Semin Thromb Hemost 2022; 48(02): 132-144
DOI: 10.1055/s-0041-1730357
Review Article

Laboratory Approaches to Test the Function of Antiphospholipid Antibodies

Gábor Szabó
1   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2   Thrombosis, Haemostasis and Vascular Biology Programme, Kálmán Laki Doctoral School, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Péter Antal-Szalmás
1   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Adrienne Kerényi
1   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
3   Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary
Krisztina Pénzes
4   Division of Medical Laboratory Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Bálint Bécsi
5   Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
János Kappelmayer
1   Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
› Author Affiliations
Funding This work was supported by Hungarian Scientific Research Fund (OTKA_K_16 120725), and Economic Development and Innovation Operational Programme (GINOP-2.3.3–15-2016–00020).


Antiphospholipid syndrome (APS) is a systemic autoimmune disorder caused by the presence of aPLs (antiphospholipid antibodies, i.e., anti-β2-glycoprotein I and anti-cardiolipin). Everyday practice in terms of laboratory diagnostics of APS includes determination of aPLs and well-known functional assays assessing for lupus anticoagulant (LA), in turn using various tests. According to recent guidelines, the recommended method for LA identification or exclusion is based on the Russell Viper Venom test and a sensitive activated partial thromboplastin time assay. Despite the fact that LA can be quantified in laboratory practice in this way, LA is still used as a binary parameter that is just one of the risk factors of thrombosis in APS. As of today, there are no other functional assays to routinely assess the risk of thrombosis in APS. It is well-known that APS patients display a wide range of clinical outcomes although they may express very similar laboratory findings. One way to solve this dilemma, could be if antibodies could be further delineated using more advanced functional tests. Therefore, we review the diagnostic approaches to test the function of aPLs. We further discuss how thrombin generation assays, and rotational thromboelastometry tests can be influenced by LA, and how experimental methods, such as flow cytometric platelet activation, surface plasmon resonance, or nano differential scanning fluorimetry can bring us closer to the puzzling interaction of aPLs with platelets as well as with their soluble protein ligand. These novel approaches may eventually enable better characterization of aPL, and also provide a better linkage to APS pathophysiology.

