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Current Rheumatology Reports
Published in: Current Rheumatology Reports 7/2013

01-07-2013 | ANTIPHOSPHOLIPID SYNDROME (RAS ROUBEY, SECTION EDITOR)

Clinical Significance of IgA Anti-Cardiolipin and IgA Anti-β2Glycoprotein I Antibodies

Authors: Laura Andreoli, Micaela Fredi, Cecilia Nalli, Silvia Piantoni, Rossella Reggia, Francesca Dall’Ara, Franco Franceschini, Angela Tincani

Published in: Current Rheumatology Reports | Issue 7/2013

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Abstract

IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-β2glycoprotein I antibodies (anti-β2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-β2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-β2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.
Literature
1.
Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis. 2006;295–306.
2.
•• Bertolaccini ML, Amengual O, Atsumi T, et al. 'Non-criteria' aPL tests: report of a task force and preconference workshop at the 13th International Congress on Antiphospholipid Antibodies, Galveston, TX, USA, April 2010. Lupus. 2011;20:191–205. The literature on ‘non-criteria’ aPL (including IgA aPL) has been reviewed in an evidence-based manner by a task force of worldwide scientists. Findings, conclusions and recommendations are summarized in this report.PubMedCrossRef
3.
•• Lakos G, Favaloro EJ, Harris EN, et al. International consensus guidelines on anticardiolipin and anti-β2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012;64(1):1–10. This is the most up-to-date and detailed report on the consensus guidelines on the recommended best practices for immunoassays for the measurement of aCL and anti-β2GPI antibodies.PubMedCrossRef
4.
• Meijide H, Sciascia S, Sanna G, et al. The clinical relevance of IgA anticardiolipin and IgA anti-β2 glycoprotein I antiphospholipid antibodies: A systematic review. Autoimmun Rev. 2012 [Epub ahead of print]. A comprehensive review of the literature on IgA aPL between January 1990 and April 2012. Relevant articles have been divided and analyzed in 3 subgroups: (1) studies that showed usefulness of IgA aPL testing in autoimmune population; (2) studies with no clinical associations of IgA aPL in autoimmune population; and (3) studies of IgA aPL in other non-autoimmune disorders.
5.
Uthman I, Khamashta M. Ethnic and geographical variation in antiphospholipid (Hughes) syndrome. Ann Rheum Dis. 2005;64:1671–6.PubMedCrossRef
6.
Weidmann CE, Wallace DJ, Peter JB, et al. Studies of IgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus. J Rheumatol. 1988;15:74–9.PubMed
7.
Kalunian KC, Peter JB, Middlekauff HR, et al. Clinical significance of a single test for anti-cardiolipin antibodies in patients with systemic lupus erythematosus. Am J Med. 1988;85:602–8.PubMedCrossRef
8.
Alarcón-Segovia D, Delezé M, Oria CV. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore). 1989;68:353–65.
9.
Lopez LR, Santos M, Espinoza LR, et al. Clinical significance of Immunoglobulin A versus Immnunoglobulin G and M Anticardiolipin antibodies in Patients with Systemic Lupus Erythematosus: correlation with thrombosis, thrombocytopenia and recurrent abortion. Coag Transf Med. 1991;98:449–54.
10.
Molina JF, Gutierrez-Ureña S, Molina J, et al. Variability of anticardiolipin antibody isotype distribution in 3 geographic populations of patients with systemic lupus erythematosus. J Rheumatol. 1997;24:291–6.PubMed
11.
Tajima C, Suzuki Y, Mizushima Y, Ichikawa Y. Clinical significance of immunoglobulin A antiphospholipid antibodies: possible association with skin manifestations and small vessel vasculitis. J Rheumatol. 1998;25:1730–6.PubMed
12.
