Antiphospholipid antibodies as diagnostic markers for obstetric antiphospholipid syndrome

Menzhinskaya I.V., Vanko L.V.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow
The authors have carried out a systems analysis of the data available in the current scientific literature on the spectrum and prevalence of antiphospholipid antibodies, their diagnostic and prognostic value in obstetric antiphospholipid syndrome. Detection techniques detection and the efficiency of using the antiphospholipid antibodies not included in the classification laboratory criteria for antiphospholipid syndrome in order to diagnose obstetric antiphospholipid syndrome are considered. The detection of the antiphospholipid antibody profile that includes anti-annexin A5 antibodies, the phosphatidylserine/prothrombin complex, phosphatidylethanolamine, and some negatively charged phospholipids contributes to the complete identification of patients with antiphospholipid syndrome and to the stratification of a risk for thrombosis and pregnancy complications. However, it is necessary to standardize these tests for practical use and to confirm the clinical significance of antiphospholipid antibodies in prospective studies.

Keywords

obstetric antiphospholipid syndrome
laboratory criteria for antiphospholipid syndrome
antiphospholipid antibody profile

References

  1. Cervera R., Balasch J. Autoimmunity and recurrent pregnancy losses. Clin. Rev. Allergy Immunol. 2010; 39(3): 148-52.
  2. Santos T.D.S., Ieque A.L., de Carvalho H.C., Sell A.M., Lonardoni M.V.C., Demarchi I.G. et al. Antiphospholipid syndrome and recurrent miscarriage: A systematic review and meta-analysis. J. Reprod. Immunol. 2017; 123: 78-87.
  3. D’Ippolito S., Meroni P.L., Koike T., Veglia M., Scambia G., Di Simone N. Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder. Autoimmun. Rev. 2014; 13(9): 901-8.
  4. Willis R., Pierangeli S.S. Anti-β2- glycoprotein I antibodies. Ann. N.Y. Acad. Sci. 2013; 1285: 44-58.
  5. Miyakis S., Lockshin M.D., Atsumi T., Branch D.W., Brey R.L., Cervera R. et al. J. Thromb. Haemost. 2006; 4(2): 295-306.
  6. Alijotas-Reig J., Ferrer-Oliveras R., Ruffatti A., Tincani A., Lefkou E., Bertero M.T. et al. The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 247 consecutive cases. Autoimmun. Rev. 2015; 14(5): 387-95.
  7. Galarza-Maldonado C., Kourilovitch M.R., Perez-Fernandez O.M., Gaybor M., Cordero C., Cabrera S., Soroka N.F. Obstetric antiphospholipid syndrome. Autoimmun. Rev. 2012; 11(4): 288-95.
  8. Gardiner C., Hills J., Machin S.J., Cohen H. Diagnosis of antiphospholipid syndrome in routine clinical practice. Lupus. 2013; 22(1): 18-25.
  9. Devreese K.M., Pierangeli S.S., de Laat B., Tripodi A., Atsumi T., Ortel T.L. Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH. J. Thromb. Haemost. 2014; 12(5): 792-5.
  10. Egerer K., Roggenbuck D., Büttner T., Lehmann B., Kohn A., von Landenberg P. et al. Single-step autoantibody profiling in antiphospholipid syndrome using a multi-line dot assay. Arthritis Res. Ther. 2011; 13(4): R118.
  11. De Craemer A.S., Musial .J, Devreese K.M. Role of anti-domain 1-β2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. J. Thromb. Haemost. 2016; 14(9): 1779-87.
  12. Pengo V., Tripodi A., Reber G., Rand J.H., Ortel T.L., Galli M. et al. Update of the guidelines for lupus anticoagulant detection. J. Thromb. Haemost. 2009; 7(10): 1737-40.
  13. Kwak-Kim J., Agcaoili M.S., Aleta L., Liao A., Ota K., Dambaeva S. et al. Management of women with recurrent pregnancy losses and antiphospholipid antibody syndrome. Am. J. Reprod. Immunol. 2013; 69(6): 596-607.
  14. Opatrny L., David M., Kahn S.R., Shrier I., Rey E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a meta-analysis. J. Rheumatol. 2006; 33(11): 2214-21.
