Antiphospholipid antibodies and the placenta: A systematic review of their In vitro effects and modulation by treatment

Human Reproduction Update

Volumn 21, Issue 1, 2015, Pages 97-118

  Tong, M ^a   Viall, C A ^a   Chamley, L W ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

Antiphospholipid antibody; Antiphospholipid antibody syndrome; Placenta; Pregnancy; Trophoblast

Indexed keywords

ACETYLSALICYLIC ACID; BETAMETHASONE; CHORIONIC GONADOTROPIN; COMPLEMENT; CYTOKINE; HEPARIN; HIRUDIN; HORMONE; HYDROXYCHLOROQUINE; IMMUNOGLOBULIN; INDOMETACIN; LOW MOLECULAR WEIGHT HEPARIN; PHOSPHOLIPID ANTIBODY; PLACENTAL GROWTH FACTOR; PRAVASTATIN; RECOMBINANT INTERLEUKIN 3; STEROID HORMONE; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 1;

ANTIPHOSPHOLIPID SYNDROME; APOPTOSIS; ARTICLE; BLOOD CLOTTING; CELL DEATH; CELL FUNCTION; CELL INVASION; CELL PROLIFERATION; CELL VIABILITY; COMPLEMENT ACTIVATION; CYTOKINE PRODUCTION; DATA EXTRACTION; DRUG EFFICACY; EMBASE; HORMONE SYNTHESIS; HUMAN; IN VIVO STUDY; MEDICAL RECORD REVIEW; MEDLINE; NONHUMAN; PLACENTA; PRIORITY JOURNAL; PROTEIN SECRETION; SCOPUS; SIGNAL TRANSDUCTION; SYNCYTIOTROPHOBLAST; SYSTEMATIC REVIEW; TROPHOBLAST; WEB OF SCIENCE; CELL CULTURE; CYTOLOGY; FEMALE; IMMUNOLOGY; IN VITRO STUDY; PHYSIOLOGY; PREGNANCY;

ANTIBODIES, ANTIPHOSPHOLIPID; ANTIPHOSPHOLIPID SYNDROME; BLOOD COAGULATION; CELLS, CULTURED; COMPLEMENT ACTIVATION; FEMALE; HUMANS; IN VITRO TECHNIQUES; PLACENTA; PREGNANCY; TROPHOBLASTS;

EID: 84922459743     PISSN: 13554786     EISSN: 14602369     Source Type: Journal    
DOI: 10.1093/humupd/dmu049     Document Type: Article

References (151)

1. Abir R, Ornoy A, Ben Hur H, Jaffe P, Pinus H. IgG exchange as a means of partial correction of anomalies in rat embryos in vitro, induced by sera from women with recurrent abortion. Toxicol In Vitro 1993;7:817-826.
2. Adler RR, Ng AK, Rote NS. Monoclonal antiphosphatidylserine antibody inhibits intercellular fusion of the choriocarcinoma line, JAR. Biol Reprod 1995;53:905-910.
3. Aggarwal N, Sawhney H, Vasishta K, Chopra S, Bambery P. Pregnancy in patients with systemic lupus erythematosus. Aust N Z J Obstet Gynaecol 1999;39:28-30.
4. al-Lamki RS, Skepper JN, Burton GJ. Are human placental bed giant cells merely aggregates of small mononuclear trophoblast cells? An ultrastructural and immunocytochemical study. Hum Reprod 1999;14:496-504.
5. Albert CR, Schlesinger WJ, Viall CA, Mulla MJ, Brosens JJ, Chamley LW, Abrahams VM. Effect of hydroxychloroquine on antiphospholipid antibody-induced changes in first trimester trophoblast function. Am J Reprod Immunol 2013. doi:10.1111/aji.12184.
6. Black S, Kadyrov M, Kaufmann P, Ugele B, Emans N, Huppertz B. Syncytial fusion of human trophoblast depends on caspase 8. Cell Death Differ 2004;11:90-98.
7. Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies. Proc Natl Acad Sci USA 1991;88:3069-3073.
