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Autoimmunity Highlights
Erschienen in: Autoimmunity Highlights 2/2011

01.11.2011 | Review Article

Pathophysiology of the antiphospholipid antibody syndrome

verfasst von: Rohan Willis, Silvia S. Pierangeli

Erschienen in: Autoimmunity Highlights | Ausgabe 2/2011

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Abstract

Antiphospholipid antibodies (aPL) are associated with the recurrent pregnancy loss and thrombosis that characterizes the antiphospholipid antibody syndrome (APS). Although the ontogeny of these pathogenic antibodies has not been fully elucidated, there is evidence that indicates the involvement of both genetic and environmental factors. The ability of aPL to induce a procoagulant phenotype in APS patients plays a central role in the development of arterial and venous thrombotic manifestations typical of the disease. Inflammation serves as a necessary link between this procoagulant phenotype and actual thrombus development and is an important mediator of the placental injury seen in APS patients with obstetric complications. Recent evidence has indicated a role for abnormal cellular proliferation and differentiation in the pathophysiology of APS, especially in those patients with pregnancy morbidity and other more atypical manifestations that have no identifiable thrombotic cause. The interplay of genetic and environmental factors responsible for aPL development and the mechanisms by which these antibodies produce disease in APS patients is the focus of this review.
Literatur
1.
Harris EN (1987) Syndrome of the black swan. Br J Rheumatol 26:324–326PubMed
2.
Wilson WA, Ghavari AE, Koike T et al (1999) International concensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 42:1309–1311PubMed
3.
Miyakis S, Lockshin MD, Atsumi I et al (2006) International concensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306PubMed
4.
McNeil HP, Simpson RJ, Cherterman CN et al (1990) Antiphospholipid antibodies are directed against a complex antigen that includes lipid binding inhibitor of coagulation: β2 glycoprotein I (apolipoprotein H). Proc Natl Acad Sci USA 87:4120–4124PubMedPubMedCentral
5.
Galli M, Comfurius P, Maassen C et al (1990) Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 335(8705):1544–1547PubMed
6.
Amengual O, Atsumi T, Koike T (2004) Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome. Clin Immunol 112(2):144–149PubMed
7.
Permpikul P, Rao LV, Rapaport SI (1994) Functional and binding studies of the roles of prothrombin and beta 2-glycoprotein I in the expression of lupus anticoagulant activity. Blood 83(10):2878–2892PubMed
8.
Chen PP, Giles I (2010) Antibodies to serine proteases in the antiphospholipid syndrome. Curr Rheumatol Rep 12(1):45–52PubMedPubMedCentral
9.
Cesarman-Maus G, Ríos-Luna NP, Deora AB et al (2006) Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome. Blood 107(11):4375–4382PubMedPubMedCentral
10.
Rand JH, Wu XX, Quinn AS, Taatjes DJ (2008) Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome. Lupus 17(10):922–930PubMed
11.
Boey ML et al (1983) Thrombosis in SLE: striking association with the presence of circulating lupus anticoagulant. Br Med J 287:101–102
12.
Ginsburg KS, Liang MH, Newcomer L et al (1992) Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 117:997–1002PubMed
13.
McClain MT, Arbuckle MR, Heinlen LD et al (2004) The prevalence, onset and clinical significance of antiphospholipid antibodies prior to diagnosis of systemic lupus erythematosus. Arthritis Rheum 50:1226–1232PubMed
14.
Petri M (2010) Update on anti-phospholipid antibodies in SLE: the Hopkins’ Lupus Cohort. Lupus 19:419–423PubMed
15.
Asherson RA (2005) Multiorgan failure and antiphospholipid antibodies: the catastrophic antiphospholipid (Asherson’s) syndrome. Immunobiology 210:727–733PubMed
16.
Tincani A, Balestieri G, Danieli E et al (2003) Pregnancy complications of the antiphospholipid syndrome. Autoimmunity 36:27–32PubMed
17.
Levine JS, Branch DW, Rauch J (2002) The antiphospholipid syndrome N Engl J Med 346:752–763
18.
Sailer T, Zaglami C, Kurz C et al (2006) Anti-beta(2)-glycoprotein-I antibodies are associated with pregnancy loss in women with the lupus anticoagulant. Thromb Haemost 5:796–801
19.
Erkan D, Lockshin MD (2010) Non-criteria manifestations of antiphospholipid syndrome. Lupus 19:424–427PubMed
20.
Cervera R, Piette JC, Font J et al (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1, 000 patients. Arthritis Rheum 46:1019–1027PubMed
21.
Galli M, Finazzi G, Barbui T (1996) Thrombocytopenia in the antiphospholipid syndrome. Br J Hematol 93:1–5
22.
Harris EN, Asherson RA, Hughes GR (1988) Antiphospholipid antibodies–autoantibodies with a difference. Annu Rev Med 39:261–271PubMed
23.
Gharavi AE, Pierangeli SS (1998) Origin of antiphospholipid antibodies: induction of aPL by viral peptides. Lupus 7(Suppl 2):S52–S54PubMed
24.
Sherer Y, Blank M, Shoenfeld Y (2007) Antiphospholipid syndrome (APS): where does it come from? Best Pract Res Clin Rheumatol 21(6):1071–1078PubMed
25.
Meroni PL, Raschi E, Camera M et al (2000) Endothelial activation by aPL: a potential pathogenetic mechanism for the clinical manifestations of the syndrome. J Autoimmun 15(2):237–240PubMed
26.
Urbanus RT, Derksen RH, de Groot PG (2008) Platelets and the antiphospholipid syndrome. Lupus 17(10):888–894PubMed
27.
