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Molecular Autoimmunity pp 377–391Cite as

Molecular Pathogenesis of the Antiphospholipid Syndrome: Toward Novel Therapeutic Targets

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References

  • Amengual, O., Atsumi, T., Khamashta, M.A., and Hughes, G.R.V. (1998). The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb. Haemost., 79, 276–281.

    CAS  PubMed  Google Scholar 

  • Borsch-Haubold, A.G., Ghomashchi, F., Pasquet, S., Goedert, M., Cohen, P., Gelb, M.H., and Watson, S.P. (1999). Phosphorylation of cytosolic phospholipase A2 in platelets is mediated by multiple stress-activated protein kinase pathways. Eur. J. Biochem., 265, 195–203.

    Article  CAS  PubMed  Google Scholar 

  • Branch, D.W., Dudley, D.J., Mitchell, M.D., Creighton, K.A., Abbott, T.M., Hammond, E.H., and Daynes, R.A. (1990). Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: A model for autoimmune fetal loss. Am. J. Obstet. Gynecol., 163, 210–216.

    CAS  PubMed  Google Scholar 

  • Buschbeck, M., Ghomashchi, F., Gelb, M.H., Watson, S.P., and Borsch-Haubold, A.G. (1999). Stress stimuli increase calcium-induced arachidonic acid release through phosphorylation of cytosolic phospholipase A2. Biochem. J., 344, 359–366.

    Article  CAS  PubMed  Google Scholar 

  • Campbell, A.L., Pierangeli, S.S., Wellhausen, S., and Harris, E.N. (1995). Comparison of the effect of anticardiolipin antibodies from patients with the antiphospholipid syndrome and with syphilis on platelet activation and aggregation. Thromb. Haemost., 73, 529–534.

    CAS  PubMed  Google Scholar 

  • Cohen, P. (1997). The search for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell. Biol., 7, 353–358.

    Article  CAS  Google Scholar 

  • Crowther, M.A., Ginsberg, J.S., Julian, J., Denburg, J., Hirsch, J., Douketis, J., Laskin, C., Fortin, P., Anderson, D., Kearon, C., Clarke, A., Geerts, W., Forgie, M., Green, D., Costantini, L., Yacura, W., Wilson, S., Gent, M., and Kovacs, M.J. (2003). A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N. Engl. J. Med., 349, 1133–1138.

    Article  CAS  PubMed  Google Scholar 

  • Davis, W.D. and Brey, R.L. (1992). Antiphospholipid antibodies and complement activation in patients with cerebral ischemia. Clin. Exp. Immunol., 10, 455–460.

    CAS  Google Scholar 

  • Del Papa, N., Sheng, Y.H., Raschi, E., Kandiah, D.A., Tincani, A., Khamashta, M.A., Atsumi, T., Hughes, G.R., Ichikawa, K., Koike, T., Balestrieri, G., Krilis, S.A., and Meroni, P.L. (1998). Human β2-glycoprotein I binds to endothelial cells through a cluster of lysine residues that are critical for anionic phospholipids binding and offers epitopes for anti-β2glycoprotein I antibodies. J. Immunol., 160, 5572–5578.

    PubMed  Google Scholar 

  • Edwards, M.H., Pierangeli, S., Liu, X.W., Barker, J.H., Anderson, G., and Harris, E.N. (1997). Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation, 96, 4380–4384.

    CAS  PubMed  Google Scholar 

  • Esmon, N.L., Safa, O., Smirnov, M., and Esmon, C.T. (2000). Antiphospholipid antibodies and the protein C pathway. J. Autoimmun., 15, 221–225.

    CAS  PubMed  Google Scholar 

  • Espinola, R.G., Pierangeli, S.S., Gharavi, A.E., and Harris, E.N. (2002). Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb. Haemost., 87, 518–522.

    CAS  PubMed  Google Scholar 

  • Eto, M. and Luscher, T.F. (2003). Modulation of coagulation and fibrinolytic pathways by statins. Endothelium, 10(1), 35–41.

    Article  CAS  PubMed  Google Scholar 

  • Ferguson, J.J., Kereiakes, D.J., Adgey, A.A., Fox, K.A., Hillegass, W.B., Jr., Pfisterer, M., Vassanelli, C. (1998). Safe use of GPIIb/IIIa inhibitors. Eur. Heart J., Suppl. D40-51. Review.

    Google Scholar 

  • Ferrara, D.E., Liu, X., Espinola, R.G., Meroni, P.L., Abukhalaf, I., Harris, E.N., and Pierangeli, S.S. (2003). Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum., 48(11), 3272–3279.