Cucurull E, Gharavi AE, Diri E, et al. IgA anticardiolipin and anti-beta2-glycoprotein I are the most prevalent isotypes in African American patients with systemic lupus erythematosus. Am J Med Sci. 1999;318:55–60.PubMedCrossRef
13.
Hanly JG, Hong C, Smith S, et al. A prospective analysis of cognitive dysfunction and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum. 1999;42:728–34.PubMedCrossRef
14.
Sebastiani GD, Galeazzi M, Tincani A, et al. 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;28:344–51.PubMedCrossRef
15.
Samarkos M, Davies KA, Gordon C, et al. 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.PubMedCrossRef
16.
Shen YM, Lee R, Frenkel E, Sarode R. IgA antiphospholipid antibodies are an independent risk factor for thromboses. Lupus. 2008;17:996–1003.PubMedCrossRef
17.
Gharavi AE, Harris EN, Asherson RA, Hughes GR. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis. 1987;46:1–6.PubMedCrossRef
18.
Wong KL, Liu HW, Ho K, et al. Anticardiolipin antibodies and Lupus anticoagulant in Chinese patients with systemic lupus erythematosus. J Rheumatol. 1991;18:1187–92.PubMed
19.
Loizou S, Cofiner C, Weetman AP, et al. Immunoglobulin class and IgG subclass distribution of anticardiolipin antibodies in patients with systemic lupus erythematosus and associated disorders. Clin Exp Immunol. 1992;90:434–9.PubMedCrossRef
20.
Merkel PA, Chang YC, Pierangeli S, et al. The Prevalence and Clinical Associations of Anticardiolipin Antibodies in a Large Inception Cohort of Patients with Connective Tissue Diseases. Am J Med. 1996;101:576–83.PubMedCrossRef
21.
Selva-O'Callaghan A, Ordi-Ros J, Monegal-Ferran F, et al. IgA anticardiolipin antibodies–relation with other antiphospholipid antibodies and clinical significance. Thromb Haemost. 1998;79:282–5.PubMed
22.
Fanopoulos D, Teodorescu MR, Varga J, et al. High frequency of abnormal levels of IgA anti-beta-glycoprotein I in patients with systemic lupus erythematosus: relationship with antiphospholipid syndrome. J Rheumatol. 1998;25:675–850.PubMed
23.
Lakos G, Kiss E, Regéczy N, et al. Isotype distribution and clinical relevance of anti-β2-glycoprotein I (β2-GPI) antibodies: importance of IgA isotype. Clin Exp Immunol. 1999;117:574–9.PubMedCrossRef
24.
Greco TP, Amos MD, Conti-Kelly AM, et al. Testing for the antiphospholipid syndrome: importance of IgA anti-beta 2-glycoprotein I. Lupus. 2000;9:33–41.PubMedCrossRef
25.
Spadaro A, Riccieri V, Terracina S, et al. Class specific rheumatoid factors and antiphospholipid syndrome in systemic lupus erythematosus. Lupus. 2000;9:56–60.PubMedCrossRef
26.
Shrivastava A, Dwivedi S, Aggarwal A, et al. Anti-cardiolipin and anti-beta 2 glycoprotein I antibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizure. Lupus. 2001;10:45–50.PubMedCrossRef
27.
Bertolaccini ML, Atsumi T, Escuedero Contreras A, et al. The value of IgA antiphospholipid testing for diagnosis of antiphospholipid (Hughes) syndrome in systemic lupus erythematosus. J Rheumatol. 2001;28:2637–43.PubMed
28.
Lee RM, Branch DW, Silver RM. Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death. Am J Obstet Gynecol. 2001;185:748–53.PubMedCrossRef
29.
Carmo-Pereira S, Bertolaccini ML, Escudero-Contreras A, et al. Value of IgA anticardiolipin and anti-beta2-glycoprotein I antibody testing in patients with pregnancy morbidity. Ann Rheum Dis. 2003;62:540–3.PubMedCrossRef
30.
• Mehrani T, Petri M. Association of IgA Anti-β2 glycoprotein I with clinical and laboratory manifestations of systemic lupus erythematosus. J Rheumatol. 2011;38:64–8. In a large cohort of SLE patients, it has been demonstrated that IgA anti-β2GPI antibodies are associated with venous thrombosis and other clinical and laboratory features typical of SLE and APS.PubMedCrossRef
31.