Nojima J, Suehisa E, Kuratsune H et al (1999) Platelet activation induced by combined effects of anticardiolipin and lupus anticoagulant IgG antibodies in patients with systemic lupus erythematosus—possible association with thrombotic and thrombocytopenic complications. Thromb Haemost 81(3):436–441PubMed
28.
Krone KA, Allen KL, McCrae KR (2010) Impaired fibrinolysis in the antiphospholipid syndrome. Curr Rheumatol Rep 12(1):53–57PubMedPubMedCentral
29.
Horstman LL, Jy W, Bidot CJ et al (2009) Antiphospholipid antibodies: paradigm in transition. J Neuroinflammation 6:3PubMedPubMedCentral
30.
D’Ippolito S, Di Simone N, Di Nicuolo F et al (2007) Antiphospholipid antibodies: effects on trophoblast and endothelial cells. Am J Reprod Immunol 58(2):150–158PubMed
31.
Di Simone N, Luigi MP, Marco D et al (2007) Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature. Ann N Y Acad Sci 1108:505–514PubMed
32.
33.
Ames PR, Antinolfi I, Ciampa A et al (2008) Primary antiphospholipid syndrome: a low-grade auto-inflammatory disease? Rheumatology (Oxford) 47(12):1832–1837
34.
Abrahams VM (2009) Mechanisms of antiphospholipid antibody-associated pregnancy complications. Thromb Res 124(5):521–525PubMed
35.
Sebastiani GD, Galeazzi M (2009) Genetic aspects of the antiphospholipid syndrome: HLA associations. Handbook of systemic autoimmune diseases. Antiphospholipid Syndrome Syst Autoimmune Dis 10:81–89
36.
Castro-Marrero J, Balada E, Vilardell-Tarrés M et al (2009) Genetic risk factors of thrombosis in the antiphospholipid syndrome. Br J Haematol 147(3):289–296PubMed
37.
Gharavi AE, Pierangeli SS, Harris EN (2001) Origin of antiphospholipid antibodies. Rheum Dis Clin North Am 27(3):551–563PubMed
38.
Gharavi AE, Pierangeli SS, Harris EN (2003) Viral origin of antiphospholipid antibodies: endothelial cell activation and thrombus enhancement by CMV peptide-induced APL antibodies. Immunobiology 207(1):37–42PubMed
39.
Hashimoto Y, Kawamura M, Ichikawa K et al (1992) Anticardiolipin antibodies in NZW × BXSB F1 mice. A model of antiphospholipid syndrome. J Immunol 149(3):1063–1068PubMed
40.
Hang LM, Izui S, Dixon FJ (1981) (NZW × BXSB)F1 hybrid. A model of acute lupus and coronary vascular disease with myocardial infarction. J Exp Med 154(1):216–221PubMed
41.
Oyaizu N, Yasumizu R., Miyama-Inaba M, Nomura S, Yoshida H, Miyama S, Shibata Y, Mitsuoka S, Yasunaga K, Mori S, Good RA, Ikehara S (1988) (NZW × BXSB) F1 mouse, a new animal model of idlopathic thrombocytopenic purpura. J Exp Med 167(6):2017–2022
42.
Kita Y, Sumida T, Iwamoto I, Yoshida S, Koike T (1994) V gene analysis of anti-cardiolipin antibodies from (NZW × BXSB) F1 mice. Immunology 82(3):494–501PubMedPubMedCentral
43.
Ida A, Hirose S, Hamano Y et al (1998) Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW × BXSB) F1 mice. Eur J Immunol 28(9):2694–2703PubMed
44.
Izui S, Masuda K, Yoshida H (1984) Acute SLE in F1 hybrids between SB/Le and NZW mice: Prominently enhanced formation of gp70 immune complexes by a Y chromosome-associated factor from SB/Le mice. J Immunol 132:701–710PubMed
45.
Izui S, Higaki M, Morrow D, Merino R (1988) The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW × C57BL/6)F1 male mice, but not in C57BL/6 male mice. Eur J Immunol 18(6):911–915PubMed
46.
Gharavi AE, Mellors RC, Elkon KB (1989) IgG anti-cardiolipin antibodies in murine lupus. Clin Exp Immunol 78(2):233–238PubMedPubMedCentral
47.
Kita Y, Sumida T, Ichikawa K, Maeda T, Yonaha F, Iwamoto I, Yoshida S, Koike T (1994) V gene analysis of anticardiolipin antibodies from MRL-lpr/lpr mice
48.
Ahmed SA, Verthelyi D (1993) Antibodies to cardiolipin in normal C57BL/6 J mice: induction by estrogen but not dihydrotestosterone. J Autoimmun 6(3):265–279PubMed
49.
Verthelyi D, Ansar Ahmed S (1997) Characterization of estrogen-induced autoantibodies to cardiolipin in non-autoimmune mice. J Autoimmun 10(2):115–125PubMed
50.
Harvey AM, Shulman LE (1966) Connective tissue disease and the chronic biologic false-positive test for syphilis (BFP reaction). Med Clin North Am 50(5):1271–1279PubMed
51.
Exner T, Barber S, Kronenberg H, Rickard KA (1980) Familial association of the lupus anticoagulant. Br J Haematol 45(1):89–96PubMed
52.
Jolidon RM, Knecht H, Humair L, de Torrente A (1991) Different clinical presentations of a lupus anticoagulant in the same family. Klin Wochenschr 69(8):340–344PubMed
53.
Matthey F, Walshe K, Mackie IJ, Machin SJ (1989) Familial occurrence of the antiphospholipid syndrome. J Clin Pathol 42(5):495–497PubMedPubMedCentral
54.
Mackworth-Young C, Chan J, Harris N et al (1987) High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus. J Rheumatol 14(4):723–726PubMed
55.