    Article  CAS  PubMed  Google Scholar 

  • Ferrara, D.E., Swerlick, R., Casper, K., Meroni, P.L., Vega-Ostertag, M., Harris, E.N., and Pierangeli, S.S. (2004). Fluvastatin inhibits upregulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. J. Thromb. Haemost., 2, 1558–1563.

    Article  CAS  PubMed  Google Scholar 

  • Forastiero, R., Martinuzzo, M., Carreras, L.O., and Maclouf, J. (1998). Anti-β2glycoprotein I antibodies and platelet activation in patients with antiphospholipid antibodies: Association with increased excretion of platelet-derived thromboxane urinary metabolites. Thromb. Haemost., 79, 42–45.

    CAS  PubMed  Google Scholar 

  • Gharavi, A.E., Pierangeli, S.S., Colden-Stanfield, M., Liu, X.W., Espinola, R.G., and Harris, E.N. (1999). GDKV-induced antiphospholipid antibodies enhance thrombosis and activate endothelial cells in vivo and in vitro. J. Immunol., 163, 2922–2927.

    CAS  PubMed  Google Scholar 

  • Girardi, G., Berman, J., Redecha, P., Spruce, L., Thruman, J.M., Kraus, D., Hollmann, T., Casali, P., Caroll, M.C., Wetsel, R.A., Lambris, J.D., Holers, M., and Salmon, J.E. (2003). Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J. Clin. Invest., 112, 1644–1654.

    Article  CAS  PubMed  Google Scholar 

  • Harris, E.N. (1987). Syndrome of the black swan. Br. J. Rheumatol., 26, 324–326.

    CAS  PubMed  Google Scholar 

  • Hattori, E., Hamilton, K.K., McEver, R.P., and Sims, P.J. (1989). Complement proteins C5b-9 induce secretion of high molecular weight multimers of endothelial von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J. Biol. Chem., 264, 9053–9060.

    CAS  PubMed  Google Scholar 

  • Holers, V.M., Girardi, G., Mo, L., Guthridge, J.M., Molina, H., Pierangeli, S.S., Espinola, R.G., Liu, X., Mao, D., Vialpando, C.G., and Salmon, J.E. (2002). Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J. Exp. Med., 195, 211–220.

    Article  CAS  PubMed  Google Scholar 

  • Jankowski, M., Vreys, I., Wittevrongel, C., Boon, D., Vermylen, J., Hoyaerts, M.F., and Arnout, J. (2003). Thrombogenicity of β2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood, 101, 157–162.

    Article  CAS  PubMed  Google Scholar 

  • Johnson, R. and Charnley, J. (1979). Hydroxychloroquine in prophylaxis of pulmonary embolism following hip arthroplasty. Orthop. Clin., 144, 174–177.

    Google Scholar 

  • Khamashta, M.A., Cuadrado, M.J., Mujic, T., Taub, N.A., Hunt, B.M., and Hughes, G.R.V. (1995). The management of thrombosis in the antiphospholipid antibody syndrome. N. Engl. J. Med., 332, 993–997.

    Article  CAS  PubMed  Google Scholar 

  • Krnic-Barrie, S., O’Connor, C.R., Looney, S.W., Pierangeli, S.S., and Harris, E.N. ((1997). A retrospective review of 61 patients with antiphospholipid syndrome. Arch. Intern. Med., 157, 2101–2108.

    Article  CAS  PubMed  Google Scholar 

  • Kwak, B., Mulhaupt, F., Myit, S., and Mach, F. (2000). Statins as a newly recognized type of immunomodulator. Nat. Med., 6, 1399–1402.

    CAS  PubMed  Google Scholar 

  • Lee, J.C., Kumar, S., Griswold, D.E., Underwood, D.C., Votta, B.J., and Adamas, J.L. (2000). Inhibition of p38 MAPK as a therapeutic strategy. Immunopharmacology, 47, 185.

    Article  CAS  PubMed  Google Scholar 

  • Lin, Y.L. and Wang, C.T. (1992). Activation of human platelets by the rabbit anticardiolipin antibodies. Blood, 80, 3135–3143.

    CAS  PubMed  Google Scholar 

  • Ma, K., Simantov, R., Zhang, J.C., Silverstein, R., Hajjar, K.A., and McCrae, K.R. (2000). Highaffinity binding of β2 glycoprotein I to human endothelial cells is mediated by annexin II. J. Biol. Chem., 275(20), 15541–15548.