8. Blank M, Tincani A, Shoenfeld Y. Induction of experimental antiphospholipid syndrome in naive mice with purified IgG antiphosphatidylserine antibodies. J Rheumatol 1994;21:100-104.
9. Blank M, Anafi L, Zandman-Goddard G, Krause I, Goldman S, Shalev E, Cervera R, Font J, Fridkin M, Thiesen HJ et al. The efficacy of specific IVIG anti-idiotypic antibodies in antiphospholipid syndrome (APS): trophoblast invasiveness and APS animal model. Int Immunol 2007;19:857-865.
10. Bose P, Black S, Kadyrov M, Bartz C, Shlebak A, Regan L, Huppertz B. Adverse effects of lupus anticoagulant positive blood sera on placental viability can be prevented by heparin in vitro. Am J Obstet Gynecol 2004;191:2125-2131.
11. Bose P, Kadyrov M, Goldin R, Hahn S, Backos M, Regan L, Huppertz B. Aberrations of early trophoblast differentiation predispose to pregnancy failure: lessons from the anti-phospholipid syndrome. Placenta 2006;27:869-875.
12. Branch DW, Khamashta MA. Antiphospholipid syndrome: obstetric diagnosis, management, and controversies. Obstet Gynecol 2003;101:1333-1344.
13. Branch DW, Andres R, Digre KB, Rote NS, Scott JR. The association of antiphospholipid antibodies with severe preeclampsia. Obstet Gynecol 1989;73:541-545.
14. Branch DW, Dudley DJ, Mitchell MD, Creighton KA, Abbott TM, Hammond EH, Daynes RA. 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 1990;163(Pt 1):210-216.
15. Brandt KJ, Kruithof EK, de Moerloose P. Receptors involved in cell activation by antiphospholipid antibodies. Thromb Res 2013. doi:S0049-3848(13)00370-8[pii]10.1016/j.thromres.2013.08.015.
16. Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 1967;93:569-579.
17. Bulla R, de Guarrini F, Pausa M, Fischetti F, Meroni PL, De Seta F, Guaschino S, Tedesco F. Inhibition of trophoblast adhesion to endothelial cells by the sera of women with recurrent spontaneous abortions. Am J Reprod Immunol 1999;42:116-123.
18. Burton GJ, Jauniaux E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol 2011;25:287-299.
19. Carroll TY, Mulla MJ, Han CS, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Sfakianaki AK, Paidas MJ et al. Modulation of trophoblast angiogenic factor secretion by antiphospholipid antibodies is not reversed by heparin. American Journal of Reproductive Immunology 2011;66:286-296.
20. Cartwright JE, Fraser R, Leslie K, Wallace AE, James JL. Remodelling at the maternal - fetal interface: relevance to human pregnancy disorders. Reproduction 2010;140:803-813.
21. Chamley LW. Antiphospholipid antibodies: biological basis and prospects for treatment. J Reprod Immunol 2002;57:185-202.
22. Chamley LW, Pattison NS, McKay EJ. Elution of anticardiolipin antibodies and their cofactor beta 2-glycoprotein 1 from the placentae of patients with a poor obstetric history. J Reprod Immunol 1993;25:209-220.
23. Chamley LW, Allen JL, Johnson PM. Synthesis of beta2 glycoprotein 1 by the human placenta. Placenta 1997;18:403-410.
24. Chamley LW, Duncalf AM, Mitchell MD, Johnson PM. Action of anticardiolipin and antibodies to [beta]2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Lancet 1998;352:1037-1038.
25. Chamley LW, Duncalf AM, Konarkowska B, Mitchell MD, Johnson PM. Conformationally altered beta 2-glycoprotein I is the antigen for anti-cardiolipin autoantibodies. Clin Exp Immunol 1999;115:571-576.
26. Chamley LW, Konarkowska B, Duncalf AM, Mitchell MD, Johnson PM. Is interleukin-3 important in antiphospholipid antibody-mediated pregnancy failure? Fertil Steril 2001;76:700-706.
27. Chen Q, Viall C, Kang Y, Liu B, Stone P, Chamley L. Anti-phospholipid antibodies increase non-apoptotic trophoblast shedding: a contribution to the pathogenesis of pre-eclampsia in affected women? Placenta 2009;30:767-773.
