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Anti-beta-2-glycoprotein I domain 1 identifies antiphospholipid antibodies-related injuries in patients with concomitant lupus nephritis

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Abstract

Background

In this study we aimed to evaluate the usefulness of domain profiling of Beta-2-glycoprotein I(β2GPI)-Domain-1 (D1) antibodies in relation to antiphospholipid antibodies (aPL)-related nephropathy (aPL-N) in patients with biopsy-proven lupus nephritis (LN).

Methods

Of 124 consecutive patients (96 women, mean age 45.5 ± 12.3 years, mean disease duration 14.7 ± 9.6 years) fulfilling the 1982 criteria for systemic lupus erythematosus (SLE), we identified 39 patients (mean age 39.84 ± 8.6 years, mean disease duration 11.3 ± 7.7 years) with the following characteristics: (a) biopsy-proven LN; (b) no previous diagnosis of antiphospholipid syndrome (APS) according to the current classification criteria.

Results

Patients with both LN and aPL-N had higher median aβ2GPI-D1 antibody titres (220.1 CU, 25–75th IQ 29.1–334.2) as compared those with LN alone (46.5 CU, 25–75th IQ 12.5–75.1) (p = 0.0087). Median aβ2GPI-D1 antibody titres were higher in patients with acute thrombotic microangiopathy (aTMA) (N = 7) (250.1 CU, 25–75th IQ 61.2–334.2) vs. with LN alone (46.5 CU, 25–75th IQ 12.5–75.1 CU) (p = 0.0009). Having a Global Antiphospholipid Syndrome Score > 10 confers an increased probability of having acute features of aTMA (OR 6.25, 95%CI 1.2–31.8). As compared to other aPL, aβ2GPI-D1 antibodies have the best diagnostic accuracy for aTMA as evaluated by performances in Area Under the Curves in a ROC analysis.

Conclusions

aβ2GPI-D1 antibodies detection might provide a second-line assay to be performed in aβ2GPI positive patients with LN, allowing more accurate stratification of the renal vascular involvement risk, thus potentially leading to a more tailored management.

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References

  1. Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x

    Article  CAS  PubMed  Google Scholar 

  2. Meroni PL, Borghi MO, Raschi E, Tedesco F (2011) Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol 7:330–339. https://doi.org/10.1038/nrrheum.2011.52

    Article  CAS  PubMed  Google Scholar 

  3. Shoenfeld Y, Krause I, Kvapil F et al (2003) Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome. J Clin Immunol 23:377–383

    Article  CAS  Google Scholar 

  4. Chighizola CB, Gerosa M, Meroni PL (2014) New tests to detect antiphospholipid antibodies: Anti-domain i beta-2-glycoprotein-I antibodies. Curr Rheumatol Rep 16:1–9. https://doi.org/10.1007/s11926-013-0402-7

    Article  CAS  Google Scholar 

  5. Iverson GM, Victoria EJ, Marquis DM (1998) Anti-beta2 glycoprotein I (beta2GPI) autoantibodies recognize an epitope on the first domain of beta2GPI. Proc Natl Acad Sci USA 95:15542–15546

    Article  CAS  Google Scholar 

  6. McNeeley PA, Dlott JS, Furie RA et al (2001) β2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of β2-glycoprotein I. Thromb Haemost 86:590–595. https://doi.org/10.1055/s-0037-1616091

    Article  CAS  PubMed  Google Scholar 

  7. Iverson GM, Reddel S, Victoria EJ et al (2002) Use of single point mutations in domain I of beta 2-glycoprotein I to determine fine antigenic specificity of antiphospholipid autoantibodies. J Immunol 169:7097–7103

    Article  CAS  Google Scholar 

  8. Ioannou Y, Pericleous C, Giles I et al (2007) Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43. Arthritis Rheum 56:280–290. https://doi.org/10.1002/art.22306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. De Laat B, Van Berkel M, Urbanus RT et al (2011) Immune responses against domain I of ß2-glycoprotein I are driven by conformational changes: domain I of ß2-glycoprotein I harbors a cryptic immunogenic epitope. Arthritis Rheum 63:3960–3968. https://doi.org/10.1002/art.30633

    Article  CAS  PubMed  Google Scholar 

  10. Pengo V, Ruffatti A, Legnani C et al (2011) Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood 118:4714–4718. https://doi.org/10.1182/blood-2011-03-340232

    Article  CAS  PubMed  Google Scholar 

  11. Chighizola CB, Pregnolato F, Andreoli L et al (2018) Beyond thrombosis: Anti-β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome. J Autoimmun 90:76–83. https://doi.org/10.1016/j.jaut.2018.02.002