Goldberg SN, Conti-Kelly AM, Greco TP (1995) A family study of anticardiolipin antibodies and associated clinical conditions. Am J Med 99(5):473–479PubMed
56.
Goel N, Ortel TL, Bali D et al (1999) Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance. Arthritis Rheum 42(2):318–327PubMed
57.
Dagenais P, Urowitz MB, Gladman DD, Norman CS (1992) A family study of the antiphospholipid syndrome associated with other autoimmune diseases. J Rheumatol 19(9):1393–1396PubMed
58.
Rouget JP, Goudemand J, Montreuil G et al (1982) Lupus anticoagulant: a familial observation. Lancet 2(8289):105PubMed
59.
Mackie IJ, Colaco CB, Machin SJ (1987) Familial lupus anticoagulants. Br J Haematol 67(3):359–363PubMed
60.
May KP, West SG, Moulds J, Kotzin BL (1993) Different manifestations of the antiphospholipid antibody syndrome in a family with systemic lupus erythematosus. Arthritis Rheum 36(4):528–533PubMed
61.
Arnett FC, Olsen ML, Anderson KL, Reveille JD (1991) Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant. J Clin Invest 87(5):1490–1495PubMedPubMedCentral
62.
Asherson RA, Doherty DG, Vergani D et al (1992) Major histocompatibility complex associations with primary antiphospholipid syndrome. Arthritis Rheum 35(1):124–125PubMed
63.
Caliz R, Atsumi T, Kondeatis E et al (2001) HLA class II gene polymorphisms in antiphospholipid syndrome: haplotype analysis in 83 Caucasoid patients. Rheumatology (Oxford) 40(1):31–36
64.
Bertolaccini ML, Atsumi T, Caliz AR et al (2000) Association of antiphosphatidylserine/prothrombin autoantibodies with HLA class II genes. Arthritis Rheum 43(3):683–688PubMed
65.
Vargas-Alarcon G, Granados J, Bekker C et al (1995) Association of HLA-DR5 (possibly DRB1*1201) with the primary antiphospholipid syndrome in Mexican patients. Arthritis Rheum 38(9):1340–1341PubMed
66.
Galeazzi M, Sebastiani GD, Tincani A et al (2000) HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus. Lupus 9(1):47–55PubMed
67.
Hashimoto H, Yamanaka K, Tokano Y et al (1998) HLA-DRB1 alleles and beta 2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic lupus erythematosus. Clin Exp Rheumatol 16(4):423–427PubMed
68.
Arnett FC, Thiagarajan P, Ahn C, Reveille JD (1999) Associations of anti-beta2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups. Arthritis Rheum 42(2):268–274PubMed
69.
Wilson WA, Perez MC, Michalski JP, Armatis PE (1988) Cardiolipin antibodies and null alleles of C4 in black Americans with systemic lupus erythematosus. J Rheumatol 15(12):1768–1772PubMed
70.
Wilson WA, Scopelitis E, Michalski JP et al (1995) Familial anticardiolipin antibodies and C4 deficiency genotypes that coexist with MHC DQB1 risk factors. J Rheumatol 22(2):227–235PubMed
71.
Petri M, Watson R, Winkelstein JA, McLean RH (1993) Clinical expression of systemic lupus erythematosus in patients with C4A deficiency. Medicine (Baltimore) 72(4):236–244
72.
Hirose N, Williams R, Alberts AR et al (1999) A role for the polymorphism at position 247 of the beta2-glycoprotein I gene in the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome. Arthritis Rheum 42(8):1655–1661PubMed
73.
Atsumi T, Tsutsumi A, Amengual O et al (1999) Correlation between beta2-glycoprotein I valine/leucine247 polymorphism and anti-beta2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome. Rheumatology (Oxford) 38(8):721–723
74.
Prieto GA, Cabral AR, Zapata-Zuñiga M et al (2003) Valine/valine genotype at position 247 of the beta2-glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies. Arthritis Rheum 48(2):471–474PubMed
75.
Reverter JC, Tassies MD (2009) Genetic aspects of the antiphospholipid syndrome: associations with clinical manifestations. Handbook of Systemic Autoimmune Diseases. Antiphospholipid Syndrome in Systemic Autoimmune Disease 10:91–103
76.
Rees DC, Cox M, Clegg JB (1995) World distribution of factor V Leiden. Lancet 346(8983):1133–1134PubMed
77.
Franco RF, Elion J, Tavella MH et al (1999) The prevalence of factor V Arg306– > Thr (factor V Cambridge) and factor V Arg306– > Gly mutations in different human populations. Thromb Haemost 81(2):312–313PubMed
78.
Schütt M, Klüter H, Hagedorn-Greiwe M et al (1998) Familial coexistence of primary antiphospholipid syndrome and factor V Leiden. Lupus 7(3):176–182PubMed
79.
Brenner B, Vulfsons SL, Lanir N, Nahir M (1996) Coexistence of familial antiphospholipid syndrome and factor V Leiden: impact on thrombotic diathesis. Br J Haematol 94(1):166–167PubMed
80.
Chopra N, Koren S, Greer WL et al (2002) Factor V Leiden, prothrombin gene mutation, and thrombosis risk in patients with antiphospholipid antibodies. J Rheumatol 29(8):1683–1688PubMed
81.
Bentolila S, Ripoll L, Drouet L et al (1997) Lack of association between thrombosis in primary antiphospholipid syndrome and the recently described thrombophilic 3′-untranslated prothrombin gene polymorphism. Thromb Haemost 78(5):1415PubMed
82.
Bertolaccini ML, Atsumi T, Hunt BJ et al (1998) Prothrombin mutation is not associated with thrombosis in patients with antiphospholipid syndrome. Thromb Haemost 80(1):202–203PubMed
83.
