Skip to main content
Egyptian Rheumatology and Rehabilitation
Download PDF

Clinical significance of phospholipid-cofactor antibodies in patients with systemic lupus erythematosus-associated antiphospholipid syndrome

Egyptian Rheumatology and Rehabilitation volume 40, pages 188–192 (2013)Cite this article

Abstract

Objectives

To establish whether antibodies directed against phospholipid-binding plasma proteins such as β2-glycoprotein I (β2GPI), prothrombin (PT), and Annexin V (AnxV) constitute a risk factor for thrombosis in patients with systemic lupus erythematosus (SLE)-associated antiphospholipid syndrome (SLE/APS).

Patients and methods

A group of SLE patients (with and without APS) and patients with primary APS (PAPS) were included in this study. Fifteen patients with deep vein thrombosis but without antiphospholipid (aPL) antibodies, and another 15 age-matched and sex-matched apparently healthy individuals served as a control group. All patients were investigated for lupus anticoagulants and detection of anticardiolipin (aCL) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. Antibodies against β2GPI (IgG and IgM), PT (IgG and IgM), and AnxV (IgG) were also measured using the respective enzyme-linked immunosorbent assays.

Results

The study included 58 SLE patients (18 SLE/APS patients and 40 patients without APS) as well as 40 patients with PAPS, mean age 43 years (range: 18–74 years). IgG and/or IgM aCL antibodies were detected in all patients with PAPS (100%), whereas the prevalence rates of aPL-cofactor antibodies were as follows: 75% anti-β2GPI, 70% anti-PT, and 25% anti-AnxV antibodies. In SLE patients without APS, aCL antibodies were detected in 17.5%, anti-β2GPI antibodies in 20%, anti-AnxV antibodies in 20%, and anti-PT antibodies in 10% of patients. None of the antibodies measured were detected in deep vein thrombosis cases or healthy controls.

Conclusion

Measurement of antiphospholipid-cofactor antibodies in addition to the more widely used aCL and anti-β2GPI antibodies could be a useful prognostic marker for the risk of thrombosis in SLE/APS patients.

References

  1. Bick RL. Antiphospholipid thrombosis syndromes. Clin Appl Thromb Hemost 2001; 7:241–258.

    CAS  Article  Google Scholar 

  2. Soltesz P, Veres K, Lakos G, Kiss E, Muszbek L, Szegedi G. Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients. Lupus 2003; 12:302–307.

    CAS  Article  Google Scholar 

  3. De Laat B, Mertens K, de Groot PG. Mechanisms of disease: antiphospholipid antibodies—from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol 2008; 4:192–199.

    Article  Google Scholar 

  4. Oosting JD, Derksen RH, Bobbink IW, Hackeng TM, Bouma BN, de Groot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood 1993; 81:2618–2625.

    CAS  Article  Google Scholar 

  5. Atsumi T, Amengual O, Yasuda S, Koike T. Antiprothrombin antibodies— are they worth assaying?Thromb Res 2004; 114 (5–6): 533–538.

  6. Van Heerde WL, Lap P, Schoormans S, de Groot PG, CPM Reutelingsperger, Vroom TM. Localization of annexin A5 in human tissue. Annexins 2004; 1:37–43.

    Google Scholar 

  7. De Laat B, RHWM Derksen, Mackie IJ, Roest M, Schoormans S, Woodhams BJ, et al. Annexin A5 polymorphism (-1C→T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome. Ann Rheum Dis 2006; 65:1468–1472.

    Article  Google Scholar 

  8. Rand JH, Wu XX, Quinn AS, Chen PP, McCrae KR, Bovill EG, et al. 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.

    CAS  Article  Google Scholar 

  9. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  11. Harris EN, Pierangeli SS. Revisiting the anticardiolipin test and its standardization. Lupus 2002; 11:269–275.

    CAS  Article  Google Scholar 

  12. Reber G, Tincani A, Sanmarco M, de Moerloose P, Boffa MC. Proposals for the measurement of anti-β2-glycoprotein I antibodies. Standardization group of the European Forum on Antiphospholipid Antibodies. J Thromb Haemost 2004; 2:1860–1862.

