responses against domain I of beta(2)- glycoprotein I are driven by conformational changes: domain I of beta(2)-glycoprotein I harbors a cryptic immunogenic epitope. Arthritis Rheum. 2011;63(12):3960-3968.
72. Chamorro AJ, Marcos M, Miron-Canelo JA, Cervera R, Espinosa G. Val247Leu beta2- glycoprotein-I allelic variant is associated with antiphospholipid syndrome: systematic review and meta-analysis [prepublished online ahead of print January 8, 2012]. Autoimmun Rev. doi: 10.1016/j.autrev.2011.12.006.
73. Yasuda S, Atsumi T, Matsuura E, et al. Significance of valine/leucine247 polymorphism of beta2-glycoprotein I in antiphospholipid syndrome: Increased reactivity of anti-beta2-glycoprotein I autoantibodies to the valine247 beta2-glycoprotein I variant. Arthritis Rheum. 2005;52(1):212-218. (Pubitemid 40129250)
74. Ioannou Y, Zhang JY, Passam FH, et al. Naturally occurring free thiols within beta 2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress-induced cell injury. Blood. 2010;116(11):1961-1970.
75. Ioannou Y, Zhang JY, Qi M, et al. Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen beta2-glycoprotein I. Arthritis Rheum. 2011;63(9):2774-2782.
76. Romay-Penabad Z, Aguilar-Valenzuela R, Urbanus RT, et al. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood. 2011;117(4):1408-1414.
77. Ramesh S, Morrell CN, Tarango C, et al. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via beta2GPI and apoER2. J Clin Invest. 2011;121(1):120-131.
78. Fischetti F, Durigutto P, Pellis V, et al. Thrombus formation induced by antibodies to beta2-glycoprotein I is complement dependent and requires a priming factor. Blood. 2005;106(7):2340-2346. (Pubitemid 41510805)
79. Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002; 46(4):1019-1027. (Pubitemid 34303815)
80. Krone KA, Allen KL, McCrae KR. Impaired fibrinolysis in the antiphospholipid syndrome. Curr Rheumatol Rep. 2010;12(1):53-57.
81. Urbanus RT, de Laat B. Antiphospholipid antibodies and the protein C pathway. Lupus. 2010;19(4):394-399.
82. Boles J, Mackman N. Role of tissue factor in thrombosis in antiphospholipid antibody syndrome. Lupus. 2010;19(4):370-378.
83. Ambrozic A, Bozic B, Kveder T, et al. Budding, vesiculation and permeabilization of phospholipid membranes-evidence for a feasible physiologic role of beta2-glycoprotein I and pathogenic actions of anti-beta2-glycoprotein I antibodies. Biochim Biophys Acta. 2005;1740(1):38-44. (Pubitemid 40692696)
84. Satta N, Dunoyer-Geindre S, Reber G, et al. The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies. Blood. 2007;109(4):1507-1514. (Pubitemid 46239583)
85. Raschi E, Testoni C, Bosisio D, et al. Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood. 2003;101(9):3495-3500. (Pubitemid 36857933)
86. Allen KL, Fonseca FV, Betapudi V, Willard B, Zhang J, McCrae KR. A novel pathway for human endothelial cell activation by antiphospholipid/anti-beta2 glycoprotein I antibodies. Blood. 2012;119(3):884-893.
87. Döring Y, Hurst J, Lorenz M, et al. Human antiphospholipid antibodies induce TNFalpha in monocytes via toll-like receptor 8. Immunobiology. 2010;215(3):230-241.
88. Ma K, Simantov R, Zhang JC, Silverstein R, Hajjar KA, McCrae KR. High affinity binding of beta 2-glycoprotein I to human endothelial cells is mediated by annexin II. J Biol Chem. 2000;275(20):15541-15548. (Pubitemid 30337288)
89. Shi T, Giannakopoulos B, Yan X, et al. Anti-beta2- glycoprotein I antibodies in complex with beta2-glycoprotein I can activate platelets in a dysregulated manner via glycoprotein ib-IX-V. Arthritis Rheum. 2006;54(8):2558-2567. (Pubitemid 44205017)
90. Pennings MT, Derksen RH, van Lummel M, et al. Platelet adhesion to dimeric beta-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein ibalpha and apolipoprotein E receptor 2′. J Thromb Haemost. 2007;5(2):369-377. (Pubitemid 46139463)
91. Lutters BC, Derksen RH, Tekelenburg WL, Lenting PJ, Arnout J, de Groot PG. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2′. J Biol Chem. 2003;278(36):33831-33838. (Pubitemid 37553217)
92. Pierangeli SS, Vega-Ostertag ME, Raschi E, et al. Toll-like receptor and antiphospholipid mediated thrombosis: in vivo studies. Ann Rheum Dis. 2007;66(10):1327-1333. (Pubitemid 47492476)
93. Romay-Penabad Z, Montiel-Manzano MG, Shilagard T, et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood. 2009;114(14):3074-3083.