Diri E, Cucurull E, Gharavi AE, et al. Antiphospholipid (Hughes’) syndrome in african-americans: IgA aCl and aβ2 glycoprotein-I is the most frequent isotype. Lupus. 1999;8:263–8.PubMedCrossRef
32.
Picillo U, Migliaresi S, Marcialis MR, et al. Clinical significance of anticardiolipin antibodies in patients with systemic sclerosis. Autoimmunity. 1995;20:1–7.PubMedCrossRef
33.
Tokay S, Direskeneli H, Yurdakul S, Akoglu T. Anticardiolipin antibodies in Behçet's disease: a reassessment. Rheumatology (Oxford). 2001;40:192–5.CrossRef
34.
Lamprecht P, deGroot K, Schnabel A, et al. Anticardiolipin antibodies and antibodies to beta(2)-glycoprotein I in patients with Wegener's granulomatosis. Rheumatology (Oxford). 2000;39:568–70.CrossRef
35.
Gupta M, Johann-Liang R, Bussel JB, et al. Elevated IgA and IgM anticardiolipin antibodies in acute Kawasaki disease. Cardiology. 2002;97:180–2.PubMedCrossRef
36.
Yang YH, Huang MT, Lin SC, et al. Increased transforming growth factor-beta (TGF-beta)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch-Schönlein purpura. Clin Exp Immunol. 2000;122:285–90.PubMedCrossRef
37.
Kawakami T, Yamazaki M, Mizoguchi M, Soma Y. High titer of serum antiphospholipid antibody levels in adult Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis. Arthritis Rheum. 2008.15;59:561–7.
38.
Burden AD, Tillman DM, Foley P, Holme E. IgA class anticardiolipin antibodies in cutaneous leukocytoclastic vasculitis. J Am Acad Dermatol. 1996;35:411–5.PubMedCrossRef
39.
Klok AM, Geertzen R, Rothova A, et al. Anticardiolipin antibodies in uveitis. Curr Eye Res. 1992;11:209–13.PubMedCrossRef
40.
Mankai A, Achour A, Thabet Y, et al.: Anti-cardiolipin and anti-beta 2-glycoprotein I antibodies in celiac disease. Autoimmun Rev. 2011 [Epub ahead of print].
41.
Gabeta S, Norman GL, Gatselis N, et al. IgA Anti-b2GPI Antibodies in patients with autoimmune liver disease. J Clin Immunol. 2008;28:501–11.PubMedCrossRef
42.
Magro CE, Guidolin F, Bezerra NF, et al. Livedo reticularis with ulcers in a pateint with IgA anticardiolipin antibodies. An Bras Dermatol. 2005;80:538–9.CrossRef
43.
Wilson WA, Morgan Ost C, Barton EN, et al. IgA antiphospholipid antibodies in HTLV-1 associated tropical spastic paraparesis. Lupus. 1995;4:138–41.PubMedCrossRef
44.
Yoon KH, Wong A, Shakespeare T, Sivalingam P. High prevalence of antiphospholipid antibodies in Asian cancer patients with thrombosis. Lupus. 2003;12:112–6.PubMedCrossRef
45.
Bernardini I, Pugliese L, Pacifico E, et al. IgA anticardiolipin in patients with gastroenteric Tumor. Scholary Research Exchange 2009;1–4.
46.
Tsutsumi A, Matsuura E, Ichikawa K, et al. Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum. 1996;39:1466–74.PubMedCrossRef
47.
Lee SS, Cho ML, Joo YS, et al. Isotypes of anti-beta2-glycoprotein I antibodies: association with thrombosis in patients with systemic lupus erythematosus. J Rheumatol. 2001;28:520–4.PubMed
48.
Danowski A, Kickler TS, Petri M. Anti-beta2-glycoprotein I: prevalence, clinical correlations, and importance of persistent positivity in patients with antiphospholipid syndrome and systemic lupus erythematosus. J Rheumatol. 2006;33:1775–9.PubMed
49.
Karpouzas GA, Moran RC, Harris C, Hahn BH. B2-glycoprotein-I IgA antibodies (a-b2GPI IgA Ab) but not the IgG a-B2 and IgG a-cardiolipin listed in Sydney criteria predispose to vascular events in Hispanics with SLE. Arthritis Rheum. 2009;60:S479 [abstract 1276].
50.
• Sweiss NJ, Bo R, Kapadia R, et al. IgA anti-beta2-glycoprotein I autoantibodies are associated with an increased risk of thromboembolic events in patients with systemic lupus erythematosus. PLoS One. 2010;5:e12280. An interesting cohort of patients with isolated IgA anti-β2GPI antibodies and the description of clinical associations in patients with SLE.PubMedCrossRef
51.