Ruiz-Argüelles GJ, Garcés-Eisele J, Ruiz-Delgado GJ, Alarcón-Segovia D (1999) The G20210A polymorphism in the 3′-untranslated region of the prothrombin gene in Mexican mestizo patients with primary antiphospholipid syndrome. Clin Appl Thromb Hemost 5(3):158–160PubMed
84.
Sivera P, Bosio S, Bertero MT et al (2000) G20210A homozygosity in antiphospholipid syndrome secondary to systemic lupus erythematosus. Haematologica 85(1):109–110PubMed
85.
de Visser MC, Rosendaal FR, Bertina RM (1999) A reduced sensitivity for activated protein C in the absence of factor V Leiden increases the risk of venous thrombosis. Blood 93(4):1271–1276PubMed
86.
Erkan D, Zhang HW, Shriky RC, Merrill JT (2002) Dual antibody reactivity to beta2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome. Lupus 11(4):215–220PubMed
87.
Ames PR, Margaglione M, Tommasino C et al (2001) Impact of plasma homocysteine and prothrombin G20210 A on primary antiphospholipid syndrome. Blood Coagul Fibrinolysis 12(8):699–704PubMed
88.
Lincz LF, Adams MJ, Scorgie FE et al (2007) Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden. Blood Coagul Fibrinolysis 18(6):559–564PubMed
89.
Jiménez S, Tàssies D, Espinosa G et al (2008) Double heterozygosity polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa increases arterial thrombosis and arteriosclerosis in patients with the antiphospholipid syndrome or with systemic lupus erythematosus. Ann Rheum Dis 67(6):835–840PubMed
90.
Yasuda S, Tsutsumi A, Atsumi T et al (2002) Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies. J Rheumatol 29(6):1192–1197PubMed
91.
Diz-Kucukkaya R, Hancer VS, Inanc M et al (2004) Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome. Lupus 13(1):32–35PubMed
92.
de Laat B, Derksen RH, Mackie IJ et al (2006) Annexin A5 polymorphism (-1C– > T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome. Ann Rheum Dis 65(11):1468–1472PubMedPubMedCentral
93.
Diz-Kucukkaya R, Inanc M, Afshar-Kharghan V et al (2007) P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome. Ann Rheum Dis 66(10):1378–1380PubMedPubMedCentral
94.
de la Red G, Tàssies D, Espinosa G et al (2009) Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels. Thromb Haemost 101(2):312–316
95.
Bugert P, Pabinger I, Stamer K et al (2007) The risk for thromboembolic disease in lupus anticoagulant patients due to pathways involving P-selectin and CD154. Thromb Haemost 97(4):573–580PubMed
96.
Bertolaccini ML, Atsumi T, Lanchbury JS et al (2001) Plasma tumor necrosis factor alpha levels and the -238*A promoter polymorphism in patients with antiphospholipid syndrome. Thromb Haemost 85(2):198–203PubMed
97.
Pierangeli SS, Vega-Ostertag ME, Raschi E et al (2007) Toll-like receptor and antiphospholipid mediated thrombosis: in vivo studies. Ann Rheum Dis 66(10):1327–1333PubMedPubMedCentral
98.
Gharavi AE, Sammaritano LR, Wen J, Elkon KB (1992) Induction of antiphospholipid autoantibodies by immunization with beta 2 glycoprotein I (apolipoprotein H). J Clin Invest 90(3):1105–1109PubMedPubMedCentral
99.
Gharavi AE, Pierangeli SS, Colden-Stanfield M et al (1999) GDKV-induced antiphospholipid antibodies enhance thrombosis and activate endothelial cells in vivo and in vitro. J Immunol 163(5):2922–2927PubMed
100.
Gharavi AE, Pierangeli SS, Gharavi EE et al (1998) Thrombogenic properties of antiphospholipid antibodies do not depend on their binding to beta2 glycoprotein 1 (beta2GP1) alone. Lupus 7(5):341–346PubMed
101.
Gharavi EE, Chaimovich H, Cucurull E et al (1999) Induction of antiphospholipid antibodies by immunization with synthetic viral and bacterial peptides. Lupus 8(6):449–455PubMed
102.
Gharavi AE, Pierangeli SS, Espinola RG et al (2002) Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo. Arthritis Rheum 46(2):545–552PubMed
103.
Gharavi AE, Vega-Ostertag M, Espinola RG et al (2004) Intrauterine fetal death in mice caused by cytomegalovirus-derived peptide induced aPL antibodies. Lupus 13(1):17–23PubMed
104.
Blank M, Krause I, Fridkin M et al (2002) Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Invest 109(6):797–804PubMedPubMedCentral
105.
Levy Y, Almog O, Gorshtein A, Shoenfeld Y (2006) The environment and antiphospholipid syndrome. Lupus 15(11):784–790PubMed
106.
Wasserman A (1907) Über Entwicklung und den Gegenwartingen Stand der Serodiagnostic gegenüber Syphilis, Berl. Klin Wochenschr 44:1599–1634
107.
Harris EN, Gharavi AE, Boey ML et al (1983) Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 2(8361):1211–1214PubMed
108.
Uthman IW, Gharavi AE (2002) Viral infections and antiphospholipid antibodies. Semin Arthritis Rheum 31(4):256–263PubMed
109.
Sène D, Piette JC, Cacoub P (2009) Antiphospholipid antibodies, antiphospholipid syndrome and viral infections. Rev Med Int 30(2):135–141
110.
van de Berg PJ, Heutinck KM, Raabe R et al (2010) Human cytomegalovirus induces systemic immune activation characterized by a type 1 cytokine signature. J Infect Dis 202(5):690–699PubMed
111.