    Article  CAS  PubMed  Google Scholar 

  12. Andreoli L, Chighizola CB, Nalli C et al (2015) Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against antiBeta2-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 67:2196–2204. https://doi.org/10.1002/art.39187

    Article  CAS  PubMed  Google Scholar 

  13. Andreoli L, Nalli C, Borghi MO, Pregnolato F, Grossi C, Zangola A, Allegri F, Gerosa M, Mahler M, Norman G, Meroni P, and Tincani A (2013) Domain 1 is the main specificity of anti-b2glycoprotein I antibodies in systemic autoimmune diseases. Arthritis Rheum 65:S4

    Article  Google Scholar 

  14. Sciascia S, Amigo M-C, Roccatello D, Khamashta M (2017) Diagnosing antiphospholipid syndrome: “extra-criteria” manifestations and technical advances. Nat Rev Rheumatol. https://doi.org/10.1038/nrrheum.2017.124

    Article  PubMed  Google Scholar 

  15. Pattanashetti N, Anakutti H, Ramachandran R et al (2017) Effect of thrombotic microangiopathy on clinical outcomes in Indian patients with lupus nephritis. Kidney Int Rep 2:844–849. https://doi.org/10.1016/j.ekir.2017.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sciascia S, Yazdany J, Dall’Era M et al (2018) Anticoagulation in patients with concomitant lupus nephritis and thrombotic microangiopathy: a multicentre cohort study. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2018-214559

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277

    Article  CAS  Google Scholar 

  18. Weening JJ, D’Agati VD, Schwartz MM et al (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15:241–250. https://doi.org/10.1097/01.ASN.0000108969.21691.5D

    Article  PubMed  Google Scholar 

  19. Sciascia S, Cuadrado MJ, Khamashta M, Roccatello D (2014) Renal involvement in antiphospholipid syndrome. Nat Rev Nephrol. https://doi.org/10.1038/nrneph.2014.38

    Article  PubMed  Google Scholar 

  20. Pengo V, Tripodi A, Reber G et al (2009) Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 7:1737–1740. https://doi.org/10.1111/j.1538-7836.2009.03555.x

    Article  CAS  PubMed  Google Scholar 

  21. Pengo V, Ruffatti A, Tonello M et al (2015) Antiphospholipid syndrome: antibodies to domain 1 of β2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 13:782–787. https://doi.org/10.1111/jth.12865

    Article  CAS  PubMed  Google Scholar 

  22. Sciascia S, Sanna G, Murru V et al (2013) GAPSS: the global anti-phospholipid syndrome score. Rheumatology (Oxford) 52:1397–1403. https://doi.org/10.1093/rheumatology/kes388

    Article  Google Scholar 

  23. Radin M, Cecchi I, Roccatello D et al (2017) Prevalence and thrombotic risk assessment of anti-β2 glycoprotein I domain I antibodies: a systematic review. Semin Thromb Hemost. https://doi.org/10.1055/s-0037-1603936

    Article  PubMed  Google Scholar 

  24. Song D, Wu L, Wang F et al (2013) The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther 15:R12. https://doi.org/10.1186/ar4142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Meroni PL (2016) Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools. Lupus 25:905–910. https://doi.org/10.1177/0961203316641772

    Article  CAS  PubMed  Google Scholar 

  26. Agostinis C, Biffi S, Garrovo C et al (2011) In vivo distribution of β2 glycoprotein I under various pathophysiologic conditions. Blood 118:4231–4238. https://doi.org/10.1182/blood-2011-01-333617

    Article  CAS  PubMed  Google Scholar 

  27. Meroni PL, Macor P, Durigutto P et al (2016) Complement activation in antiphospholipid syndrome and its inhibition to prevent rethrombosis after arterial surgery. Blood 127:365–367. https://doi.org/10.1182/blood-2015-09-672139

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

Authors

Contributions

SS, MR, DRoc: research idea and study design; DRoc, LB, DRos, RF, ADM: data acquisition; SS, MR, IC, ER, DRoc: data analysis/interpretation; MR, SS, PM, SB: statistical analysis; DRoc, SS supervision or mentorship. SS: takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

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Correspondence to Savino Sciascia.

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The study was conducted according to the declaration of Helsinki and informed consent was given to all patients that participated in the study.

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Sciascia, S., Radin, M., Cecchi, I. et al. Anti-beta-2-glycoprotein I domain 1 identifies antiphospholipid antibodies-related injuries in patients with concomitant lupus nephritis. J Nephrol 33, 757–762 (2020). https://doi.org/10.1007/s40620-019-00698-9

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