A+ A A-

Download article

Volkova M.V.*, Kunder E.V.**, Generalov I.I.*, Roggenbuck D.***
Antiphospholipid antibodies: modern concepts of the pathogenetic action and laboratory determination
*Education Establishment "Vitebsk State Order of Peoples’ Friendship Medical University", Republic of Belarus
**State Educational Establishment "Belarusian Medical Academy of Post-Graduate Education",  Republic of Belarus
***Brandenburg University of Technology, Germany

The study of antiphospholipid syndrome is a priority for modern health care. This is due to the high demographic significance of this pathology. Antiphospholipid antibodies greatly contribute to the development of obstetric pathology, such conditions as miscarriage, premature birth, and others. Also antiphospholipid antibodies significantly affect the development of fatal thrombotic events (myocardial infarction, cerebral infarction) in all age groups. Laboratory diagnosis of antiphospholipid syndrome has objective difficulties because of low sensitivity of enzyme immunoassay. Nowadays new antiphospholipid antibodies tests based on linear immunoassay method are developed. They have higher sensitivity in comparison with enzyme immunoassay. This review discusses recent data on the pathogenesis, clinical manifestations of antiphospholipid syndrome and new diagnostic approaches in the antiphospholipid antibodies determination.
Key words: antiphospholipid antibodies, antiphospholipid syndrome, enzyme immunoassay, linear immunoassay.


