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The IgM isotype of anti-annexin A5 antibodies and multiple positivity of conventional antiphospholipid antibodies: increasing the number of clinical manifestations of primary antiphospholipid syndrome

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Abstract

We evaluated the importance of anti-annexin A5 antibodies (aanxA5 Abs) for clinical (thrombosis and/or recurrent pregnancy loss) and serologic (presence of antiphospholipid antibodies: lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2 glycoprotein I (aβ2GPI) antibodies) features of patients with primary antiphospholipid syndrome (PAPS). Our study included 70 patients with PAPS according to the international consensus criteria for APS. The mean age of the analyzed patients was 45.97 ± 12.72. The disease duration above 5 years was present in 31/70 of patients. Concentrations of analyzed antibodies were measured by ELISA. Cutoff values were set in accordance to the manufacturers’ recommendations. History of recurrent pregnancy loss was associated with double positivity for aanxA5 IgM and LA (χ 2 = 4.000, P = 0.046) and triple positivity for aanxA5 IgM + LA + aβ2GPI IgM (χ 2 = 4.168, P = 0.041). Venous thromboses were associated with triple positivity for aanxA5 IgM + aCLIgG + aβ2GPI IgM (χ 2 = 3.965, P = 0.046). The IgG isotype of aanxA5 Abs was in positive correlation with aCL Abs of the IgG (r = 0.310, P = 0.009) and IgM (r = 0.254, P = 0.034) isotype. The presence of the clinical manifestations of PAPS is increasing with the number of positive conventional aPL and the IgM aanxA5 Abs tests. This new combination of Abs is beneficial even when the number of patients with positivity for aanxA5 Abs is low. This is important in further detection of patients prone to recurrence of thrombotic episodes.

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References

  1. van den Hoogen LL, van Roon JAG, Radstake TRDJ, Fritsch-Stork RDE, Derksen RHWM (2015) Delineating the deranged immune system in the antiphospholipid syndrome. Autoimmun Rev. doi:10.1016/j.autrev.2015.08.011

    PubMed  Google Scholar 

  2. Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R et al (2014) 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev 13:917–930

    Article  PubMed  Google Scholar 

  3. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 4:295–306

    Article  CAS  PubMed  Google Scholar 

  4. Pengo V, Banzato A, Denas G et al (2013) Correct laboratory approach to APS diagnosis and monitoring. Autoimmun Rev 12:832–834

    Article  CAS  PubMed  Google Scholar 

  5. Forastiero R (2014) Multiple antiphospholipid antibodies positivity and antiphospholipid syndrome criteria re-evaluation. Lupus 23(12):1252–4

    Article  CAS  PubMed  Google Scholar 

  6. Hernández-Molina G, Espericueta-Arriola G, Cabral AR (2013) The role of lupus anticoagulant and triple marker positivity as risk factors for rethrombosis in patients with primary antiphospholipid syndrome. Clin Exp Rheumatol 31(3):382–8

    PubMed  Google Scholar 

  7. Nayfe R, Uthman I, Aoun J, Aldin ES, Merashil M, Khamashta MA (2013) Seronegative antiphospholipid syndrome. Rheumatology 52:1358–1367

    Article  PubMed  Google Scholar 

  8. de Laat B, Wu XX, van Lummel M, Derksen RHWM, de Groot PG, Rand JH (2007) Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5. Blood 109:1490–4

    Article  PubMed  Google Scholar 

  9. Brandt JT, Triplett DA, Alving B, Scharrer J (1995) Criteria for the diagnosis of lupus anticoagulants: an update on behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipd Antibody of the Scientific and Standardisation Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 74(4):1185–90

    CAS  PubMed  Google Scholar 

  10. Galli M, Luciani D, Bertolini G, Barbui T (2003) Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 101(5):1827–32

    Article  CAS  PubMed  Google Scholar 

  11. Forastiero R, Martinuzzo M, Pombo G, Puente D, Rossi A, Celebrin L et al (2005) A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and a risk of thrombosis. J Thromb Haemost 3(6):1231–8

    Article  CAS  PubMed  Google Scholar 

  12. Del Ross T, Ruffatti A, Cuffaro S, Tonello M, Calliagaro A, Favaro M et al (2015) The clinical relevance of the IgM isotype of antiphospholipid antibodies in the vascular antiphospholipid syndrome. Thromb Res. doi:10.1016/j.thromres.2015.08.019

    PubMed  Google Scholar 

  13. Nasef A, Ibrahim M, Riad N, Mousa S (2014) Plasma annexin A5, anti-annexin A5 antibodies and annexin A5 polymorphism in Egyptian female patients with systemic lupus erythematosus and antiphospholipid syndrome. Clin Lab 60(1):133–7

    CAS  PubMed  Google Scholar 

  14. Gris JC, Bouvier S (2013) Antiphospholipid syndrome: looking for a refocusing. Thromb Res 131(1):S28–S31

    Article  CAS  PubMed  Google Scholar 

  15. De Laat B, Derksen RHWM, Mackie IJ et al (2006) Annexin A5 polimorphism (−1C > T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome. Ann Rheum Dis 65(11):1468–72

    Article  PubMed  PubMed Central  Google Scholar 

  16. Amaral M, Favas C, Delgado Alves J (2010) Persistency of low levels of anticardiolipin and anti-beta2 glycoprotein 1 in thrombosis. Eur J Intern Med 21:101–103

    Article  CAS  PubMed  Google Scholar 

  17. Mekinian A, Loire-Berson P, Nicaise-Roland P, Lachassinne E, Stirnrmann J, Boffa MC et al (2012) Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels. J Reprod Immunol 94:222–226

    Article  PubMed  Google Scholar 

  18. Boffa MC, Boinot C, De Carolis S, Rovere-Querini P, Aurousseau MH, Allegri F et al (2009) Laboratory criteria of the obstetrical antiphospholipid syndrome. Data from a multicentric prospective European women cohort. Thromb Haemost 102:25–28

    CAS  PubMed  Google Scholar 

  19. Pengo V (2011) Antiphospholipid syndrome: interpretation of laboratory data. J Thromb Haemost 9(2):402–3

    Article  CAS  PubMed  Google Scholar 

  20. Kist WJ, Janssen NG, Kalk JJ, Hague WM, Dekker GA, de Vries JL (2008) Thrombophilias and adverse pregnancy outcome—a confounded problem. Thromb Haemost 99:77–85

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank all the patients who participated in this study and our colleagues from numerous clinics in Serbia.

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Correspondence to Mirjana Bećarević.

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All procedures performed in our study were in accordance with Helsinki Declaration (and its later amendments) and with the ethical standards of the institutional ethical committee. Informed consent was obtained from all individual participants included in the study.

Funding

This work was supported by research grant numbers 175041 and TR 32040 for 2011–2015, issued by the Ministry of Science of the Republic of Serbia. Also, the present work was supported by the Ministry of Science and Education of the Republic of Serbia on the basis of contract no. 175036.

The funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit this article for publication.

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Bećarević, M., Stojanović, L., Ignjatović, S. et al. The IgM isotype of anti-annexin A5 antibodies and multiple positivity of conventional antiphospholipid antibodies: increasing the number of clinical manifestations of primary antiphospholipid syndrome. Clin Rheumatol 35, 1361–1365 (2016). https://doi.org/10.1007/s10067-016-3230-0

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  • DOI: https://doi.org/10.1007/s10067-016-3230-0

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