Cecilia Nalli and Valentina Somma shared first authorship.
Dirk Roggenbuck and Angela Tincani shared senior authorship.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Anti-phospholipid antibodies (aPL) analyzed by line immunoassay (LIA) can recognize beta2-glycoprotein I (β2GPI) domain 1 (D1) epitopes depending on β2GPI binding to distinct phospholipids. The aPL LIA was compared with consensus ELISA to investigate whether both techniques can discriminate anti-phospholipid syndrome (APS) patients from aPL-positive, systemic autoimmune rheumatic diseases (SARD) patients without clinical symptoms of APS and controls.
Thirty-four APS patients (14 arterial/venous thrombosis, 16 pregnancy morbidity, and 4 both), 41 patients with SARD lacking clinical APS criteria but demonstrating positivity for anti-β2GPI (aβ2GPI) IgG, and 20 healthy subjects (HS) were tested for aPL to cardiolipin (aCL), phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol (aPG), phosphatidylinositol, phosphatidylserine, β2GPI, prothrombin, and annexin V by LIA. Samples were also tested for aCL, aβ2GPI, aβ2GPI-domain 1 (aD1), and aβ2GPI-domains 4–5 (aD4–5) by ELISA and for lupus anti-coagulant.
Comparison of LIA with ELISA revealed a good agreement for the consensus criteria aPL aβ2GPI and aCL IgG (kappa = 0.69, 0.68, respectively) and a moderate agreement for IgM (kappa = 0.52, 0.49, respectively). Regarding ELISA, aD1/aD4–5 demonstrated the best performance of differentiating APS from asymptomatic SARD [area under the curve (AUC): 0.76]. aPG IgG had the best performance by LIA (AUC: 0.72) not significantly different from aD1/aD4–5. There was a good agreement for aPG IgG with aD1/aD4–5 (kappa = 0.71).
aD1/aD4–5 (ELISA) and aPG IgG (LIA) differentiate APS from SARD patients. PG appears to interact with β2GPI of APS patients and exposes D1 thereof for disease-specific aPL binding in LIA.
Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA (2010) Antiphospholipid syndrome. Lancet 376:1498–1509 CrossRef
Meroni PL, Borghi MO, Raschi E, Tedesco F (2011) Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol 7:330–339 CrossRef
Asherson RA, Cervera R, DeGroot PG, Erkan D, Boffa MC, Piette JC, Kamashta MA, Shoenfeld Y (2003) Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 12:530–534 CrossRef
Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, deGroot P, Lakos G, Lambert M, Meroni P, Ortel TL, Petri M, Rahman A, Roubey R, Sciascia S, Snyder M, Tebo AE, Tincani A, Willis R (2014) 14th International Congress on Antiphospholipid Antibodies Task Force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev 13:917–930 CrossRef
Tebo AE, Willis R, Jaskowski TD, Guerra M, Pierangeli SS, Salmon J, Petri M, Branch DW (2016) Clinical significance and correlations between anti-beta2 glycoprotein I IgA assays in antiphospholipid syndrome and/or systemic lupus erythematosus. Clin Chim Acta 460:107–113 CrossRef
Nalli C, Piantoni S, Andreoli L, Motta M, Tincani A (2012) Antiphospholipid syndrome and antiphospholipid antibodies in children: the two sides of the coin. Isr Med Assoc J 14:310–312 PubMed
Andreoli L, Nalli C, Motta M, Norman GL, Shums Z, Encabo S, Binder WL, Nuzzo M, Frassi M, Lojacono A, Avcin T, Meroni PL, Tincani A (2011) Anti-beta(2)-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 70:380–383 CrossRef
deLaat B, Derksen RH, Urbanus RT, DeGroot PG (2005) 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 105:1540–1545 CrossRef
Andreoli L, Chighizola CB, Nalli C, Gerosa M, Borghi MO, Pregnolato F, Grossi C, Zanola A, Allegri F, Norman GL, Mahler M, Meroni PL, Tincani A (2015) Clinical characterization of antiphospholipid syndrome by detection of IgG antibodies against beta2-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 CrossRef
Mattia E, Ruffatti A, Meneghel L, Tonello M, Faggian D, Hoxha A, Fredrigo M, Punzi L, Plebani M (2015) A contribution to detection of anticardiolipin and anti-beta2glycoprotein I antibodies: comparison between a home-made ELISA and a fluorescence enzyme immunoassay. Clin Chim Acta 446:93–96 CrossRef
Mahler M, Norman GL, Meroni PL, Khamashta M (2012) Autoantibodies to domain 1 of beta 2 glycoprotein 1: a promising candidate biomarker for risk management in antiphospholipid syndrome. Autoimmun Rev 12:313–317 CrossRef
Fickentscher C, Magorivska I, Janko C, Biermann M, Bilyy R, Nalli C, Tincani A, Medeghini V, Meini A, Nimmerjahn F, Schett G, Muñoz LE, Andreoli L, Herrmann M (2015) The pathogenicity of anti-β2GP1-IgG autoantibodies depends on Fc glycosylation. J Immunol Res 2015:638129 CrossRef