28. Chukwuocha RU, Zhu M, Cho CS, Visvanathan S, Hwang KK, Rahman A, Chen PP. Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies. Mol Immunol 2002;39:299-311.
29. Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 2006;54:3640-3647.
30. Damsky CH, Librach C, Lim KH, Fitzgerald ML, McMaster MT, Janatpour M, Zhou Y, Logan SK, Fisher SJ. Integrin switching regulates normal trophoblast invasion. Development 1994;120:3657-3666.
31. de Castellarnau C, Pich I, Borrell M, Fontcuberta J, Cabero L, Esteban-Altirriba J. Serial measurements of a plasma prostacyclin inhibitor in a patient with recurrent abortions and lupus anticoagulant; a case report. Eur J Obstet Gynecol Reprod Biol 1988;29:173-178.
32. De Wolf F, Carreras LO, Moerman P, Vermylen J, Van Assche A, Renaer M. Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. Am J Obstet Gynecol 1982;142:829-834.
33. Di Simone N, De Carolis S, Lanzone A, Ronsisvalle E, Giannice R, Caruso GA. In vitro effect of antiphospholipid antibody-containing sera on basal and gonadotrophin releasing hormone-dependent human chorionic gonadotrophin release by cultured trophoblast cells. Placenta 1995;16:75-83.
34. Di Simone N, Ferrazzani S, Castellani R, De Carolis S, Mancuso S, Caruso A. Heparin and low-dose aspirin restore placental human chorionic gonadotrophin secretion abolished by antiphospholipid antibody-containing sera. Hum Reprod 1997;12:2061-2065.
35. Di Simone N, Caliandro D, Castellani R, Ferrazzani S, De Carolis S, Caruso A. Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome. Hum Reprod 1999;14:489-495.
36. Di Simone N, Caliandro D, Castellani R, Ferrazzani S, Caruso A. Interleukin-3 and human trophoblast: in vitro explanations for the effect of interleukin in patients with antiphospholipid antibody syndrome. Fertil Steril 2000a;73:1194-1200.
37. Di Simone N, Meroni PL, Del Papa N, Raschi E, Caliandro D, De Carolis S, Khamashta MA, Atsumi T, Hughes GRV, Balestrieri G et al. Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered β 2-glycoprotein I. Arthritis Rheum 2000b;43:140-150.
38. Di Simone N, Castellani R, Caliandro D, Caruso A. Monoclonal anti-annexin V antibody inhibits trophoblast gonadotropin secretion and induces syncytiotrophoblast apoptosis. Biol Reprod 2001;65:1766-1770.
39. Di Simone N, Castellani R, Caliandro D, Caruso A. Antiphospholid antibodies regulate the expression of trophoblast cell adhesion molecules. Fertil Steril 2002;77:805-811.
40. Di Simone N, Raschi E, Testoni C, Castellani R, D'Asta M, Shi T, Krilis SA, Caruso A, Meroni PL. Pathogenic role of anti-β2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of β2-glycoprotein I binding to trophoblast cells and functional effects of anti-β2-glycoprotein I antibodies in vitro. Ann Rheum Dis 2005;64:462-467.
41. Di Simone N, Castellani R, Raschi E, Borghi MO, Meroni PL, Caruso A. Anti-beta-2 glycoprotein I antibodies affect Bcl-2 and Bax trophoblast expression without evidence of apoptosis. Ann N Y Acad Sci 2006;1069:364-376.
42. Di Simone N, Di Nicuolo F, D'Ippolito S, Castellani R, Tersigni C, Caruso A, Meroni P, Marana R. Antiphospholipid antibodies affect human endometrial angiogenesis. Biol Reprod 2010a;83:212-219.
43. Di Simone N, Marana R, Castellani R, Di Nicuolo F, D'Alessio MC, Raschi E, Borghi MO, Chen PP, Sanguinetti M, Caruso A et al. Decreased expression of heparin-binding epidermal growth factor-like growth factor as a newly identified pathogenic mechanism of antiphospholipid-mediated defective placentation. Arthritis Rheum 2010b;62:1504-1512.
44. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005;33:565.
45. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review. BMJ 2001;32:329-333.