Prandota J (2003) Possible pathomechanism of autoimmune hepatitis. Am J Ther 10(1):51–57PubMed
112.
Nakagawa K, Harrison LC (1996) The potential roles of endogenous retroviruses in autoimmunity. Immunol Rev 152:193–236PubMed
113.
Molina V, Shoenfeld Y (2005) Infection, vaccines and other environmental triggers of autoimmunity. Autoimmunity 38(3):235–245PubMed
114.
Martinuc Porobic J, Avcin T, Bozic B et al (2005) Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine. Clin Exp Immunol 142(2):377–380PubMedPubMedCentral
115.
Uetrecht J (2005) Current trends in drug-induced autoimmunity. Autoimmun Rev 4(5):309–314PubMed
116.
Lillicrap DP, Pinto M, Benford K et al (1990) Heterogeneity of laboratory test results for antiphospholipid antibodies in patients treated with chlorpromazine and other phenothiazines. Am J Clin Pathol 93(6):771–775PubMed
117.
Tincani A, Taraborelli M, Cattaneo R (2010) Antiphospholipid antibodies and malignancies. Autoimmun Rev 9(4):200–202PubMed
118.
Palomo I, Segovia F, Ortega C, Pierangeli S (2009) Antiphospholipid syndrome: a comprehensive review of a complex and multisystemic disease. Clin Exp Rheumatol 27(4):668–677PubMed
119.
Miyakis S, Giannakopoulos B, Krilis SA (2004) Beta 2 glycoprotein I—function in health and disease. Thromb Res 114(5–6):335–346PubMed
120.
Shoenfeld Y, Blank M, Cervera R et al (2006) Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis 65(1):2–6PubMedPubMedCentral
121.
Harris EN, Asherson RA, Gharavi AE et al (1985) Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody. Br J Haematol 59(2):227–230PubMed
122.
Lellouche F, Martinuzzo M, Said P et al (1991) Imbalance of thromboxane/prostacyclin biosynthesis in patients with lupus anticoagulant. Blood 78(11):2894–2899PubMed
123.
Khamashta MA, Harris EN, Gharavi AE et al (1988) Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes. Ann Rheum Dis 47(10):849–854PubMedPubMedCentral
124.
Lutters BC, Derksen RH, Tekelenburg WL et al (2003) Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2′. J Biol Chem 278(36):33831–33838PubMed
125.
Espinola RG, Pierangeli SS, Gharavi AE, Harris EN (2002) Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 87(3):518–522PubMed
126.
Pierangeli SS, Vega-Ostertag M, Harris EN (2004) Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to targeted therapies. Thromb Res 114(5–6):467–476PubMed
127.
Shi T, Giannakopoulos B, Yan X et al (2006) 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 54(8):2558–2567PubMed
128.
Urbanus RT, Pennings MT, Derksen RH, de Groot PG (2008) Platelet activation by dimeric beta2-glycoprotein I requires signaling via both glycoprotein Ibalpha and apolipoprotein E receptor 2’. J Thromb Haemost 6(8):1405–1412PubMed
129.
Sikara MP, Routsias JG, Samiotaki M et al (2010) {beta}2 Glycoprotein I ({beta}2GPI) binds platelet factor 4 (PF4): implications for the pathogenesis of antiphospholipid syndrome. Blood 115(3):713–723PubMed
130.
Pierangeli SS, Colden-Stanfield M, Liu X et al (1999) Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation 99(15):1997–2002PubMed
131.
Meroni PL, Raschi E, Camera M et al (2000) Endothelial activation by aPL: a potential pathogenetic mechanism for the clinical manifestations of the syndrome. J Autoimmun 15(2):237–240PubMed
132.
Simantov R, Lo SK, Gharavi A et al (1996) Antiphospholipid antibodies activate vascular endothelial cells. Lupus 5(5):440–441PubMed
133.
Pierangeli SS, Espinola RG, Liu X, Harris EN (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(2):245–250PubMed
134.
Amengual O, Atsumi T, Khamashta MA, Hughes GR (1998) The role of the tissue factor pathway in the hypercoagulable state in patients with the antiphospholipid syndrome. Thromb Haemost 79(2):276–281PubMed
135.
Kornberg A, Blank M, Kaufman S, Shoenfeld Y (1994) Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol 153(3):1328–1332PubMed
136.
Reverter JC, Tàssies D, Font J et al (1998) Effects of human monoclonal anticardiolipin antibodies on platelet function and on tissue factor expression on monocytes. Arthritis Rheum 41(8):1420–1427PubMed
137.
Alijotas-Reig J, Palacio-Garcia C, Vilardell-Tarres M (2009) Circulating microparticles, lupus anticoagulant and recurrent miscarriages. Eur J Obstet Gynecol Reprod Biol 145(1):22–26PubMed
138.
Cuadrado MJ, Buendía P, Velasco F et al (2006) Vascular endothelial growth factor expression in monocytes from patients with primary antiphospholipid syndrome. J Thromb Haemost 4(11):2461–2469PubMed
139.
Raschi E, Testoni C, Bosisio D et al (2003) Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood 101(9):3495–3500PubMed
140.
Vega-Ostertag ME, Ferrara DE, Romay-Penabad Z et al (2007) Role of p38 mitogen-activated protein kinase in antiphospholipid antibody-mediated thrombosis and endothelial cell activation. J Thromb Haemost 5(9):1828–1834PubMed
141.
Jajoria P, Murthy V, Papalardo E, Romay-Penabad Z, Gleason C, Pierangeli SS (2009) Statins for the treatment of antiphospholipid syndrome? Ann N Y Acad Sci 1173:736–745PubMed
142.
Fischetti F, Durigutto P, Pellis V et al (2005) Thrombus formation induced by antibodies to beta2-glycoprotein I is complement dependent and requires a priming factor. Blood 106(7):2340–2346PubMed
143.
