Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
5-Year IF – 2.0, IF – 1.9, JCI (2024) – 0.43
Scopus CiteScore – 4.3
Q1 in SJR 2024, SJR score – 0.598, H-index: 49 (SJR)
ICV – 161.00; MNiSW – 70 pts
Initial editorial assessment and first decision within 24 h

ISSN 1899–5276 (print), ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 5, September-October, p. 729–733

Publication type: original article

Language: English

IgA Antiphospholipid Antibodies and Anti-Domain 1 of Beta 2 Glycoprotein 1 Antibodies are Associated with Livedo Reticularis and Heart Valve Disease in Antiphospholipid Syndrome

Marek Cieśla1,B,C,D, Ewa Wypasek1,2,B,C,D, Anetta Undas1,2,A,E,F

1 John Paul II Hospital, Cracow, Poland

2 Institute of Cardiology, Jagiellonian University School of Medicine, Cracow, Poland

Abstract

Background. . Antiphospholipid syndrome (APS) is an autoimmune disease associated with venous or arterial thrombosis and pregnancy loss, but also infrequently with non-criteria APS manifestations such as thrombocytopenia, livedo reticularis and heart valve disease. The occurrence of antiphospholipid antibodies is necessary to diagnose APS and includes the presence of lupus anticoagulant and anticardiolipin as well as anti-β2-glycoprotein I antibodies, both in IgM and/or IgG isotype.
Objectives. The aim of this study was to evaluate the associations between antiphospholipid antibodies including IgA isotype and IgG anti-domain I of β2-glycoprotein I (β-2GPI-D1) and non-criteria-related manifestations of APS.
Material and Methods. Thirty-three consecutive APS patients (26 women, 7 men, aged 44.1 ± 15 years), including 23 (69.7%) subjects with primary APS, were enrolled. Together with standard antiphospholipid antibodies, IgA anticardiolipin, IgA anti-β2-glycoprotein I and IgG anti-β-2GPI-D1 antibodies in serum samples were evaluated by chemiluminescence using the QUANTA Flash® System.
Results. Livedo reticularis (n = 8, 24.2%) was associated with increased levels of IgG anti-β-2GPI-D1 (p = 0.005), IgA anticardiolipin (p = 0.001) and IgA anti-β2-glycoprotein I (p = 0.002) antibodies. Heart valve disease (n = 9, 27.3%) was observed in patients with higher IgG anti-β-2GPI-D1 (p = 0.01). The associations of HVD with increased levels of IgA aCL and IgA anti-β-2GPI tended to be significant (p = 0.07). None of antiphospholipid antibodies showed association with thrombocytopenia (n = 6, 18.2%).
Conclusion. Our study suggests that increased IgA antiphospholipid antibodies and IgG anti-β-2GPI-D1 antibodies may be involved in the development of livedo reticularis and heart valve disease in APS patients.

Key words

antiphospholipid syndrome, beta 2 glycoprotein 1, domain 1, heart valve disease, livedo reticularis.

References (15)

  1. 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.
  2. Jeleniewicz R, Majdan M, Targońska-Stępniak B, Dryglewska M: Prevalence of antiphospholipid antibodies in rheumatoid arthritis patients and relationship with disease activity. Pol Arch Med Wewn 2012, 122, 480–486.
  3. Lakos G, Kiss E, Regëczy N, Tarján P, Soltész P, Zeher M, Bodolay E, Szakony S, Sipka S, Szegedi G: Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (beta2-GPI) antibodies: importance of IgA isotype. Clin Exp Immunol 1999, 117, 574–579.
  4. Marchetti T, Cohen M, Gris JC, de Moerloose P: Diagnosis and management of obstetrical antiphospholipid syndrome: where do we stand? Pol Arch Med Wewn 2013, 123, 713–720.
  5. Krause I, Lev S, Fraser A, Blank M, Lorber M, Stojanovich L, Rovensky J, Chapman J, Shoenfeld Y: Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome. Ann Rheum Dis 2005, 64, 1490–1493.
  6. de Groot PG, Urbanus RT: The future of antiphospholipid antibody testing. Semin Thromb Hemost 2013, 38, 412–420.
  7. 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, 4, 295–306.
  8. Andreoli L, Fredi M, Nalli C, Piantoni S, Reggia R, Dall’Ara F, Tincani A: Clinical Significance of IgA AntiCardiolipin and IgA Anti-β2Glycoprotein I Antibodies. Curr Rheumatol Rep 2013, 15, 343. doi: 10.1007/s11926- 013-0343-1.
  9. Sebastiani GD, Galeazzi M, Tincani A, Piette JC, Font J, Allegri F, Mathieu A, Smolen J, de Ramon Garrido E, Fernandez-Nebro A, Jedryka-Goral A, Papasteriades C, Morozzi G, Bellisai F, De Pitá O, Marcolongo R: Anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus. Prevalence and clinical associations. European Concerted Action on the Immunogenetics of SLE. Scand J Rheumatol 1999, 28, 344–351.
  10. Samarkos M, Davies KA, Gordon C, Loizou S: Clinical significance of IgA anticardiolipin and anti-β2-GPI antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Clin Rheumatol 2006, 25, 199–204.
  11. Mahler M, Norman GL, Meroni PL, 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, 313–317.
  12. de Laat B, Derksen RH, Urbanus RT, de Groot PG: IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood 2005, 105, 1540–1545.
  13. de Laat B, Pengo V, Pabinger I, Musial J, Voskuyl AE, Bultink IE, Ruffatti A, Rozman B, Kveder T, de Moerloose P, Boehlen F, Rand J, Ulcova-Gallova Z, Mertens K, de Groot PG: The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost 2009, 7, 1767–1773.
  14. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, de Groot PG: Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009, 7, 1737–1740.
  15. Toubi E, Krause I, Fraser A, Lev S, Stojanovich L, Rovensky J, Blank M, Shoenfeld Y: Livedo reticularis is a marker for predicting multi-system thrombosis in antiphospholipid syndrome. Clin Exp Rheumatol 2005, 23, 499–504.