46. Edwards MH, Pierangeli S, Liu X, Barker JH, Anderson G, Harris EN. Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 1997;96:4380-4384.
47. Empson M, Lassere M, Craig JC, Scott JR. Recurrent pregnancy loss with antiphospholipid antibody: a systematic review of therapeutic trials. Obstet Gynecol 2002;99:135-144.
48. Espinola RG, Pierangeli SS, Gharavi AE, Harris EN. Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 2002;87:518-522.
49. Faden D, Tincani A, Tanzi P, Spatola L, Lojacono A, Tarantini M, Balestrieri G. Anti-beta 2 glycoprotein I antibodies in a general obstetric population: preliminary results on the prevalence and correlation with pregnancy outcome. Anti-beta2 glycoprotein I antibodies are associated with some obstetrical complications, mainly preeclampsia - eclampsia. Eur J Obstet Gynecol Reprod Biol 1997;73:37-42.
50. Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 2002;100:408-413.
51. Finucane DM, Bossy-Wetzel E, Waterhouse NJ, Cotter TG, Green DR. Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J Biol Chem 1999;274:2225-2233.
52. Fisher SJ, Cui TY, Zhang L, Hartman L, Grahl K, Zhang GY, Tarpey J, Damsky CH. Adhesive and degradative properties of human placental cytotrophoblast cells in vitro. J Cell Biol 1989;109:891-902.
53. Frank GR, Brar AK, Cedars MI, Handwerger S. Prostaglandin E2 enhances human endometrial stromal cell differentiation. Endocrinology 1994;134:258-263.
54. Franklin RD, Kutteh WH. Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro. Obstet Gynecol 2003;101: 455-462.
55. Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van Breda-Vriesman PJ, Barbui T, Zwaal RF, Bevers EM. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;33:1544-1547.
56. Gardlund B. The lupus inhibitor in thromboembolic disease and intrauterine death in the absence of systemic lupus. Acta Med Scand 1984;215:293-298.
57. Giles IP, Isenberg DA, Latchman DS, Rahman A. How do antiphospholipid antibodies bind beta2-glycoprotein I? Arthritis Rheum 2003;48:2111-2121.
58. Girardi G. Pravastatin prevents miscarriages in antiphospholipid antibody-treated mice. J Reprod Immunol 2009;82:126-131.
59. Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 2003;112:1644-1654.
60. Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med 2004;10:1222-1226.
61. Gleicher N, Harlow L, Zilberstein M. Regulatory effect of antiphospholipid antibodies on signal transduction: a possible model for autoantibody-induced reproductive failure. Am J Obstet Gynecol 1992;167:637-642.
62. Graham CH, Lala PK. Mechanisms of placental invasion of the uterus and their control. Biochem Cell Biol 1992;70:867-874.
63. 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;277:2644-2649.
64. Han CS, Mulla MJ, Brosens JJ, Chamley LW, Paidas MJ, Lockwood CJ, Abrahams VM. Aspirin and heparin effect on basal and antiphospholipid antibody modulation of trophoblast function. Obstet Gynecol 2011;118:1021-1028.
65. Hasegawa I, Takakuwa K, Adachi S, Kanazawa K. Cytotoxic antibody against trophoblast and lymphocytes present in pregnancy with intra-uterine fetal growth retardation and its relation to anti-phospholipid antibody. J Reprod Immunol 1990;17:127-139.
66. Holers VM, Girardi G, Mo L, Guthridge JM, Molina H, Pierangeli SS, Espinola R, Xiaowei LE, Mao D, Vialpando CG et al. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 2002;195:211-220.
67. Ichikawa G, Yamamoto T, Chishima F, Nakamura A, Kuno S, Murase T, Suzuki M. Effects of anti-beta2-glycoprotein I antibody on PlGF, VEGF and sVEGFR1 production from cultured choriocarcinoma cell line. J Obstet Gynaecol Res 2011;37:1076-1083.
68. Ikematsu W, Luan FL, La Rosa L, Beltrami B, Nicoletti F, Buyon JP, Meroni PL, Balestrieri G, Casali P. Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice. Arthritis Rheum 1998;41:1026-1039.