Publication History

Article published online:
14 July 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing. Int J Celiac Disease 2015; 3 (04) 151-155
  • 2 Suurmond J, Diamond B. Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity. J Clin Invest 2015; 125 (06) 2194-2202
  • 3 Neiman M, Hellström C, Just D. et al. Individual and stable autoantibody repertoires in healthy individuals. Autoimmunity 2019; 52 (01) 1-11
  • 4 Cavazzana I, Andreoli L, Limper M, Franceschini F, Tincani A. Update on antiphospholipid syndrome: ten topics in 2017. Curr Rheumatol Rep 2018; 20 (03) 15
  • 5 Agmon-Levin N, Damoiseaux J, Kallenberg C. et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis 2014; 73 (01) 17-23
  • 6 DE Moerloose P, Reber G, Musial J, Arnout J. Analytical and clinical performance of a new, automated assay panel for the diagnosis of antiphospholipid syndrome. J Thromb Haemost 2010; 8 (07) 1540-1546
  • 7 Persijn L, Decavele AS, Schouwers S, Devreese K. Evaluation of a new set of automated chemiluminescense assays for anticardiolipin and anti-beta2-glycoprotein I antibodies in the laboratory diagnosis of the antiphospholipid syndrome. Thromb Res 2011; 128 (06) 565-569
  • 8 Villalta D, Alessio MG, Tampoia M. et al. Accuracy of the first fully automated method for anti-cardiolipin and anti-beta2 glycoprotein I antibody detection for the diagnosis of antiphospholipid syndrome. Ann N Y Acad Sci 2009; 1173: 21-27
  • 9 Vignali DA. Multiplexed particle-based flow cytometric assays. J Immunol Methods 2000; 243 (1-2): 243-255
  • 10 Graham H, Chandler DJ, Dunbar SA. The genesis and evolution of bead-based multiplexing. Methods 2019; 158: 2-11
  • 11 Staudt N, Müller-Sienerth N, Wright GJ. Development of an antigen microarray for high throughput monoclonal antibody selection. Biochem Biophys Res Commun 2014; 445 (04) 785-790
  • 12 Hueber W, Kidd BA, Tomooka BH. et al. Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis Rheum 2005; 52 (09) 2645-2655
  • 13 Vasilev VV, Noe R, Dragon-Durey MA. et al. Functional characterization of autoantibodies against complement component C3 in patients with lupus nephritis. J Biol Chem 2015; 290 (42) 25343-25355
  • 14 Prechl J, Papp K, Hérincs Z. et al. Serological and genetic evidence for altered complement system functionality in systemic lupus erythematosus: findings of the GAPAID consortium. PLoS One 2016; 11 (03) e0150685
  • 15 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
  • 16 Galli M, Comfurius P, Maassen C. et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335 (8705): 1544-1547
  • 17 Jy W, Tiede M, Bidot CJ. et al. Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies. Thromb Res 2007; 121 (03) 319-325
  • 18 Membre A, Wahl D, Latger-Cannard V. et al. The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies. Haematologica 2008; 93 (04) 566-573
  • 19 Pennings MT, Derksen RH, van Lummel M. et al. Platelet adhesion to dimeric beta-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ibalpha and apolipoprotein E receptor 2′. J Thromb Haemost 2007; 5 (02) 369-377
  • 20 Clemens N, Frauenknecht K, Katzav A, Sommer C, von Landenberg P. In vitro effects of antiphospholipid syndrome-IgG fractions and human monoclonal antiphospholipid IgG antibody on human umbilical vein endothelial cells and monocytes. Ann N Y Acad Sci 2009; 1173: 805-813
  • 21 Cañas F, Simonin L, Couturaud F, Renaudineau Y. Annexin A2 autoantibodies in thrombosis and autoimmune diseases. Thromb Res 2015; 135 (02) 226-230
  • 22 Romay-Penabad Z, Montiel-Manzano MG, Shilagard T. et al. Annexin A2 is involved in antiphospholipid antibody-mediated pathogenic effects in vitro and in vivo. Blood 2009; 114 (14) 3074-3083
  • 23 Motoki Y, Nojima J, Yanagihara M. et al. Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells. Thromb Res 2012; 130 (04) 667-673
  • 24 Cifù A, Domenis R, Pistis C, Curcio F, Fabris M. Anti-β2-glycoprotein I and anti-phosphatidylserine/prothrombin antibodies exert similar pro-thrombotic effects in peripheral blood monocytes and endothelial cells. Auto Immun Highlights 2019; 10 (01) 3
  • 25 Manukyan G, Martirosyan A, Slavik L. et al. Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro. Auto Immun Highlights 2020; 11 (01) 5