    CAS  PubMed  Google Scholar 

  13. Bizzaro N, Tonutti E, Villalta D, Tampoia M, Tozzoli R. Prevalence and clinical correlation of anti-phospholipid-binding protein antibodies in anticardiolipin-negative patients with systemic lupus erythematosus and women with unexplained recurrent miscarriages. Arch Pathol Lab Med 2005; 129:61–68.

    PubMed  Google Scholar 

  14. Atsumi T, Koike T. Antiprothrombin antibody: why do we need more assays? Lupus 2010; 19:436–439.

    CAS  Article  Google Scholar 

  15. Theodoridou A, Bertolaccini M, Hamid C, Khamashta MA, Hughes GRV. The value of testing for antiphospholipid antibodies, other than aCL and LA, in systemic lupus erythematosus patients with thrombosis. Arthritis Rheum 2002; 46 (Suppl): S50.

  16. Hsieh K, Knöbl P, Rintelen C, Kyrle PA, Quehenberger P, Bialonczyk C, et al. Is the determination of anti-beta2 glycoprotein I antibodies useful in patients with venous thromboembolism without the antiphospholipid syndrome? Br J Haematol 2003; 123:490–495.

    CAS  Article  Google Scholar 

  17. Puurunen M, Vaarala O, Julkunen H, Aho K, Palosuo T. Antibodies to phospholipid-binding plasma proteins and occurrence of thrombosis in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 1996;80:16–22.

    CAS  Article  Google Scholar 

  18. Bertolaccini ML, Atsumi T, Khamashta MA, Amengual O, Hughes GRV. Autoantibodies to human prothrombin and clinical manifestations in 207 patients with systemic lupus erythematosus. J Rheumatol 1998; 25:1104–1108.

    CAS  PubMed  Google Scholar 

  19. Muñoz Rodríguez FJ, Reverter JC, Font J, Tàssies D, Cervera R, Espinosa G, et al. Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome. Haematologica 2000; 85:632–637.

    PubMed  Google Scholar 

  20. Nojima J, Kuratsune H, Suehisa E, Futsukaichi Y, Yamanishi H, Machii T, et al. Anti-prothrombin antibodies combined with lupus anticoagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus. Br J Haematol 2001; 114:647–654.

    CAS  Article  Google Scholar 

  21. Horbach DA, van Oort E, Donders RC, Derksen RH, de Groot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythematosus. Comparison between different assays for the detection of antiphospholipid antibodies. Thromb Haemost 1996; 76:916–924.

    CAS  PubMed  Google Scholar 

  22. Pengo V, Biasiolo A, Brocco T, Tonetto S, Ruffatti A. Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies. Thromb Haemost 1996; 75:721–724.

    CAS  Article  Google Scholar 

  23. Swadzba J, De Clerck LS, Stevens WJ, Bridts CH, Van Cotthem KA, Musial J, et al. Anticardiolipin, anti-β2-glycoprotein I, antiprothrombin antibodies and lupus anticoagulant in patients with systemic lupus erythematosus with a history of thrombosis. J Rheumatol 1997; 24:1710–1715.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology and Rehabilitation, Mansoura Faculty of Medicine, Mansoura University, 335111, Mansoura, Egypt

    Shereen A. Machaly MD

  2. Department of General Surgery, Vascular Surgery Unit, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Hesham A. Sharaf El-Din

Authors
  1. Shereen A. Machaly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hesham A. Sharaf El-Din
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shereen A. Machaly MD.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Cite this article

Machaly, S.A., Sharaf El-Din, H.A. Clinical significance of phospholipid-cofactor antibodies in patients with systemic lupus erythematosus-associated antiphospholipid syndrome. Egypt Rheumatol Rehabil 40, 188–192 (2013). https://doi.org/10.4103/1110-161X.123795

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/1110-161X.123795

Keywords

  • anti-Annexin V
  • antiphospholipid syndrome
  • antiprothrombin antibodies
  • anti-β2-glycoprotein I