69. Iwasawa Y, Kawana K, Fujii T, Schust DJ, Nagamatsu T, Kawana Y, Sayama S, Miura S, Matsumoto J, Adachi K et al. A possible coagulation-independent mechanism for pregnancy loss involving beta(2) glycoprotein 1-dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012;67:54-65.
70. Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril 2010;93:1234-1243.
71. Jiang X, Wang X. Cytochrome C-mediated apoptosis. Annu Rev Biochem 2004;73:87-106.
72. Jovanovic M, Bozic M, Kovacevic T, Radojcic L, Petronijevic M, Vicovac L. Effects of anti-phospholipid antibodies on a human trophoblast cell line (HTR-8/SVneo). Acta Histochem 2010;112:34-41.
73. Kam EP, Gardner L, Loke YW, King A. The role of trophoblast in the physiological change in decidual spiral arteries. Hum Reprod 1999;14:2131-2138.
74. Katsuragawa H, Kanzaki H, Inoue T, Hirano T, Mori T, Rote NS. Monoclonal antibody against phosphatidylserine inhibits in vitro human trophoblastic hormone production and invasion. Biol Reprod 1997;56:50-58.
75. Kovacevic TM, Radojcic L, Tosic NM, Pavlovic ST, Vicovac LM. Monoclonal antibody 26 cross-reactive with beta2-glycoprotein I affects human trophoblast invasion in vitro. Eur J Obstet Gynecol Reprod Biol 2013;171:23-29.
76. La Rosa L, Meroni PL, Tincani A, Balestrieri G, Faden D, Lojacono A, Morassi L, Brocchi E, Del Papa N, Gharavi A et al. Beta 2 glycoprotein I and placental anticoagulant protein I in placentae from patients with antiphospholipid syndrome. J Rheumatol 1994;21:1684-1693.
77. Lau IF, Saksena SK, Chang MC. Pregnancy blockade by indomethacin, an inhibitor of prostaglandin synthesis: its reversal by prostaglandins and progesterone in mice. Prostaglandins 1973;4:795-803.
78. Levine JS, Subang R, Koh JS, Rauch J. Induction of anti-phospholipid autoantibodies by beta2-glycoprotein I bound to apoptotic thymocytes. J Autoimmun 1998;11:413-424.
79. Levy RA, Vilela VS, Cataldo MJ, Ramos RC, Duarte JL, Tura BR, Albuquerque EM, Jesus NR. Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 2001;10:401-404.
80. Lockshin MD, Druzin ML, Goei S, Qamar T, Magid MS, Jovanovic L, Ferenc M. Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N Engl J Med 1985;313:152-156.
81. Lockwood CJ, Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins JC. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. Am J Obstet Gynecol 1989;161:369-373.
82. Lyden TW, Ng AK, Rote NS. Modulation of phosphatidylserine epitope expression by BeWo cells during forskolin treatment. Placenta 1993;14:177-186.
83. Lynch A, Marlar R, Murphy J, Davila G, Santos M, Rutledge J, Emlen W. Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study. Ann Intern Med 1994;120:470-475.
84. MacLean MA, Cumming GP, McCall F, Walker ID, Walker JJ. The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages. Br J Obstet Gynaecol 1994;101:103-106.
85. Magid MS, Kaplan C, Sammaritano LR, Peterson M, Druzin ML, Lockshin MD. Placental pathology in systemic lupus erythematosus: a prospective study. Am J Obstet Gynecol 1998;179:226-234.
86. Mak IY, Brosens JJ, Christian M, Hills FA, Chamley L, Regan L, White JO. Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro. J Clin Endocrinol Metab 2002;87:2581-2588.
87. Marchetti T, Ruffatti A, Wuillemin C, de Moerloose P, Cohen M. Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies. J Thromb Haemost 2014. doi:10.1111/jth.12570.
88. McIntyre JA, Wagenknecht DR, Sugi T. Phospholipid binding plasma proteins required for antiphospholipid antibody detection-an overview. Am J Reprod Immunol 1997;37:101-110.
89. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, PG DEG, Koike T, Meroni PL et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306.
90. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6:e1000097.