Zhang J, McCrae KR (2005) Annexin A2 mediates endothelial cell activation by antiphospholipid/anti-beta2 glycoprotein I antibodies. Blood 105(5):1964–1969PubMed
144.
Romay-Penabad Z, Montiel-Manzano MG, Shilagard T, Papalardo E et al (2009) Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 114(14):3074–3083PubMed
145.
Sorice M, Longo A, Capozzi A et al (2007) Anti-beta2-glycoprotein I antibodies induce monocyte release of tumor necrosis factor alpha and tissue factor by signal transduction pathways involving lipid rafts. Arthritis Rheum 56(8):2687–2697PubMed
146.
Lambrianides A, Carroll CJ, Pierangeli SS et al (2010) Effects of polyclonal IgG derived from patients with different clinical types of the antiphospholipid syndrome on monocyte signaling pathways. J Immunol 184(12):6622–6628PubMedPubMedCentral
147.
Satta N, Dunoyer-Geindre S, Reber G et al (2007) The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies. Blood 109(4):1507–1514PubMed
148.
Verstak B, Nagpal K, Bottomley SP et al (2009) MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses. J Biol Chem 284(36):24192–24203PubMedPubMedCentral
149.
Alard JE, Gaillard F, Daridon C et al (2010) TLR2 is one of the endothelial receptors for beta 2-glycoprotein I. J Immunol 185(3):1550–1557PubMed
150.
Döring Y, Hurst J, Lorenz M et al (2010) Human antiphospholipid antibodies induce TNFalpha in monocytes via Toll-like receptor 8. Immunobiology 215(3):230–241PubMed
151.
Hurst J, Prinz N, Lorenz M et al (2009) TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells. Immunobiology 214(8):683–691PubMed
152.
Raschi E, Broggini V, Grossi C, Borghi MO, Pierangeli SS, Meroni PL (2009) Mechanisms of action of antiphospholipid antibodies. Handbook of systemic autoimmune diseases. Antiphospholipid Syndr Syst Autoimmun Dis 10:55–67
153.
Romay-Penabad Z, Aguilar-Valenzuela R, Urbanus RT, Derksen H et al (2010) Apolipoprotein E receptor 2′ is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood. (in press)
154.
Krone KA, Allen KL, McCrae KR (2010) Impaired fibrinolysis in the antiphospholipid syndrome. Curr Rheumatol Rep 12(1):53–57PubMedPubMedCentral
155.
Griffin JH, Fernandez JA, Gale AJ, Mosnier LO (2007) Activated protein C. J Thromb Haemost 5(Suppl 1):73–80PubMed
156.
Urbanus RT, de Laat B (2010) Antiphospholipid antibodies and the protein C pathway. Lupus 19(4):394–399PubMed
157.
Atsumi T, Ieko M, Bertolaccini ML et al (2000) Association of autoantibodies against the phosphatidylserine-prothrombin complex with manifestations of the antiphospholipid syndrome and with the presence of lupus anticoagulant. Arthritis Rheum 43(9):1982–1993PubMed
158.
High KA (1988) Antithrombin III, protein C, and protein S. Naturally occurring anticoagulant proteins. Arch Pathol Lab Med 112(1):28–36PubMed
159.
Kolev K, Léránt I, Skopál J et al (2005) Impaired inactivation by antithrombin and hirudin and preserved fibrinogen-clotting activity of thrombin in complex with anti-thrombin antibody from a patient with antiphospholipid syndrome. Thromb Haemost 94(1):82–87PubMed
160.
Chamley LW, McKay EJ, Pattison NS (1993) Inhibition of heparin/antithrombin III cofactor activity by anticardiolipin antibodies: a mechanism for thrombosis. Thromb Res 71(2):103–111PubMed
161.
Shibata S, Harpel PC, Gharavi A, Rand J, Fillit H (1994) Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes. Blood 83(9):2532–2540PubMed
162.
Krikun G, Lockwood CJ, Wu XX et al (1994) The expression of the placental anticoagulant protein, annexin V, by villous trophoblasts: immunolocalization and in vitro regulation. Placenta 15(6):601–612PubMed
163.
Cugno M, Cabibbe M, Galli M et al (2004) Antibodies to tissue-type plasminogen activator (tPA) in patients with antiphospholipid syndrome: evidence of interaction between the antibodies and the catalytic domain of tPA in 2 patients. Blood 103(6):2121–2126PubMed
164.
Ames PR, Tommasino C, Iannaccone L et al (1996) Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies—a crucial role for acquired free protein S deficiency. Thromb Haemost 76(2):190–194PubMed
165.
Atsumi T, Khamashta MA, Andujar C et al (1998) Elevated plasma lipoprotein(a) level and its association with impaired fibrinolysis in patients with antiphospholipid syndrome. J Rheumatol 25(1):69–73PubMed
166.
Yang CD, Hwang KK, Yan W, Gallagher K et al (2004) Identification of anti-plasmin antibodies in the antiphospholipid syndrome that inhibit degradation of fibrin. J Immunol 172(9):5765–5773PubMed
167.
Cesarman GM, Guevara CA, Hajjar KA (1994) An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 269(33):21198–21203PubMed
168.
Ao W, Zheng H, Chen XW et al (2010) Anti-annexin II antibody is associated with thrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis. Rheumatol Int (in press)
169.
Takeuchi R, Atsumi T, Ieko M et al (2002) Suppressed intrinsic fibrinolytic activity by monoclonal anti-beta-2 glycoprotein I autoantibodies: possible mechanism for thrombosis in patients with antiphospholipid syndrome. Br J Haematol 119(3):781–788PubMed
170.