    Article  CAS  PubMed  Google Scholar 

  • Martinuzzo, M.E., Maclouf, J., Carreras, L.O., and Levy-Toledano, S. (1993). Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation. Thromb. Haemost., 70, 667–671.

    CAS  PubMed  Google Scholar 

  • Meroni, P.L., Raschi, E., Camera, M., Testoni, C., Nicoletti, F., Tincani, A., Khamashta, M.A., Balestrieri, G., Tremoli, E., and Hess, D.C. (2000). Endothelial activation by aPL: A Potential pathogenetic mechanism for the clinical manifestations of the syndrome. J. Autoimmun., 30, 237–240.

    Google Scholar 

  • Meroni, P.L., Raschi, E., Testoni, C., Tincani, A., Balestrieri, G., Molteni, R., Khamashta, M.A., Tremoli, E., and Camera, M. (2001). Statins prevent endothelial cell activation induced by antiphospholipid (anti-β2-glycoprotein I) antibodies: Effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum., 44, 2870–2878.

    Article  CAS  PubMed  Google Scholar 

  • Meroni, P.L. and Riboldi, P. (2001). Pathogenic mechanisms mediating antiphospholipid syndrome. Curr. Opin. Rheumatol., 13, 377–382.

    Article  CAS  PubMed  Google Scholar 

  • Munakata, Y., Saito, T., Matsuda, K., Serina, J., Shibata, S., and Sasaki, T. (2000). Detection of complement-fixing antiphospholipid antibodies in association with thrombosis. Thromb. Haemost., 83, 728–731.

    CAS  PubMed  Google Scholar 

  • Nadal-Wollbold, F., Pawlowski, M., Levy-Toledano, S., Berrou, E., Rosa, J.P., and Bryckaert, M. (2002). Platelet ERK2 activation by thrombin is dependent on calcium and conventional protein kinases C but not Raf-1 or B-Raf, FEBS Lett., 531(3), 475–482.

    Article  CAS  PubMed  Google Scholar 

  • Nemerson, Y. (1988). Tissue factor and hemostasis. Blood, 71, 1–8.

    CAS  PubMed  Google Scholar 

  • Niwa, S., Totsuka, T., and Hayashi, S. (1996). Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor on the expression of adhesion molecules on human monocyte cell line. Int. J. Immunopharmacol., 18, 669–675.

    Article  CAS  PubMed  Google Scholar 

  • Opara, R., Robbins, D.L., and Ziboh, V.A. (2003). Cyclic-AMP agonists inhibit antiphospholipid/β2 glycoprotein I induced synthesis of human platelet thromboxane A2 in vitro. J. Rheumatol., 30, 55–58.

    CAS  PubMed  Google Scholar 

  • Osterud, B. and Bjorklid, E. (2001). The tissue factor pathway in disseminated intravascular coagulation. Semin. Thromb. Haemost., 27, 605–617.

    CAS  Google Scholar 

  • Petri, M. (1996). Thrombosis and systemic lupus erythematosus: The Hopkins lupus cohort perspective. Scand. J. Rheumatol., 25, 91–193.

    Google Scholar 

  • Pierangeli, S.S., Colden-Stanfield, M., Liu, X., Barker, J.H., Anderson, G.H., and Harris, E.N. (1999). Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation, 99, 1997–2000.

    CAS  PubMed  Google Scholar 

  • Pierangeli, S.S., Espinola, R.G., Liu, X., and Harris, E.N. (2001). Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Circ. Res., 88, 245–250.

    CAS  PubMed  Google Scholar 

  • Pierangeli, S.S., Girardi, G., Vega-Ostertag, M.E., Liu, X., Espinola, R.G., Salmon, J.E. (2005). Requirement of activation of complement C3 and C5 for antiphospholipid-antibody-mediated thrombophilia. Arthritis Rheum. 52, 1545–1554.

    Article  PubMed  Google Scholar 

  • Pierangeli, S.S., Liu, X.W., Anderson, G.H., Barker, J.H., and Harris, E.N. (1995). Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome. Thromb. Haemost., 74, 1361–1367.

    CAS  PubMed  Google Scholar 

  • Pierangeli, S.S., Vega-Ostertag, M., and Harris, E.N. (2004). Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: A pathway to targeted therapies. Thromb. Res., 114, 467–476.

    Article  CAS  PubMed  Google Scholar 

  • Quigg, R.J. (2002). Use of complement inhibitors in tissue injury. Trends Mol. Med., 8, 430–436.