91. Mulla MJ, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Joyce SK, Panda B, Paidas MJ, Abrahams VM. Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol 2009;62:96-111.
92. Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010;63:339-348.
93. Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB, Abrahams VM. A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1beta production by human first trimester trophoblast. PLoS One 2013;8:e65237.
94. Nilkaeo A, Bhuvanath S. Interleukin-1 modulation of human placental trophoblast proliferation. Mediators Inflamm 2006;2006:79359.
95. Odiari EA, Mulla MJ, Sfakianaki AK, Paidas MJ, Stanwood NL, Gariepy A, Brosens JJ, Chamley LW, Abrahams VM. Pravastatin does not prevent antiphospholipid antibody-mediated changes in human first trimester trophoblast function. Hum Reprod 2012. doi:10.1093/humrep/des288.
96. Oksenberg JR, Brautbar C. In vitro suppression of murine blastocysts growth by sera from women with reproductive disorders. Am J Reprod Immunol Microbiol 1986;11:118-124.
97. Oliveira SH, Canetti C, Ribeiro RA, Cunha FQ. Neutrophil migration induced by IL-1beta depends upon LTB4 released by macrophages and upon TNF-alpha and IL-1beta released by mast cells. Inflammation 2008;31:36-46.
98. Orendi K, Gauster M, Moser G, Meiri H, Huppertz B. The choriocarcinoma cell line BeWo: syncytial fusion and expression of syncytium-specific proteins. Reproduction 2010;140:759-766.
99. Ornoy A, Yacobi S, Avraham S, Blumenfeld Z. The effect of sera from women with systemic lupus erythematosus and/or antiphospholipid syndrome on rat embryos in culture. Reprod Toxicol 1998;12:185-191.
100. Ornoy A, Yacobi S, Matalon ST, Blank M, Blumenfeld Z, Miller RK, Shoenfeld Y. The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture. Lupus 2003;12:573-578.
101. Oshiro BT, Silver RM, Scott JR, Yu H, Branch DW. Antiphospholipid antibodies and fetal death. Obstet Gynecol 1996;87:489-493.
102. Ozaki K, Hanazawa S, Takeshita A, Chen Y, Watanabe A, Nishida K, Miyata Y, Kitano S. Interleukin-1 beta and tumor necrosis factor-alpha stimulate synergistically the expression of monocyte chemoattractant protein-1 in fibroblastic cells derived from human periodontal ligament. Oral Microbiol Immunol 1996;11:109-114.
103. Pantham P, Rosario R, Chen Q, Print CG, Chamley LW. Transcriptomic analysis of placenta affected by antiphospholipid antibodies: following the TRAIL of trophoblast death. J Reprod Immunol 2012;94:151-154.
104. Parke A, West B. Hydroxychloroquine in pregnant patients with systemic lupus erythematosus. J Rheumatol 1996;23:1715-1718.
105. Pattison NS, Chamley LW, McKay EJ, Liggins GC, Butler WS. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations. Br J Obstet Gynaecol 1993;100:909-913.
106. Pattison NS, Chamley LW, Birdsall M, Zanderigo AM, Liddell HS, McDougall J. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol 2000;183:1008-1012.
107. Peaceman AM, Rehnberg KA. The effect of immunoglobulin G fractions from patients with lupus anticoagulant on placental prostacyclin and thromboxane production. Am J Obstet Gynecol 1993;169:1403-1406.
108. Peaceman AM, Rehnberg KA. The effect of aspirin and indomethacin on prostacyclin and thromboxane production by placental tissue incubated with immunoglobulin G fractions from patients with lupus anticoagulant. Am J Obstet Gynecol 1995;173:1391-1396.
109. Pennings MT, van Lummel M, Derksen RH, Urbanus RT, Romijn RA, Lenting PJ, de Groot PG. Interaction of beta2-glycoprotein I with members of the low density lipoprotein receptor family. J Thromb Haemost 2006;4:1680-1690.
110. 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;52:2120-2124.
111. Pierro E, Cirino G, Bucci MR, Lazzarin N, Andreani CL, Mancuso S, Lanzone A, Navarra P. Antiphospholipid antibodies inhibit prostaglandin release by decidual cells of early pregnancy: possible involvement of extracellular secretory phospholipase A2. Fertil Steril 1999;71:342-346.