  15. Alijotas-Reig J., Ferrer-Oliveras R., Rodrigo-Anoro M.J., Farran-Codina I., Cabero-Roura L., Vilardell-Tarres M. Anti-beta(2)-glycoprotein-I and anti-phosphatidylserine antibodies in women with spontaneous pregnancy loss. Fertil. Steril. 2010; 93(7): 2330-6.
  16. Менжинская И.В., Кашенцева М.М., Ионанидзе Т.Б., Ванько Л.В., Сухих Г.Т. Спектр антифосфолипидных антител у женщин с привычным невынашиванием беременности и их диагностическое значение. Иммунология. 2016; 37(1): 4-9. [Menzhinskaya I.V., Kashentseva M.M., Ionanidze T.B., Van’ko L.V., Sukhikh G.T. Spectrum of antiphospholipid antibodies in women with recurrent pregnancy loss and their diagnostic value. Immunologiya/Immunology. 2016; 37(1): 4-9. (in Russian)]
  17. Saccone G., Berghella V., Maruotti G.M., Ghi T., Rizzo G., Simonazzi G. et al. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the pregnants study. Am. J. Obstet. Gynecol. 2017; 216(5): 525. e1-525. e12.
  18. Yelnik C.M., Urbanski G., Drumez E., Sobanski V., Maillard H., Lanteri A. et al. Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity. Lupus. 2017; 26(2): 163-9.
  19. Pengo V., Ruffati A., Legnani C., Gresele P., Barcellona D., Erba N. et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J. Thromb. Haemost. 2010; 8(2): 237-42.
  20. 20. Reynaud Q., Lega J.C., Mismetti P., Chapelle C., Wahl D., Cathébras P., Laporte S. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun. Rev. 2014; 13(6): 595-608.
  21. Kelchtermans H., Pelkmans L., de Laat L., Devreese K.M. IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. J. Thromb. Haemost. 2016; 14(8): 1530-48.
  22. de Laat B., Derksen R.H., Reber G., Musial J., Swadzba J., Bozic B. et al. An international multicentre-laboratory evaluation of a new assay to detect specifically lupus anticoagulants dependent on the presence of anti-beta2-glycoprotein autoantibodies. J. Thromb. Haemost. 2011; 9(1): 149-53.
  23. Ruffatti A., Del Ross T., Ciprian M., Cavazzana A., Grava C., Noventa F. et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann. Rheum. Dis. 2009; 68(3): 397-9.
  24. Bouvier S., Cochery-Nouvellon E., Lavigne-Lissalde G., Mercier E., Marchetti T., Balducchi J.P. et al. Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood. 2014; 123(3): 404-13.
  25. Mekinian A., Alijotas-Reig J., Carrat F., Costedoat-Chalumeau N., Ruffatti A., Lazzaroni M.G. et al. Refractory obstetrical antiphospholipid syndrome: Features, treatment and outcome in a European multicenter retrospective study. Autoimmun. Rev. 2017; 16(7): 730-4.
  26. Radin M., Cecchi I., Rubini E., Schreiber K., Roccatello D., Mahler M., Sciascia S. Prevalence and significance of anti-phosphatidylserine antibodies: a pooled analysis in 5992. Thromb. Res. 2018; 170: 28-31.
  27. Castanon A., Pierre G., Willis R., Harris E.N., Papalardo E., Romay-Penabad Z. et al. Performance evaluation and clinical associations of immunoassays that detect antibodies to negatively charged phospholipid other than cardiolipin. Am. J. Clin. Pathol. 2018; 149(5): 401-11.
  28. Sugi T. Kininogen-dependent antiphosphatidylethanolamine antibodies and autoantibodies to factor XII in patients with recurrent pregnancy loss. J. Obstet. Gynaecol. Res. 2013; 39(7): 1223-9.
  29. Conti F., Allessandri C., Sorice M., Capozzi A., Longo A., Garofalo T. et al. Thin-layer chromatography immunostaining in detecting anti-phospholipid antibodies in seronegative anti-phospholipid syndrome. Clin. Exp. Immunol. 2012; 167(3): 429-37.
  30. Sato Y., Sugi T., Sakai R. Autoantibodies to factor XII and kininogen-dependent antiphosphatidylethanolamine antibodies in patients with recurrent pregnancy loss augment platelet aggregation. Am. J. Reprod. Immunol. 2015;74(3): 279-89.