       1. Hughes GR. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br Med J (Clin Res Ed). 1983 Oct;287(6399):1088-9.
       2. Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramón E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, Tincani A, Taglietti M, Theodossiades G, Nomikou E, Galeazzi M, Bellisai F, Meroni PL, Derksen RH, de Groot PG, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quéré I, Hachulla E, Vasconcelos C, Fernández-Nebro A, Haro M, Amoura Z, Miyara M, Tektonidou M, Espinosa G, Bertolaccini ML, Khamashta MA. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015 Jun;74(6):1011-8.
       3. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295-306.
       4. Pangborn M. Isolation and purification of a serologically active phospholipid from beef heart. J Biol Chem. 1942;143:247-56.
       5. Nowicki M. Characterization of the Cardiolipin Synthase from Arabidopsis thaliana. Skierniewice, Polen: RWTH-Aachen University; 2006.
       6. Schlame M, Brody S, Hostetler KY. Mitochondrial cardiolipin in diverse eukaryotes. Eur J Biochem. 1993 Mar;212(3):727-35.
       7. de Laat B, Mertens K, de Groot PG. Mechanisms of disease: antiphospholipid antibodies – from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol. 2008 Apr;4(4):192-9.
       8. Caronti B, Calderaro C, Alessandri C, Conti F, Tinghino R, Palladini G, Valesini G. Beta2-glycoprotein 1 (beta2-GP1) mRNA is expressed by several cell types involved in anti-phospholipid syndrome-related tissue damage. Clin Exp Immunol. 1999 Jan;115(1):214-9.
       9. de Laat B, Derksen RHWM, Urbanus RT, de Groot PG. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2-glycoprotein I cause AC, and their presence correlates strongly with thrombosis. Blood. 2005 Feb;105(4):1540-5.
       10. de Groot PG, Urbanus RT. The significance of autoantibodies against β2-glycoprotein I / P. G. de Groot, R. T. Urbanus. Blood. 2012 Jul;120(2):266-74.
       11. Comarmond C, Cacoub P. Antiphospholipid syndrome: from pathogenesis to novel immunomodulatory therapies. Autoimmun Rev. 2013 May;12(7):752-7.
       12. van Lummel M, Pennings MT, Derksen RH, Urbanus RT, Lutters BC, Kaldenhoven N, de Groot PG. The binding site in {beta}2-glycoprotein I for ApoER2 on platelets is located is in domain V. J Biol Chem. 2005 Nov;280(44):36729-36.
       13. Triplett DA. Antiphospholipid antibodies. Arch Pathol Lab Med. 2002 Nov;126(11):1424-9.
       14. Rand JH. Antiphospholipid antibody syndrome: new insights on thrombogenic mechanisms. Am J Med Sci. 1998 Aug;316(2):142-51.
       15. Rand JH, Wu XX, Quinn AS, Chen PP, Hathcock JJ, Taatjes DJ. Hydroxychloroquine directly reduces the binding of antiphospholipid antibody- β2-glycoprotein I complexes to phospholipid bilayers. Blood. 2008 Sep;112(5):1687-95.
       16. Yoon KH. Sufficient evidence to consider hydroxychloroquine as an adjunct therapy in antiphospholipid antibody (Hughes’) syndrome. J Rheumatol. 2002 Jul;29(7):1574-5.
       17. Fishman P, Bakimer R, Blank M, Sredni D, Djaldetti M, Shoenfeld Y. The putative role of cytokines in the induction of primary anti-phospholipid syndrome in mice. Clin Exp Immunol. 1992 Nov;90(2):266-70.
       18. Karakantza M, Theodorou GL, Meimaris N, Mouzaki A, John E, Andonopoulos AP, Maniatis A. Type 1 and type 2 cytokine-producing CD4+ and CD8+ T cells in primary antiphospholipid syndrome. Ann Hematol. 2004 Nov;83(11):704-11.
       19. Salmon J, Girardi G, Holers V. Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann Rheum Dis. 2002 Nov;61(Suppl 2):ii46-ii50.
       20. Carrera-Marín A, Romay-Penabad Z, Papalardo E, Reyes-Maldonado E, García-Latorre E, Vargas G, Shilagard T, Pierangeli S. C6 knock-out mice are protected from thrombophilia mediated by antiphospholipid antibodies. Lupus. 2012 Dec;21(14):1497-505.
       21. Davis WD, Brey RL. Antiphospholipid antibodies and complement activation in patients with cerebral ischemia. Clin Exp Rheumatol. 1992 Sep-Oct;10(5):455-60.
       22. D'Ippolito S, Meroni PL, Koike T, Veglia M, Scambia G, Di Simone N. Obstetric antiphospholipid syndrome: A recent classification for an old defined disorder. Autoimmun Rev. 2014 Sep;13(9):901-8.
       23. Korabecna M, Ulcova-Gallova Z, Horinek A, Pazourková E, Calda P. Quantification of circulating fetal DNA as a tool for potential monitoring of pregnant patients with antiphospholipid antibodies. Autoimmunity. 2014 Nov;47(7):473-7.
       24. Nalli C, Iodice A, Andreoli L, Lojacono A, Motta M, Fazzi E, Tincani A. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes. Lupus. 2014 May;23(6):507-17.
       25. Kovács M, Hartwig M, Aleksza M, Tihanyi M, Nagy T, Vajda G, Daru J, Gasztonyi B. Antiphospholipid antibodies in relation to sterility/infertility. Hum Immunol. 2012 Jul;73(7):726-31.
       26. Steinvil A, Raz R, Berliner S, Steinberg DM, Zeltser D, Levran D, Shimron O, Sella T, Chodick G, Shalev V, Salomon O. Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilization. Thromb Haemost. 2012 Dec;108(6):1192-7.