112. Prutsch N, Fock V, Haslinger P, Haider S, Fiala C, Pollheimer J, Knofler M. The role of interleukin-1beta in human trophoblast motility. Placenta 2012;33:696-703.
113. Quenby S, Mountfield S, Cartwright JE, Whitley GS, Vince G. Effects of low-molecular-weight and unfractionated heparin on trophoblast function. Obstet Gynecol 2004;104:354-361.
114. Quenby S, Mountfield S, Cartwright JE, Whitley GS, Chamley L, Vince G. Antiphospholipid antibodies prevent extravillous trophoblast differentiation. Fertil Steril 2005;83:691-698.
115. Radway-Bright EL, Inanc M, Isenberg DA. Animal models of the antiphospholipid syndrome. Rheumatology (Oxford) 1999;38:591-601.
116. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997;31:253-257.
117. Rand JH, Wu XX, Guller S, Gil J, Guha A, Scher J, Lockwood CJ. Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion. Am J Obstet Gynecol 1994;171:1566-1572.
118. Rand JH, Wu XX, Andree HAM, Lockwood CJ, Guller S, Scher J, Harpel PC. Pregnancy loss in the antiphospholipid-antibody syndrome-a possible thrombogenic mechanism. N Engl J Med 1997a;337:154-160.
119. Rand JH, Wu XX, Guller S, Scher J, Andree HAM, Lockwood CJ. Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obstet Gynecol 1997b;177:918-923.
120. Rand JH, Wu XX, Quinn AS, Chen PP, McCrae KR, Bovill EG, Taatjes DJ. Human monoclonal antiphospholipid antibodies disrupt the annexin A5 anticoagulant crystal shield on phospholipid bilayers: evidence from atomic force microscopy and functional assay. Am J Pathol 2003;163:1193-1200.
121. Rand JH, Wu XX, Lapinski R, van Heerde WL, Reutelingsperger CP, Chen PP, Ortel TL. Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome. Blood 2004;104:2783-2790.
122. Rand JH, Wu XX, Quinn AS, Ashton AW, Chen PP, Hathcock JJ, Andree HAM, Taatjes DJ. Hydroxychloroquine protects the annexinA5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug. Blood 2010;115:2292-2299.
123. Redecha P, Tilley R, Tencati M, Salmon JE, Kirchhofer D, Mackman N, Girardi G. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 2007;110:2423-2431.
124. Redecha P, van Rooijen N, Torry D, Girardi G. Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. Blood 2009;113:4101-4109.
125. Riddell MR, Winkler-Lowen B, Jiang Y, Davidge ST, Guilbert LJ. Pleiotropic actions of forskolin result in phosphatidylserine exposure in primary trophoblasts. PLoS One 2013;8:e81273.
126. Romay-Penabad Z, Aguilar-Valenzuela R, Urbanus RT, Derksen RH, Pennings MT, Papalardo E, Shilagard T, Vargas G, Hwang Y, de Groot PG et al. Apolipoprotein E receptor 2 is involved in the thrombotic complications in a murine model of the antiphospholipid syndrome. Blood 2011;117:1408-1414.
127. Rote NS, Vogt E, Devere G, Obringer AR, Ng AHK. The role of placental trophoblast in the pathophysiology of the antiphospholipid antibody syndrome. Am J Reprod Immunol 1998;39:125-136.
128. Salafia CM, Cowchock FS. Placental pathology and antiphospholipid antibodies: a descriptive study. Am J Perinatol 1997;14:435-441.
129. Salafia CM, Parke AL. Placental pathology in systemic lupus erythematosus and phospholipid antibody syndrome. Rheum Dis Clin North Am 1997;23:85-97.
130. Salmon JE, Girardi G, Holers VM. Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann Rheum Dis 2002;61(Suppl. 2):ii46-50.
131. Sankaran S, Kyle PM. Aetiology and pathogenesis of IUGR. Best Pract Res Clin Obstet Gynaecol 2009;23:765-777.
132. Satta N, Kruithof EK, Fickentscher C, Dunoyer-Geindre S, Boehlen F, Reber G, Burger D, de Moerloose P. Toll-like receptor 2 mediates the activation of human monocytes and endothelial cells by antiphospholipid antibodies. Blood 2011;117:5523-5531.