Mahler M, Albesa R, Zohoury N, Bertolaccini ML, Ateka-Barrutia O, Rodriguez-Garcia JL, Norman GL, Khamashta M (2016) 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 25:911–916 CrossRef
Meneghel L, Ruffatti A, Gavasso S, Meneghel L, Tonello M, Salvan E, Pengo V, Punzi V (2015) Detection of IgG anti-domain I beta2 Glycoprotein I antibodies by chemiluminescence immunoassay in primary antiphospholipid syndrome. Clin Chim Acta 446:201–205 CrossRef
Erkan D, Lockshin MD (2012) APS ACTION-antiphospholipid syndrome alliance for clinical trials and international networking. Lupus 21:695–698 CrossRef
Roggenbuck D, Borghi MO, Somma V, Büttner T, Schierack P, Hanack K, Grossi C, Bodio C, Macor P, von Landenberg P, Boccellato F, Mahler M, Meroni PL (2016) Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers. Arthritis Res Ther 18:111 CrossRef
Meroni PL, Biggioggero M, Pierangeli SS, Sheldon J, Zegers I, Borghi MO (2014) Standardization of autoantibody testing: a paradigm for serology in rheumatic diseases. Nat Rev Rheumatol 10:35–43 CrossRef
Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S (2005) Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 93:1147–1152 CrossRef
Roggenbuck D, Egerer K, von Landenberg P, Hiemann R, Feist E, Burmester GR, Dörner T (2012) Antiphospholipid antibody profiling—time for a new technical approach. Autoimmun Rev 11:821–826 CrossRef
Hoxha A, Ruffatti A, Mattia E, Meneghel L, Tonello M, Salvan E, Pengo V, Punzi L (2015) Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome. Clin Chem Lab Med 53:1265–1270 CrossRef
Egerer K, Roggenbuck D, Buettner T, Lehmann B, Kohn A, von Landenberg P, Hiemann R, Feist E, Burmester GR, Dörner T (2011) Single-step autoantibody profiling in antiphospholipid syndrome using a multi-line dot assay. Arthritis Res Ther 13:R118 CrossRef
Roggenbuck D, Egerer K, Feist E, Burmester GR, Dorner T (2012) Antiphospholipid antibody profiling—association with the clinical phenotype in APS? Arthritis Rheum 64:2807–2808 CrossRef
Roggenbuck D, Somma V, Schierack P, Borghi MO, Meroni PL (2014) Autoantibody profiling in APS. Lupus 23:1262–1264 CrossRef
Pengo V (2012) ISTH guidelines on lupus anticoagulant testing. Thromb Res 130(Suppl 1):S76–S77 CrossRef
Devreese KM, Pierangeli SS, de Laat Tripodi A, Atsumi T, Ortel TL (2014) Testing for antiphospholipid antibodies with solid phase assays: guidance from the SSC of the ISTH. J Thromb Haemost 12:792–795 CrossRef
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 (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306 CrossRef
Meroni PL (2016) Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools. Lupus 25:905–910 CrossRef
Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E, Denas G, Padayattil Jose S (2015) Antiphospholipid syndrome: antibodies to Domain 1 of beta2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 13:782–787 CrossRef
Pengo V, Banzato A, Denas G, Jose SP, Bison E, Hoxha A, Ruffatti A (2013) Correct laboratory approach to APS diagnosis and monitoring. Autoimmun Rev 12:832–834 CrossRef
Schoenherr G, Roggenbuck D, Seifert M, Jahn S, Porstmann T (1996) Technical problems arising from the use of the immunoblot for determination of the reactivity of natural antibodies with different lipopolysaccharides (LPS). J Immunol Methods 190:185–188 CrossRef
Seifert M, Schoenherr G, Roggenbuck D, Marx U, von Baehr R (1996) Generation and characterization of a human monoclonal IgM antibody that recognizes a conserved epitope shared by lipopolysaccharides of different gram-negative bacteria. Hybridoma 15:191–198 CrossRef
Conrad K, Schneider H, Ziemssen T, Talaska T, Reinhold D, Humbel RL, Roggenbuck D (2007) A new line immunoassay for the multiparametric detection of antiganglioside autoantibodies in patients with autoimmune peripheral neuropathies. Ann N Y Acad Sci 1109:256–264 CrossRef
Sathappa M, Alder NN (2016) The ionization properties of cardiolipin and its variants in model bilayers. Biochim Biophys Acta 1858:1362–1372 CrossRef
Chighizola CB, Ubiali T, Meroni PL (2015) Treatment of thrombotic antiphospholipid syndrome: the rationale of current management—an insight into future approaches. J Immunol Res 2015:951424 CrossRef
- Anti-phospholipid IgG antibodies detected by line immunoassay differentiate patients with anti-phospholipid syndrome and other autoimmune diseases
- Springer International Publishing
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II