  31. Mehrani T., Petri M. Association of IgA anti-beta2 glycoprotein I with clinical and laboratory manifestations of systemic lupus erythematosus. J. Rheumatol. 2011; 38(1): 64-8.
  32. Murthy V., Willis R., Romay-Penabad Z., Ruiz-Limón P., Martínez-Martínez L.A., Jatwani S. et al. Value of isolated IgA anti-beta2-glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome. Arthritis Rheum. 2013; 65(12): 3186-93.
  33. Meijide H., Sciascia S., Sanna G., Khamashta M.A., Bertolaccini M.L. The clinical relevance of IgA anticardiolipin and IgA anti-β2 glycoprotein I antiphospholipid antibodies: a systematic review. Autoimmun. Rev. 2013; 12(3): 421-5.
  34. Rodriguez-Garcia V., Ioannou Y., Fernandez-Nebro A., Isenberg D.A., Giles I.P. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology (Oxford). 2015; 54(11): 2042-50.
  35. Ioannou Y., Zhang J.Y., Qi M., Gao L., Qi J.C., Yu D.M. et al. Novel assays of thrombogenic pathogenicity in the antiphospholipid syndrome based on the detection of molecular oxidative modification of the major autoantigen beta2-glycoprotein I. Arthritis Rheum. 2011; 63(9): 2774-82.
  36. Mahler M., Norman G.L., Meroni P.L., Khamashta M. Autoantibodies to domain 1 of beta 2 glycoprotein 1: a promising candidate biomarker for risk management in antiphospholipid syndrome. Autoimmun. Rev. 2012; 12(2): 313-7.
  37. de Laat B., Pengo V., Pabinger I., Musial J., Voskuyl A.E., Bultink I.E. et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J. Thromb. Haemost. 2009; 7(11): 1767-73.
  38. Andreoli L., Chighizola C.B., Nalli C., Gerosa M., Borghi M.O., Pregnolato F. et al. Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against β2 -glycoprotein I domain 1 and domain 4/5: ratio of anti-domain 1 to anti-domain 4/5 as a useful new biomarker for antiphospholipid syndrome. Arthritis Rheumatol. 2015; 67(8): 2196-204.
  39. Banzato A., Pozzi N., Frasson R., De Filippis V., Ruffatti A., Bison E. et al. Antibodies to Domain I of beta(2)Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS). Thromb. Res. 2011; 128(6): 583-6.
  40. Ulander V.M., Stefanovic V., Masuda J., Suzuki K., Hiilesmaa V., Kaaja R. Plasma levels of annexins IV and V in relation to antiphospholipid antibody status in women with a history of recurrent miscarriage. J. Thromb. Res. 2007; 120(6): 865-70.
  41. Singh N.K., Yadav D.P., Gupta A., Singh U., Godara M. Role of anti-annexin A5 in pathogenesis of hypercoagulable state in patients with antiphospholipid syndrome. Int. J. Rheum. Dis. 2013; 16(3): 325-30.
  42. Чепанов С.В., Шляхтенко Т.Н., Зайнулина М.С., Мирашвили М.И., Соколов Д.И., Сельков С.А. Антитела к аннексину V у женщин с привычным невынашиванием беременности. Акушерство и гинекология. 2014; 7: 29-32. [Chepanov S.V., Shlyahtenko T.N., Zajnulina M.S., Mirashvili M.I., Sokolov D.I., Sel’kov S.A. Antibodies to annexin V in women with recurrent pregnancy loss. Akusherstvo i ginekologiya/ Obstetrics and Gynecology. 2014; 7: 29-32. (in Russian)]
  43. Sater M.S., Finan R.R., Mustafa E., Al-Khateeb G.M. Anti-annexin V IgM and IgG autoantibodies and the risk of idiopathic recurrent spontaneous miscarriage. J. Reprod. Immunol. 2011; 89(1): 78-83.
  44. Bećarević M. The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome. J. Thromb. Thrombolysis. 2016; 42(4): 552-7.
  45. Rand J.H., Arslan A.A., Wu X.X., Wein R., Mulholland J., Shah M. et al. Reduction of circulating annexin A5 levels and resistance to annexin A5 anticoagulant activity in women with recurrent spontaneous pregnancy losses. Am. J. Obstet. Gynecol. 2006; 194(1): 182-8.
