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Semin Thromb Hemost 2018; 44(05): 466-474
DOI: 10.1055/s-0037-1603936
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prevalence and Thrombotic Risk Assessment of Anti-β2 Glycoprotein I Domain I Antibodies: A Systematic Review

Massimo Radin
1   Center of Research of Immunopathology and Rare Diseases - Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy
,
Irene Cecchi
1   Center of Research of Immunopathology and Rare Diseases - Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy
,
Dario Roccatello
1   Center of Research of Immunopathology and Rare Diseases - Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy
,
Pier Luigi Meroni
2   Department of Clinical Sciences and Community Health, University of Milan, Laboratory of Immuno-Rheumatology Research, Istituto Auxologico Italiano, Milan, Italy
,
Savino Sciascia
1   Center of Research of Immunopathology and Rare Diseases - Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, and SCDU Nephrology and Dialysis, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy
› Institutsangaben Funding None.
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Publikationsverlauf

Publikationsdatum:
04. August 2017 (online)

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Abstract

Background To date, the exact prevalence of anti-β2 glycoprotein I domain I (anti-β2GPI-DI) antibodies in patients with antiphospholipid syndrome (APS) and their role when assessing thrombosis risk is uncertain.

Objectives To estimate the prevalence of anti-β2GPI-DI in patients with APS and to determine whether anti-β2GPI-DI-positive individuals are at greater risk of thrombosis, as compared with individuals without anti-β2GPI-DI, by systematically reviewing the literature.

Methods A detailed literature search was applied a priori to Ovid MEDLINE In-Process and Other Non-Indexed Citation 1986 to present and to abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP ) Annual Meetings (2011–2015).

Results A total of 11 studies, including 1,585 patients, were analyzed. Patients were distributed as follow: 1,218 patients APS (45.4% anti-β2GPI-DI-positive; in more detail: 504 primary APS [55.4% anti-β2GPI-DI-positive], 192 secondary APS [43.2% anti-β2GPI-DI-positive], and 522 not specified), 318 with systemic lupus erythematosus (SLE; 26.7% anti-β2GPI-DI-positive), 49 asymptomatic carriers of antiphospholipid antibodies (aPL) (30.6% anti-β2GPI-DI-positive), and 1,859 healthy controls. When considering the five studies eligible for thrombotic risk assessment, four studies found a significant association of anti-β2GPI-DI-positivity with thrombotic events, whereas one study found no predictive correlation with thrombosis (overall odds ratio [OR] for pooled data: 1.99; 95% confidence interval [CI]: 1.52–2.6; p < 0.0001).

Conclusion We report an overall estimated median prevalence of anti-β2GPI-DI antibodies of 44.3% in patients with APS and/or SLE and a significantly higher prevalence among patients with APS compared with SLE alone. Anti-β2GPI-DI antibodies might represent a promising tool when assessing thrombotic risk in patients with APS.

Keywords

antiphospholipid syndrome - antiphospholipid antibodies - β2 glycoprotein I domain - non-criteria aPL - thrombosis

Author Contributions

M.R. and I.C. searched the literature, assisted with the organization of the manuscript, interpreted and collected data, and wrote and edited the review. P.L.M., D.R., and S.S. interpreted and collected data, helped to design the figures and panel, and wrote and edited the review.


 