Ieko M, Ichikawa K, Atsumi T et al (2000) Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis. Semin Thromb Hemost 26(1):85–90PubMed
171.
López-Lira F, Rosales-León L, Martínez VM, Ruiz Ordaz BH (2006) The role of beta2-glycoprotein I (beta2GPI) in the activation of plasminogen. Biochim Biophys Acta 1764(4):815–823PubMed
172.
Bu C, Gao L, Xie W et al (2009) beta2-glycoprotein i is a cofactor for tissue plasminogen activator-mediated plasminogen activation. Arthritis Rheum 60(2):559–568PubMedPubMedCentral
173.
De Wolf F, Carreras LO, Moerman P et al (1982) Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. Am J Obstet Gynecol 142(7):829–834PubMed
174.
Hanly JG, Gladman DD, Rose TH et al (1988) Lupus pregnancy. A prospective study of placental changes. Arthritis Rheum 31(3):358–366PubMed
175.
Nayar R, Lage JM (1996) Placental changes in a first trimester missed abortion in maternal systemic lupus erythematosus with antiphospholipid syndrome; a case report and review of the literature. Hum Pathol 27(2):201–206PubMed
176.
Peaceman AM, Rehnberg KA (1993) The effect of immunoglobulin G fractions from patients with lupus anticoagulant on placental prostacyclin and thromboxane production. Am J Obstet Gynecol 169(6):1403–1406PubMed
177.
Rand JH, Wu XX, Guller S et al (1994) Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion. Am J Obstet Gynecol 171(6):1566–1572PubMed
178.
Rand JH, Wu XX, Guller S et al (1997) Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obstet Gynecol 177(4):918–923PubMed
179.
Wang X, Campos B, Kaetzel MA, Dedman JR (1999) Annexin V is critical in the maintenance of murine placental integrity. Am J Obstet Gynecol 180(4):1008–1016PubMed
180.
Nojima J, Kuratsune H, Suehisa E et al (2001) Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications. Clin Chem 47(6):1008–1015PubMed
181.
Donohoe S, Kingdom JC, Mackie IJ et al (2000) Ontogeny of beta 2 glycoprotein I and annexin V in villous placenta of normal and antiphospholipid syndrome pregnancies. Thromb Haemost 84(1):32–38PubMed
182.
Out HJ, Kooijman CD, Bruinse HW, Derksen RH (1991) Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies. Eur J Obstet Gynecol Reprod Biol 41(3):179–186PubMed
183.
Di Simone N, Luigi MP, Marco D et al (2007) Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature. Ann N Y Acad Sci 1108:505–514PubMed
184.
Sebire NJ, Fox H, Backos M et al (2002) Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum Reprod 17(4):1067–1071PubMed
185.
McIntyre JA (1992) Immune recognition at the maternal-fetal interface: overview. Am J Reprod Immunol 28(3–4):127–131PubMed
186.
Castellucci M, De Matteis R, Meisser A et al (2000) Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod 6(10):951–958PubMed
187.
Di Simone N, Meroni PL, de Papa N et al (2000) Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I. Arthritis Rheum 43(1):140–150PubMedPubMedCentral
188.
Katsuragawa H, Kanzaki H, Inoue T et al (1997) Monoclonal antibody against phosphatidylserine inhibits in vitro human trophoblastic hormone production and invasion. Biol Reprod 56(1):50–58PubMed
189.
Adler RR, Ng AK, Rote NS (1995) Monoclonal antiphosphatidylserine antibody inhibits intercellular fusion of the choriocarcinoma line, JAR. Biol Reprod 53(4):905–910PubMed
190.
Rote NS, Vogt E, DeVere G et al (1998) The role of placental trophoblast in the pathophysiology of the antiphospholipid antibody syndrome. Am J Reprod Immunol 39(2):125–136PubMed
191.
Chamley LW, Duncalf AM, Mitchell MD, Johnson PM (1998) Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Lancet 352(9133):1037–1038PubMed
192.
Di Simone N, Castellani R, Caliandro D, Caruso A (2002) Antiphospholipid antibodies regulate the expression of trophoblast cell adhesion molecules. Fertil Steril 77(4):805–811PubMed
193.
Di Simone N, Marana R, Castellani R et al (2010) Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation. Arthritis Rheum 62(5):1504–1512PubMed
194.
Ornoy A, Yacobi S, Matalon ST et al (2003) The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture. Lupus 12(7):573–578PubMed
195.
Matalon ST, Shoenfeld Y, Blank M et al (2004) Antiphosphatidylserine antibodies affect rat yolk sacs in culture: a mechanism for fetal loss in antiphospholipid syndrome. Am J Reprod Immunol 51(2):144–151PubMed
196.
Di Simone N, Castellani R, Raschi E et al (2006) Anti-beta-2 glycoprotein I antibodies affect Bcl-2 and Bax trophoblast expression without evidence of apoptosis. Ann N Y Acad Sci 1069:364–376PubMed
197.
Borghi MO, Raschi E, Scurati S et al (2007) Effects of a toll-like receptor antagonist and anti-annexin A2 antibodies on binding and activation of decidual cells by anti-β2glycoprotein I antibodies. Clin Exp Rheumatol 2:35
198.
Francis J, Rai R, Sebire NJ et al (2006) Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome. Mol Hum Reprod 12(7):435–442PubMed
199.
Di Simone N, Di Nicuolo F, D’Ippolito S et al (2010) Antiphospholipid antibodies affect human endometrial angiogenesis. Biol Reprod 83(2):212–219PubMed
200.
Riley JK, Nelson DM (2009) Toll-like Receptors in Pregnancy Disorders and Placental Dysfunction. Clin Rev Allergy Immunol (in press)
201.