       27. Kokcu A, Yavuz E, Celik H, Bildircin D. A panoramic view to relationship between reproductive failure and immunological factors. Arch Gynecol Obstet. 2012 Nov;286(5):1283-9.
       28. Proietta M, Ferrero S, Del Porto F. Prevalence of antiphospholipid antibodies in patients with sterility undergoing “in vitro” fertilization. Lupus. 2014 Jun;23(7):724-5.
       29. Motak-Pochrzest H, Malinowski A. The occurrence of immunological disturbances in patients with recurrent miscarriage (RM) of unknown etiology. Neuro Endocrinol Lett. 2013;34(7):701-7.
       30. Djokovic A, Stojanovich L, Kontic M, Stanisavljevic N, Radovanovic S, Marisavljevic D. Association between cardiac manifestations and antiphospholipid antibody type and level in a cohort of Serbian patients with primary and secondary antiphospholipid syndrome. Isr Med Assoc J. 2014 Mar;16(3):162-7.
       31. Gustafsson JT, Gunnarsson I, Källberg H, Pettersson S, Zickert A, Vikerfors A, Möller S, Rönnelid J, Elvin K, Svenungsson E. Cigarette smoking, antiphospholipid antibodies and vascular events in Systemic Lupus Erythematosus. Ann Rheum Dis. 2014 Apr.
       32. Morrisroe KB, Stevens W, Nandurkar H, Prior D, Thakkar V, Roddy J, Zochling J, Sahhar J, Tymms K, Sturgess A, Major G, Kermeen F, Hill C, Walker J, Nash P, Gabbay E, Youssef P, Proudman SM, Nikpour M. The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis. Clin Exp Rheumatol. 2014 Nov-Dec;32(6):133-7.
       33. Pezzini A, Grassi M, Lodigiani C, Patella R, Gandolfo C, Zini A, Delodovici ML, Paciaroni M, Del Sette M, Toriello A, Musolino R, Calabrò RS, Bovi P, Adami A, Silvestrelli G, Sessa M, Cavallini A, Marcheselli S, Bonifati DM, Checcarelli N, Tancredi L, Chiti A, Del Zotto E, Spalloni A, Giossi A, Volonghi I, Costa P, Giacalone G, Ferrazzi P, Poli L, Morotti A, Rasura M, Simone AM, Gamba M, Cerrato P, Micieli G, Melis M, Massucco D, De Giuli V, Iacoviello L, Padovani A. Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults. Circulation. 2014 Apr;129(16):1668-76.
       34. Ruffatti A, Del Ross T, Ciprian M, Bertero MT, Sciascia S, Scarpato S, Montecucco C, Rossi S, Caramaschi P, Biasi D, Doria A, Rampudda M, Monica N, Fischetti F, Picillo U, Brucato A, Salvan E, Vittorio P, Meroni P, Tincani A. Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study. Ann Rheum Dis. 2011 Jun;70(6):1083-6.
       35. Pengo V, Ruffatti A, Legnani C, Testa S, Fierro T, Marongiu F, De Micheli V, Gresele P, Tonello M, Ghirarduzzi A, Bison E, Denas G, Banzato A, Padayattil Jose S, Iliceto S. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011 Oct;118(17):4714-8.
       36. Cojocaru IM, Cojocaru M, Popescu AN, Popescu L, Tănăsescu R. Study of antiphospholipid antibodies in type 2 diabetes mellitus with and without diabetic retinopathy. Rom J Intern Med. 2009;47(3):267-71.
       37. Greco TP, Conti-Kelly AM, Greco T Jr, Doyle R, Matsuura E, Anthony JR, Lopez LR. Newer antiphospholipid antibodies predict adverse outcomes in patients with acute coronary syndrome. Am J Clin Pathol. 2009 Oct;132(4):613-20.
       38. Aykan AÇ, Gökdeniz T, Kalçık M, Astarcıoğlu MA, Gündüz S, Karakoyun S, Gürsoy MO, Oğuz AE, Ertürk E, Çakal B, Bayram Z, Özkan M. Role of anticardiolipin antibodies in the pathogenesis of prosthetic valve thrombosis : An observational study. Herz. 2015 May;40(3):528-533.
       39. Harris EN, Gharavi AE, Boey ML, Patel BM, Mackworth-Young CG, Loizou S, Hughes GR. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet. 1983 Nov;2(8361):1211-4.
       40. Arvieux J, Roussel B, Jacob MC, Colomb MG. Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoprotein I as an antigen. J Immunol Methods. 1991 Oct;143(2):223-9.
       41. Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med. 1994 Feb;179(2):457-62.
       42. de Laat B, de Groot PG. Autoantibodies directed against domain I of beta2-glycoprotein I. Curr Rheumatol Rep. 2011 Feb;13(1):70-6.
       43. Lakos G, Favaloro EJ, Harris EN, Meroni PL, Tincani A, Wong RC, Pierangeli SS. International consensus guidelines on anticardiolipin and anti-β2-glycoprotein I testing: report from the 13th international Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012 Jan;64(1):1-10.
       44. Egerer K, Roggenbuck D, Büttner T, Lehmann B, Kohn A, von Landenberg P, Hiemann R, Feist E, Burmester GR, Dörner T. Single-step autoantibody profiling in antiphospholipid syndrome using a multi-line dot assay. Arthritis Res Ther. 2011 Jul;13(4):R118.
       45. Chabraoui F, Derrington EA, Mallie-Didier F, Confavreux C, Quincy C, Caudie C. Dot-blot immunodetection of antibodies against GM1 and other gangliosides on PVDF-P membranes. J Immunol Methods. 1993 Oct;165(2):225-30.
       46. Forastiero RR, Martinuzzo ME, Carreras LO. Binding properties of antibodies to prothrombin and beta2-glycoprotein I (beta2-GPI) assayed by ELISA and dot blot. Clin Exp Immunol. 1999 Dec;118(3):480-6.
       47. Nash MJ, Camilleri RS, Kunka S, Mackie IJ, Machin SJ, Cohen H. The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies. J Thromb Haemost. 2004 Jul;2(7):1077-81.

Поиск по сайту