  • References

  • 1 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
    CrossrefPubMedGoogle Scholar
  • 2 Meroni PL. Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools. Lupus 2016; 25 (08) 905-910
    CrossrefPubMedGoogle Scholar
  • 3 Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol 2011; 7 (06) 330-339
    CrossrefPubMedGoogle Scholar
  • 4 Raschi E, Chighizola CB, Grossi C. , et al. β2-glycoprotein I, lipopolysaccharide and endothelial TLR4: three players in the two hit theory for anti-phospholipid-mediated thrombosis. J Autoimmun 2014; 55: 42-50
    CrossrefPubMedGoogle Scholar
  • 5 Filippidou N, Krashias G, Pericleous C. , et al. The association between IgG and IgM antibodies against cardiolipin, β2-glycoprotein I and domain I of β2-glycoprotein I with disease profile in patients with multiple sclerosis. Mol Immunol 2016; 75: 161-167
    CrossrefPubMedGoogle Scholar
  • 6 Ambrozic A, Avicin T, Ichikawa K. , et al. Anti-beta(2)-glycoprotein I antibodies in children with atopic dermatitis. Int Immunol 2002; 14 (07) 823-830
    CrossrefPubMedGoogle Scholar
  • 7 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 (02) 313-317
    CrossrefPubMedGoogle Scholar
  • 8 Pengo V, Ruffatti A, Tonello M. , et al. Antibodies to domain 4/5 (Dm4/5) of β2-glycoprotein 1 (β2GP1) in different antiphospholipid (aPL) antibody profiles. Thromb Res 2015; 136 (01) 161-163
    CrossrefPubMedGoogle Scholar
  • 9 de Laat B, Pengo V, Pabinger I. , et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost 2009; 7 (11) 1767-1773
    CrossrefPubMedGoogle Scholar
  • 10 Iverson GM, Victoria EJ, Marquis DM. Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci U S A 1998; 95 (26) 15542-15546
    CrossrefPubMedGoogle Scholar
  • 11 de Laat B, de Groot PG. Autoantibodies directed against domain I of beta2-glycoprotein I. Curr Rheumatol Rep 2011; 13 (01) 70-76
    CrossrefPubMedGoogle Scholar
  • 12 Reddel SW, Wang YX, Sheng YH, Krilis SA. Epitope studies with anti-β 2-glycoprotein I antibodies from autoantibody and immunized sources. J Autoimmun 2000; 15 (02) 91-96
    CrossrefPubMedGoogle Scholar
  • 13 Pericleous C, Ferreira I, Borghi O. , et al. Measuring IgA anti-β2-glycoprotein I and IgG/IgA anti-domain I antibodies adds value to current serological assays for the antiphospholipid syndrome. PLoS One 2016; 11 (06) e0156407
    Google Scholar
  • 14 Ioannou Y, Romay-Penabad Z, Pericleous C. , et al. In vivo inhibition of antiphospholipid antibody-induced pathogenicity utilizing the antigenic target peptide domain I of beta2-glycoprotein I: proof of concept. J Thromb Haemost 2009; 7 (05) 833-842
    CrossrefPubMedGoogle Scholar
  • 15 Agostinis C, Durigutto P, Sblattero D. , et al. A noncomplement-fixing antibody to β2 glycoprotein I as a novel therapy for antiphospholipid syndrome. Blood 2014; 123 (22) 3478-3487
    CrossrefPubMedGoogle Scholar
  • 16 Sciascia S, Baldovino S, Schreiber K. , et al. Thrombotic risk assessment in antiphospholipid syndrome: the role of new antibody specificities and thrombin generation assay. Clin Mol Allergy 2016; 14 (01) 6
    CrossrefPubMedGoogle Scholar
  • 17 Ramagopalan SV, Wotton CJ, Handel AE, Yeates D, Goldacre MJ. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study. BMC Med 2011; 9 (01) 1
    CrossrefPubMedGoogle Scholar
  • 18 PRISMA 2009 checklist. Available at: http://prisma-statement.org/documents/PRISMA%202009%20checklist.pdf . Accessed: December 2016
    PubMed
  • 19 Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp . Accessed: December 2016
    PubMedGoogle Scholar
  • 20 Andreoli L, Nalli C, Motta M. , et al. Anti-β2-glycoprotein I IgG antibodies from 1-year-old healthy children born to mothers with systemic autoimmune diseases preferentially target domain 4/5: might it be the reason for their ‘innocent’ profile?. Ann Rheum Dis 2011; 70 (02) 380-383
    CrossrefPubMedGoogle Scholar
  • 21 Müller-Calleja N, Rossmann H, Müller C. , et al. Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression. Thromb Haemost 2016; 116 (01) 115-123
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 22 Pengo V, Ruffatti A, Tonello M. , et al. Antiphospholipid syndrome: antibodies to Domain 1 of β2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 2015; 13 (05) 782-787
    CrossrefPubMedGoogle Scholar
  • 23 Willis R, Pierangeli SS. Anti-β2-glycoprotein I antibodies. Ann N Y Acad Sci 2013; 1285 (01) 44-58
    CrossrefPubMedGoogle Scholar
  • 24 Despierres L, Beziane A, Kaplanski G. , et al. Contribution of anti-β2glycoprotein I IgA antibodies to the diagnosis of anti-phospholipid syndrome: potential interest of target domains to discriminate thrombotic and non-thrombotic patients. Rheumatology (Oxford) 2014; 53 (07) 1215-1218
    CrossrefPubMedGoogle Scholar
  • 25 Andreoli L, Nalli C, Borghi MO, Pregnolato F, Grossi C, Zangola A. , et al. Domain I is the main specificity of anti-beta2 GPI in systemic autoimmune diseases. Arthritis Rheum 2013; 65: S4