  46. Hunt B.J., Wu X.X., de Laat B., Arslan A.A., Stuart-Smith S., Rand J.H. Resistance to annexin A5 anticoagulant activity in women with histories for obstetric antiphospholipid syndrome. Am. J. Obstet. Gynecol. 2011; 205(5): 485. e17-23.
  47. Atsumi T., Amengual O., Yasuda S., Koike T. Antiprothrombin antibodies--are they worth assaying? Thromb. Res. 2004; 114(5-6): 533-8.
  48. Pengo V., Denas G., Bison E., Banzato A., Jose S.P., Gresele P. et al. Prevalence and significance of anti-prothrombin (aPT) antibodies in patients with Lupus Anticoagulant (LA). Thromb. Res. 2010; 126(2): 150-3.
  49. Žigon P., Čučnik S., Ambrožič A., Kveder T., Šemrl S.S., Rozman B., Božič B. Detection of antiphosphatidylserine/prothrombin antibodies and their potential diagnostic value. Clin. Dev. Immunol. 2013; 2013: 724592.
  50. Sanfelippo M.J., Joshi A., Schwartz S., Meister J.A., Goldberg J.W. Antibodies to phosphatidylserine/prothrombin complex in suspected antiphospholipid syndrome in the absence of antibodies to cardiolipin or beta-2-glycoprotein I. Lupus. 2013; 22(13): 1349-52.
  51. Sciascia S., Murru V., Sanna G., Roccatello D., Khamashta M.A., Bertolaccini M.L. Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities. J. Thromb. Haemost. 2012; 10(12): 2512-8.
  52. Sciascia S., Sanna G., Murru V., Roccatello D., Khamashta M.A., Bertolaccini M.L. Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb. Haemost. 2014; 111(2): 354-64.
  53. Amengual O., Forastiero R., Sugiura-Ogasawara M., Otomo K., Oku K., Favas C. et al. Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study. Lupus. 2017; 26(3): 266-76.
  54. 54. Kitaori T., Sugiura-Ogasawara M., Oku K., Papisch W., Ebara T., Ozaki Y. et al. Determination of clinically significant tests for antiphospholipid antibodies and cutoff levels for obstetric antiphospholipid syndrome. Lupus. 2015; 24(14): 1505-19.
  55. Latino J.O., Udry S., Wingeyer S.P., Romero D.F., Micone P., de Larrañaga G. What is the best time to assess the antiphospholipid antibodies (aPL) profile to better predict the obstetric outcome in antiphospholipid syndrome (APS) patients? Immunol. Res. 2018; 66(5): 577-83.
  56. Сидельникова В.М. Подготовка и ведение беременности у женщин с привычным невынашиванием: методическое пособие и клинические протоколы. М.: МЕДпресс-информ; 2010. 224с. [Sidel’nikova V.M. Preparation and management of pregnancy in women with habitual miscarriage: guidelines and clinical protocols. M.: MEDpress-inform; 2010. 224s. (in Russian)]
  57. Schreibera K., Radinc M., Sciascia S. Current insights in obstetric antiphospholipid syndrome. Women’s Health. 2017; 29(6): 397-403.
  58. Шляхтенко Т.Н., Алябьева Е.А., Аржанова О.Н., Сельков С.А., Плужникова Т.А., Чепанов С.В. Антифосфолипидный синдром при невынашивании беременности. Журнал акушерства и женских болезней. 2015; 64(5): 69-76. [Shlyahtenko T.N., Alyab’eva E.A., Arzhanova O.N., Sel’kov S.A., Pluzhnikova T.A., Chepanov S.V. Antiphospholipid syndrome in miscarriage. Zhurnal akusherstva i zhenskih boleznej/ Journal of obstetrics and women’s diseases. 2015; LXIV(issue 5): 69-76. (in Russian)]

Received 14.09.2018

Accepted 21.09.2018

About the Authors

Menzhinskaya, Irina V., PhD, senior researcher at the Clinical Immunology Laboratory, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: i_menzinskaya@oparina4.ru
Vanko, Lyudmila V., MD, professor, leading researcher at the Clinical Immunology Laboratory, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: LVanko@oparina4.ru

For citations: Menzhinskaya I.V., Vanko L.V. Antiphospholipid antibodies as diagnostic markers for obstetric antiphospholipid syndrome. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2019; (2): 5-12. (in Russian)
http://dx.doi.org/10.18565/aig.2019.2.5-12

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