Bogic LV, Ohira RH, Yamamoto SY et al (1999) Tissue plasminogen activator and its receptor in the human amnion, chorion, and decidua at preterm and term. Biol Reprod 60(4):1006–1012PubMed
202.
Mulla MJ, Brosens JJ, Chamley LW et al (2009) Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol 62(2):96–111PubMedPubMedCentral
203.
Mulla MJ, Myrtolli K, Brosens JJ et al (2010) Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 63(5):339–348PubMed
204.
Amigo MC (2006) Kidney disease in antiphospholipid syndrome. Rheum Dis Clin North Am 32(3):509–522PubMed
205.
Mayer M, Cerovec M, Rados M, Cikes N (2010) Antiphospholipid syndrome and central nervous system. Clin Neurol Neurosurg 112(7):602–608PubMed
206.
Tektonidou MG, Varsou N, Kotoulas G et al (2006) Cognitive deficits in patients with antiphospholipid syndrome: association with clinical, laboratory, and brain magnetic resonance imaging findings. Arch Intern Med 166(20):2278–2284PubMed
207.
Chapman J, Cohen-Armon M, Shoenfeld Y, Korczyn AD (1999) Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. Lupus 8(2):127–133PubMed
208.
Gertner E (1999) Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment. J Rheumatol 26(4):805–807PubMed
209.
Deane KD, West SG (2005) Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum 35(3):154–165PubMed
210.
Asherson RA, Cervera R, Wells AU (2005) Diffuse alveolar hemorrhage: a nonthrombotic antiphospholipid lung syndrome? Semin Arthritis Rheum 35(3):138–142PubMed
211.
Matsuura E, Kobayashi K, Hurley BL, Lopez LR (2006) Atherogenic oxidized low-density lipoprotein/beta2-glycoprotein I (oxLDL/beta2GPI) complexes in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 15(7):478–483PubMed
212.
Kobayashi K, Lopez LR, Matsuura E (2007) Atherogenic antiphospholipid antibodies in antiphospholipid syndrome. Ann N Y Acad Sci 1108:489–496PubMed
213.
Chaouat G (2007) The Th1/Th2 paradigm: still important in pregnancy? Semin Immunopathol 29(2):95–113PubMed
214.
Holers VM, Girardi G, Mo L et al (2002) Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 195(2):211–220PubMedPubMedCentral
215.
Martinez de la Torre Y, Buracchi C, Borroni EM et al (2007) Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6. Proc Natl Acad Sci USA 104(7):2319–2324PubMedPubMedCentral
216.
Quigg RJ, Kozono Y, Berthiaume D et al (1998) Blockade of antibody-induced glomerulonephritis with Crry-Ig, a soluble murine complement inhibitor. J Immunol 160(9):4553–4560PubMed
217.
Girardi G, Berman J, Redecha P et al (2003) Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 112(11):1644–1654PubMedPubMedCentral
218.
Redecha P, Tilley R, Tencati M et al (2007) Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 110(7):2423–2431PubMedPubMedCentral
219.
Girardi G, Yarilin D, Thurman JM et al (2006) Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 203(9):2165–2175PubMedPubMedCentral
220.
Girardi G, Redecha P, Salmon JE (2004) Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med 10(11):1222–1226PubMed
221.
Shamonki JM, Salmon JE, Hyjek E, Baergen RN (2007) Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol196(2):167.e1–5
222.
Cavazzana I, Manuela N, Irene C et al (2007) Complement activation in anti-phospholipid syndrome: a clue for an inflammatory process? J Autoimmun 28(2–3):160–164PubMed
223.
Stone S, Pijnenborg R, Vercruysse L et al (2006) The placental bed in pregnancies complicated by primary antiphospholipid syndrome. Placenta 27(4–5):457–467PubMed
224.
Salmon JE, Girardi G, Theodore E (2007) Woodward Award: antiphospholipid syndrome revisited: a disorder initiated by inflammation. Trans Am Clin Climatol Assoc 118:99–114PubMedPubMedCentral
225.
Pierangeli SS, Girardi G, Vega-Ostertag M et al (2005) Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum 52(7):2120–2124PubMed
226.
Romay-Penabad Z, Liu XX, Montiel-Manzano G, Papalardo De Martínez E, Pierangeli SS (2007) C5a receptor-deficient mice are protected from thrombophilia and endothelial cell activation induced by some antiphospholipid antibodies. Ann N Y Acad Sci 1108:554–566PubMed
227.
Carrera-Marin AL, Romay-Penabad Z, Qu HC et al (2009) A C5a receptor antagonist ameliorates in vivo effects of antiphospholipid antibodies. Arthritis Rheum 60:s767 (abstract)
228.
Carrera-Marin AL, Aguilar-Valenzuela R, Romay-Penabad Z et al (2010) Involvement of C6 and the MAC on in vivo antiphospholipid-mediated pathogenic effects. Lupus 19:507 (abstract)
229.
Oku K, Atsumi T, Bohgaki M et al (2009) Complement activation in patients with primary antiphospholipid syndrome. Ann Rheum Dis 68(6):1030–1035PubMed
230.
Pierangeli SS, Vega-Ostertag ME, González EB (2007) New targeted therapies for treatment of thrombosis in antiphospholipid syndrome. Expert Rev Mol Med 9(30):1–15PubMed
Metadaten
Titel
Pathophysiology of the antiphospholipid antibody syndrome
verfasst von
Rohan Willis
Silvia S. Pierangeli
Publikationsdatum
01.11.2011
Verlag
Springer International Publishing
Erschienen in
Autoimmunity Highlights / Ausgabe 2/2011
Print ISSN: 2038-0305
Elektronische ISSN: 2038-3274
DOI
https://doi.org/10.1007/s13317-011-0017-9

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