94. Di Simone N, Meroni PL, de Papa N, et al. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2- glycoprotein I. Arthritis Rheum. 2000;43(1):140-150. (Pubitemid 30368223)
95. Di Simone N, Raschi E, Testoni C, et al. Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro. Ann Rheum Dis. 2005;64(3):462-467. (Pubitemid 40283060)
96. Van Horn JT, Craven C, Ward K, Branch DW, Silver RM. Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes. Placenta. 2004;25(7):642-648. (Pubitemid 38950318)
97. Out HJ, Kooijman CD, Bruinse HW, Derksen RH. Histopathological findings in placentae from patients with intra-uterine fetal death and antiphospholipid antibodies. Eur J Obstet Gynecol Reprod Biol. 1991;41(3):179-186.
98. Rand JH, Wu XX, Quinn AS, Taatjes DJ. The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: role in pregnancy losses and thrombosis. Lupus. 2010;19(4):460-469.
99. Girardi G, Berman J, Redecha P, et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003;112(11):1644-1654. (Pubitemid 38063722)
100. Jankowski M, Vreys I, Wittevrongel C, et al. Thrombogenicity of beta 2-glycoprotein Idependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood. 2003;101(1):157-162. (Pubitemid 36025902)
101. Pierangeli SS, Girardi G, Vega-Ostertag M, Liu X, Espinola RG, Salmon J. Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum. 2005;52(7):2120-2124. (Pubitemid 40994335)
102. Holers VM, Girardi G, Mo L, et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med. 2002;195(2):211-220. (Pubitemid 34461265)
103. Iverson GM, Reddel S, Victoria EJ, et al. Use of single point mutations in domain I of beta 2- glycoprotein I to determine fine antigenic specificity of antiphospholipid autoantibodies. J Immunol. 2002;169(12):7097-7103. (Pubitemid 36899298)
104. 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(2):653-659.
105. Horbach DA, van Oort E, Tempelman MJ, Derksen RH, de Groot PG. The prevalence of a non-phospholipid-binding form of beta2- glycoprotein I in human plasma-consequences for the development of anti-beta2-glycoprotein I antibodies. Thromb Haemost. 1998;80(5):791-797.
106. Guerin J, Sheng Y, Reddel S, Iverson GM, Chapman MG, Krilis SA. Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivation of this blood protein. Elucidation of the consequences of the two biological events in patients with the anti-phospholipid syndrome. J Biol Chem. 2002;277(4):2644-2649. (Pubitemid 34953290)
107. de la Torre YM, Pregnolato F, D'Amelio F, et al. Anti-phospholipid induced murine fetal loss: novel protective effect of a peptide targeting the beta2 glycoprotein I phospholipid-binding site. Implications for human fetal loss. J Autoimmun. 2012;38:J209-J215.
108. Ostertag MV, Liu X, Henderson V, Pierangeli SS. A peptide that mimics the vth region of beta- 2-glycoprotein I reverses antiphospholipid-mediated thrombosis in mice. Lupus. 2006;15(6):358-365. (Pubitemid 44032711)
109. van Lummel M, Pennings MT, Derksen RH, et al. The binding site in {beta}2-glycoprotein I for ApoER2′ on platelets is located in domain V. J Biol Chem. 2005;280(44):36729-36736. (Pubitemid 41587752)
110. Lee CJ, De Biasio A, Beglova N. Mode of interaction between beta2GPI and lipoprotein receptors suggests mutually exclusive binding of beta2GPI to the receptors and anionic phospholipids. Structure. 2010;18(3):366-376.
111. Kolyada A, Lee CJ, De Biasio A, Beglova N. A novel dimeric inhibitor targeting beta2GPI in Beta2GPI/antibody complexes implicated in antiphospholipid syndrome. PLoS One. 2010;5(12):e15345.
112. Urbanus RT, Pennings MT, Derksen RH, de Groot PG. Platelet activation by dimeric beta2- glycoprotein I requires signaling via both glycoprotein ibalpha and apolipoprotein E receptor 2′. J Thromb Haemost. 2008;6(8):1405-1412. (Pubitemid 352016322)
113. Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008;112(5):1687-1695.
114. Rand JH, Wu XX, Quinn AS, et al. Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood. 2010;115(11):2292-2299.
115. Edwards MH, Pierangeli S, Liu X, Barker JH, Anderson G, Harris EN. Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation. 1997;96(12):4380-4384. (Pubitemid 28007469)
116. Prowse C, Pepper D, Dawes J. Prevention of the platelet alpha-granule release reaction by membrane-active drugs. Thromb Res. 1982;25(3):219-227. (Pubitemid 12192388)