    Article  CAS  PubMed  Google Scholar 

  • Raschi, E., Testoni, C., Bosisio, D., Borghi, M.O., Koike, T., Mantovani, A., and Meroni, P.L. (2003). The role of MYD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood, 101(9), 3495–3500.

    Article  CAS  PubMed  Google Scholar 

  • Robbins, D.L., Leung, S., Miller-Blair, D.J., and Ziboh, V. (1998). Effect of anticardiolipin/β2 glycoprotein I complexes on production of thromboxane A2 by platelets from patients with the antiphospholipid syndrome. J. Rheumatol., 25(1), 51–56.

    CAS  PubMed  Google Scholar 

  • Roubey, R.A.S. (1998). Mechanisms of autoantibody-mediated thrombosis. Lupus, 7, S114–S119.

    CAS  PubMed  Google Scholar 

  • Salmon, J.E., Girardi, G., and Holers, V.M. (2002). Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann. Rheum. Dis., 61, 46–50.

    Google Scholar 

  • Semerato, N. and Colucci, M. (1997). Tissue factor in health and disease. Thromb. Haemost., 78, 759–764.

    Google Scholar 

  • Shin, M.L., Ros, H.G., and Nicolescu, F.I. (1996). Membrane attack by complement assembly and biology of terminal complement complexes. Biomembranes, 4, 123–149.

    CAS  Google Scholar 

  • Shoenfeld, Y. and Blank, M. (1994). Effect of long-acting thromboxane receptor antagonist (BMS180,291) on experimental antiphospholipid syndrome. Lupus, 3, 397–400.

    CAS  PubMed  Google Scholar 

  • Simantov, R., Lo, S.K., Gharavi, A., Sammaritano, L.R., Salmon, J.E., and Silverstein, R.L. (1996). Antiphospholipid antibodies activate vascular endothelial cells. Lupus, 5, 440–441.

    CAS  PubMed  Google Scholar 

  • Vega-Ostertag, M.E., Harris, E.N., and Pierangeli, S.S. (2004). Inracellular events in platelet activation induced by antiphospholipid antibodies in the presence of low doses of thrombis. Arthritis Rheum., 50, 2911–2919.

    Article  CAS  PubMed  Google Scholar 

  • Vega-Ostertag, M., Kasper, K., Swerlick, R., Ferrara, D.E., Harris, E.N., and Pierangeli, S.S. (2005). P38 mitogen activated protein kinase is involved in upregulation of tissue factor by antiphospholipid antibodies, Arthritis Rheum. 52, 1545–1554.

    Article  CAS  PubMed  Google Scholar 

  • Wang, L., Su, C.-Y., Chou, K.-Y., and Wang, C.T. (2002). Enhancement of human platelet activation by the combination of low concentrations of collagen and rabbit anticardiolipin antibodies. Br. J. Haematol., 118, 1152–1162.

    CAS  PubMed  Google Scholar 

  • Wetsel, R.A. (1995). Structure, function and cellular expression of complement anaphylotoxin receptors. Curr. Opin. Immunol., 7, 48–53.

    Article  CAS  PubMed  Google Scholar 

  • Wilson, W.A., Gharavi, A.E., Koike, T., Lockshin, M.D., Branch, D.W., Piette, J.C., Brey, R., Derksen, R., Triplett, D.A., Harris, E.N., Hughes, G.R., and Khamashta, M.A. (1999). International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: Report of an international workshop. Arthritis Rheum., 42, 1309–1311.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia

    Silvia S. Pierangeli & Mariano Vega-Ostertag

  2. Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia

    Azzudin E. Gharavi

  3. Univ of the West Indies, Mona 7, Kingston, Jamaica

    E. Nigel Harris (Vice-chancellor)

Authors
  1. Silvia S. Pierangeli
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  2. Mariano Vega-Ostertag
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  3. Azzudin E. Gharavi
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  4. E. Nigel Harris
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Editors and Affiliations

  1. Institut National de Santé et de Recherche Médicale (INSERM), Paris, France

    Moncef Zouali

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Pierangeli, S.S., Vega-Ostertag, M., Gharavi, A.E., Harris, E.N. (2005). Molecular Pathogenesis of the Antiphospholipid Syndrome: Toward Novel Therapeutic Targets. In: Zouali, M. (eds) Molecular Autoimmunity. Springer, Boston, MA. https://doi.org/10.1007/0-387-24534-0_26

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