133. Schwartz N, Shoenfeld Y, Barzilai O, Cervera R, Font J, Blank M, Yacobi S, Patlas N, Cohen A, Mevorach D et al. Reduced placental growth and hCG secretion in vitro induced by antiphospholipid antibodies but not by anti-Ro or anti-La: studies on sera from women with SLE/PAPS. Lupus 2007;16:110-120.
134. Sebire NJ, Fox H, Backos M, Rai R, Paterson C, Regan L. Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum Reprod 2002;17:1067-1071.
135. Shamonki JM, Salmon JE, Hyjek E, Baergen RN. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol 2007;196:167 e161-165.
136. Sheppard BL, Bonnar J. An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation. Br J Obstet Gynaecol 1981;88:695-705.
137. Shurtz-Swirski R, Inbar O, Blank M, Cohen J, Bakimer R, Shoenfeld Y. In vitro effect of anticardiolipin autoantibodies upon total and pulsatile placental hCG secretion during early pregnancy. Am J Reprod Immunol 1993;29:206-210.
138. Sthoeger ZM, Mozes E, Tartakovsky B. Anti-cardiolipin antibodies induce pregnancy failure by impairing embryonic implantation. Proc Natl Acad Sci USA 1993;90:6464-6467.
139. Stone S, Pijnenborg R, Vercruysse L, Poston R, Khamashta MA, Hunt BJ, Poston L. The placental bed in pregnancies complicated by primary antiphospholipid syndrome. Placenta 2006;27:457-467.
140. Tincani A, Lojacono A, Taglietti M, Motta M, Biasini C, Decca L, Zatti S, Frassi M, Barbetti L, Gorla R et al. Pregnancy and neonatal outcome in primary antiphospholipid syndrome. Lupus 2002;11:649.
141. 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;25:642-648.
142. Verlohren S, Geusens N, Morton J, Verhaegen I, Hering L, Herse F, Dudenhausen JW, Muller DN, Luft FC, Cartwright JE et al. Inhibition of trophoblast-induced spiral artery remodeling reduces placental perfusion in rat pregnancy. Hypertension 2010;56:304-310.
143. Viall CA, Chen Q, Liu B, Hickey A, Snowise S, Salmon JE, Stone PR, Chamley LW. Antiphospholipid antibodies internalised by human syncytiotrophoblast cause aberrant cell death and the release of necrotic trophoblast debris. J Autoimmun 2013;47:45-57.
144. Viall CA, Holloway H, Chen Q, Stone PR, Chamley LW. Development of a simple, cost-effective, semi-correlative light and electron microscopy method to allow the immunoelectron localisation of non-uniformly distributed placental proteins. Placenta 2014;35:223-227.
145. Vogt E, Ng AK, Rote NS. Antiphosphatidylserine antibody removes annexin-V and facilitates the binding of prothrombin at the surface of a choriocarcinoma model of trophoblast differentiation. Am J Obstet Gynecol 1997;177:964-972.
146. Wice B, Menton D, Geuze H, Schwartz AL. Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 1990;186:306-316.
147. Wu XX, Guller S, Rand JH. Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression. Am J Obstet Gynecol 2011;205:576.e7-576.e14.
148. Wu ZM, Yang H, Li M, Yeh CC, Schatz F, Lockwood CJ, Di W, Huang SJ. Pro-inflammatory cytokine-stimulated first trimester decidual cells enhance macrophage-induced apoptosis of extravillous trophoblasts. Placenta 2012;33:188-194.
149. Yacobi S, Ornoy A, Blumenfeld Z, Miller RK. Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture. Teratology 2002;66:300-308.
150. Yasuda M, Takakuwa K, Tokunaga A, Tanaka K. Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet Gynecol 1995; 86(4 Pt 1):555-559.
151. Zhou Y, Fisher SJ, Janatpour M, Genbacev O, Dejana E, Wheelock M, Damsky CH. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest 1997;99: 2139-2151.