- Original article
- Open access
- Published:
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)
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
Bick RL. Antiphospholipid thrombosis syndromes. Clin Appl Thromb Hemost 2001; 7:241–258.
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.
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.
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.
Atsumi T, Amengual O, Yasuda S, Koike T. Antiprothrombin antibodies— are they worth assaying?Thromb Res 2004; 114 (5–6): 533–538.
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.
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.
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.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.
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.
Harris EN, Pierangeli SS. Revisiting the anticardiolipin test and its standardization. Lupus 2002; 11:269–275.
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.
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.
Atsumi T, Koike T. Antiprothrombin antibody: why do we need more assays? Lupus 2010; 19:436–439.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
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/.
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.4103/1110-161X.123795