    CrossrefPubMedGoogle Scholar
  • 26 Zohoury N, Khamashta MA, Atsumi T, Musial J, Watanabe T, Papp M. , et al. Autoantibodies targeting domain 1 of beta 2 glycoprotein I as promising marker in the diagnosis and risk stratification of the antiphospholipid syndrome. Arthritis Rheum 2013; S4: 10
    PubMedGoogle Scholar
  • 27 de Laat B, Wu XX, van Lummel M, Derksen RH, de Groot PG, Rand JH. Correlation between antiphospholipid antibodies that recognize domain I of beta2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5. Blood 2007; 109 (04) 1490-1494
    CrossrefPubMedGoogle Scholar
  • 28 Manukyan D, Rossmann H, Schulz A. , et al. Distribution of antiphospholipid antibodies in a large population-based German cohort. Clin Chem Lab Med 2016; 54 (10) 1663-1670
    CrossrefPubMedGoogle Scholar
  • 29 Roggenbuck D, Borghi MO, Somma V. , et al. Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers. Arthritis Res Ther 2016; 18 (01) 111
    CrossrefPubMedGoogle Scholar
  • 30 Rodríguez-García V, Ioannou Y, Fernández-Nebro A, Isenberg DA, Giles IP. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology (Oxford) 2015; 54 (11) 2042-2050
    CrossrefPubMedGoogle Scholar
  • 31 Meneghel L, Ruffatti A, Gavasso S. , et al. Detection of IgG anti-domain I beta2 glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome. Clin Chim Acta 2015; 446: 201-205
    CrossrefPubMedGoogle Scholar
  • 32 de Laat B, Derksen RHWM, 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 (04) 1540-1545
    CrossrefPubMedGoogle Scholar
  • 33 Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003; 102 (08) 2717-2723
    CrossrefPubMedGoogle Scholar
  • 34 Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101 (05) 1827-1832
    CrossrefPubMedGoogle Scholar
  • 35 Zhang S, Wu Z, Chen S. , et al. Evaluation of the diagnostic potential of antibodies to beta2-glycoprotein 1 domain 1 in Chinese patients with antiphospholipid syndrome. Sci Rep 2016; 6 (01) 23839
    CrossrefPubMedGoogle Scholar
  • 36 Agmon-levin N, Seguro L, Rosa C. , et al. Anti-β2GPI-D1 antibodies are a marker of APS severity. Arthritis Rheumatol 2013; 65 (10) S4
    CrossrefPubMedGoogle Scholar
  • 37 Wahezi DM, Ilowite NT, Wu XX. , et al; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators. Annexin A5 anticoagulant activity in children with systemic lupus erythematosus and the association with antibodies to domain I of β2-glycoprotein I. Lupus 2013; 22 (07) 702-711
    CrossrefPubMedGoogle Scholar
  • 38 Mahler M, Albesa R, Zohoury N. , et al. Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome. Lupus 2016; 25 (08) 911-916
    CrossrefPubMedGoogle Scholar
  • 39 Cieśla M, Wypasek E, Undas A. 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. Adv Clin Exp Med 2014; 23 (05) 729-733
    CrossrefPubMedGoogle Scholar
  • 40 Mondejar R, González-Rodríguez C, Toyos-Sáenz de Miera FJ. , et al. Role of antiphospholipid score and anti-β2-glycoprotein I Domain I autoantibodies in the diagnosis of antiphospholipid syndrome. Clin Chim Acta 2014; 431: 174-178
    CrossrefPubMedGoogle Scholar
  • 41 Hunt BJ, Wu X-X, de Laat B, Arslan AA, Stuart-Smith S, Rand JH. Resistance to annexin A5 anticoagulant activity in women with histories for obstetric antiphospholipid syndrome. Am J Obstet Gynecol 2011; 205 (05) 485.e17-485.e23
    CrossrefPubMedGoogle Scholar
  • 42 Andreoli L, Chighizola CB, Nalli C. , et al. Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against β2 -glycoprotein i domain 1 and domain 4/5: ratio of anti-domain 1 to anti-domain 4/5 as a useful new biomarker for antiphospholipid syndrome. Arthritis Rheumatol 2015; 67 (08) 2196-2204
    CrossrefPubMedGoogle Scholar
  • 43 De Craemer A-S, Devreese KM. Role of anti-domain 1-ß2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome: reply. J Thromb Haemost 2016; 14 (10) 2078-2080
    CrossrefPubMedGoogle Scholar
  • 44 Cousins L, Pericleous C, Khamashta M. , et al. Antibodies to domain I of β-2-glycoprotein I and IgA antiphospholipid antibodies in patients with ‘seronegative’ antiphospholipid syndrome. Ann Rheum Dis 2015; 74 (01) 317-319
    CrossrefPubMedGoogle Scholar
  • 45 Chighizola CB, Gerosa M, Meroni PL. New tests to detect antiphospholipid antibodies: anti-domain I beta-2-glycoprotein-I antibodies. Curr Rheumatol Rep 2014; 16 (02) 402
    CrossrefPubMedGoogle Scholar
  • 46 Willis R, Grossi C, Orietta Borghi M. , et al. International standards for IgG and IgM anti-β2glycoprotein antibody measurement. Lupus 2014; 23 (12) 1317-1319
    CrossrefPubMedGoogle Scholar
  • 47 Conrad K, Andrade LE, Chan EK, Mahler M, Meroni PL, Pruijn GJ. , et al. From autoantibody research to standardized diagnostic assays in the management of human diseases - . Report of the 12th Dresden Symposium on Autoantibodies. Lupus 2016; 25 (08) 787-796
    CrossrefPubMedGoogle Scholar