Guerin J, Casey E, Feighery C, Jackson J. Anti-Beta 2-glycoprotein I antibody isotype and IgG subclass in antiphospholipid syndrome patients. Autoimmunity. 1999;31:109–16.PubMedCrossRef
52.
Bruce IN, Clark-Soloninka CA, Spitzer KA, et al. Prevalence of antibodies to beta2-glycoprotein I in systemic lupus erythematosus and their association with antiphospholipid antibody syndrome criteria: a single center study and literature review. J Rheumatol. 2000;27:2833–7.PubMed
53.
Yamada H, Tsutsumi A, Ichikawa K, et al. IgA-class anti-beta2-glycoprotein I in women with unexplained recurrent spontaneous abortion. Arthritis Rheum. 1999;42:2727–8.PubMedCrossRef
54.
Kumar S, Papalardo E, Sunkureddi P, et al. Isolated elevation of IgA anti-beta2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients. Lupus. 2009;18:1011–4.PubMedCrossRef
55.
Abinader A, Hanly AJ, Lozada CJ. Catastrophic antiphospholipid syndrome associated with anti-beta-2-glycoprotein I IgA. Rheumatology (Oxford). 1999;38:84–5.CrossRef
56.
Boin F, Franchini S, Colantuoni E, et al. Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients. Arthritis Rheum. 2009;60:2480–9.PubMedCrossRef
57.
Staub HL, Franck M, Ranzolin A., et al. IgA antibodies to beta2-glycoprotein I and atherosclerosis. Autoimmun Rev. 2006:104–6.
58.
Kahles T, Humpich M, Steinmetz H, et al. Phosphatidylserine IgG and beta-2-glycoprotein I IgA antibodies may be a risk factor for ischaemic stroke. Rheumatology (Oxford). 2005;44:1161–5.CrossRef
59.
Borges RB, Bodanese LC, Mühlen CA, et al. Anti-beta2-glycoprotein I autoantibodies and metabolic syndrome. Arq Bras Cardiol. 2011;96:272–6.PubMedCrossRef
60.
Serrano A, García F, Serrano M, et al. IgA antibodies against β2 glycoprotein I in hemodialysis patients are an independent risk factor for mortality. Kidney Int. 2012;81:1239–44.PubMedCrossRef
61.
Holc I, Hojs R, Cikeš N, et al. Antiphospholipid antibodies and atherosclerosis: insights from rheumatoid arthritis–a five-year follow-up study. Immunobiology. 2011;216:1331–7.PubMedCrossRef
62.
Iverson GM, von Mühlen CA, Staub HL, et al. Patients with atherosclerotic syndrome, negative in anti-cardiolipin assays, make IgA autoantibodies that preferentially target domain 4 of beta2-GPI. J Autoimmun. 2006;27:266–71.PubMedCrossRef
63.
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. [Epub ahead of print]
64.
Martinez-Martinez LA, Aguilar-Valenzuela R, Seif AM, et al. Do clinically relevant IgA-Anti-B2glycoprotein I (anti-B2GPI) Antibodies bind domain IV/V of β2GPI? Arthritis Rheum. 2009;60:S478 [abstract 1274].
65.
Akhter E, Binder W, Shums Z, et al. Utility of anti-phosphatidilserine/prothrombin and IgA Antiphospholipid assays in antiphospholipid syndrome. Arthritis Rheum. 2010;62:S5 [abstract 14].
66.
Pierangeli SS, Liu XW, Barker JH, et al. Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome. Thromb Haemost. 1995;74:1361–7.PubMed
67.
Ruiz-Limon P, Romay-Penabad Z, Carrera Marin AL, et al. IgA anti-β2glycoprotein I antibodies are pathogenetic in a mouse model of APS. Arthritis Rheum. 2012;64:S742 [abstract 1731].
68.
•• Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677–86. The updated classification criteria for SLE proposed by the international group SLICC have included for the first time IgA aCL and IgA anti-β2GPI as valid tests for the definition of SLE.PubMedCrossRef
Metadata
Title
Clinical Significance of IgA Anti-Cardiolipin and IgA Anti-β2Glycoprotein I Antibodies
Authors
Laura Andreoli
Micaela Fredi
Cecilia Nalli
Silvia Piantoni
Rossella Reggia
Francesca Dall’Ara
Franco Franceschini
Angela Tincani
Publication date
01-07-2013
Publisher
Springer US
Published in
Current Rheumatology Reports / Issue 7/2013
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-013-0343-1

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