  • 26 Nojima J, Masuda Y, Iwatani Y. et al. Tissue factor expression on monocytes induced by anti-phospholipid antibodies as a strong risk factor for thromboembolic complications in SLE patients. Biochem Biophys Res Commun 2008; 365 (01) 195-200
  • 27 Galli M, Willems GM, Rosing J. et al. Anti-prothrombin IgG from patients with anti-phospholipid antibodies inhibits the inactivation of factor Va by activated protein C. Br J Haematol 2005; 129 (02) 240-247
  • 28 Liestøl S, Sandset PM, Jacobsen EM, Mowinckel MC, Wisløff F. Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants. Br J Haematol 2007; 136 (01) 131-137
  • 29 Rand JH, Wu XX, Quinn AS, Taatjes DJ. Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome. Lupus 2008; 17 (10) 922-930
  • 30 McNally T, Mackie IJ, Isenberg DA, Machin SJ. beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich lipoproteins: the effect of antibodies from plasma of patients with antiphospholipid syndrome. Thromb Haemost 1996; 76 (02) 220-225
  • 31 Shi T, Iverson GM, Qi JC. et al. Beta 2-glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: loss of inhibition by clipped beta 2-glycoprotein I. Proc Natl Acad Sci U S A 2004; 101 (11) 3939-3944
  • 32 Gropp K, Weber N, Reuter M. et al. β2-glycoprotein I, the major target in antiphospholipid syndrome, is a special human complement regulator. Blood 2011; 118 (10) 2774-2783
  • 33 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
  • 34 Tortosa C, Cabrera-Marante O, Serrano M. et al. Incidence of thromboembolic events in asymptomatic carriers of IgA anti ß2 glycoprotein-I antibodies. PLoS One 2017; 12 (07) e0178889
  • 35 Pérez D, Tincani A, Serrano M, Shoenfeld Y, Serrano A. Antiphospholipid syndrome and IgA anti-beta2-glycoprotein I antibodies: when Cinderella becomes a princess. Lupus 2018; 27 (02) 177-178
  • 36 Chayoua W, Kelchtermans H, Gris JC. et al. The (non-)sense of detecting anti-cardiolipin and anti-β2glycoprotein I IgM antibodies in the antiphospholipid syndrome. J Thromb Haemost 2020; 18 (01) 169-179
  • 37 Devreese KMJ. Testing for antiphospholipid antibodies: Advances and best practices. Int J Lab Hematol 2020; 42 (Suppl. 01) 49-58
  • 38 Demir S, Li J, Magder LS, Petri M. Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus. Rheumatology (Oxford) 2020; keaa857
  • 39 Tebo AE. Laboratory evaluation of antiphospholipid syndrome: an update on autoantibody testing. Clin Lab Med 2019; 39 (04) 553-565
  • 40 Willis R, Lakos G, Harris EN. Standardization of antiphospholipid antibody testing—historical perspectives and ongoing initiatives. Semin Thromb Hemost 2014; 40 (02) 172-177
  • 41 Pengo V, Tripodi A, Reber G. et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 7 (10) 1737-1740
  • 42 Devreese KMJ, de Groot PG, de Laat B. et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost 2020; 18 (11) 2828-2839
  • 43 Agar C, van Os GM, Mörgelin M. et al. Beta2-glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood 2010; 116 (08) 1336-1343
  • 44 Miyakis S, Giannakopoulos B, Krilis SA. Beta 2 glycoprotein I--function in health and disease. Thromb Res 2004; 114 (5-6): 335-346
  • 45 De Craemer AS, Musial J, Devreese KM. Role of anti-domain 1-β2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome. J Thromb Haemost 2016; 14 (09) 1779-1787
  • 46 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 (04) 1540-1545
  • 47 Yin ET, Gaston LW. Purification and kinetic studies on a circulating anticoagulant in a suspected case of lupus erythematosus. Thromb Diath Haemorrh 1965; 14 (1-2): 88-115
  • 48 Smith LJ. Laboratory diagnosis of the lupus anticoagulant. American Society for Clinical Laboratory Science 2017; 30 (01) 7-14
  • 49 Tripodi A, Cohen H, Devreese KMJ. Lupus anticoagulant detection in anticoagulated patients. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2020; 18 (07) 1569-1575
  • 50 Schouwers SM, Delanghe JR, Devreese KM. Lupus Anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results?. Thromb Res 2010; 125 (01) 102-104
  • 51 Kershaw G, Suresh S, Orellana D, Nguy YM. Laboratory identification of lupus anticoagulants. Semin Thromb Hemost 2012; 38 (04) 375-384
  • 52 Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost 2012; 10 (11) 2338-2343
  • 53 Tokutake T, Ieko M, Naito S. et al. Magnesium-dependent activated partial thromboplastin time assay—simple method for lupus anticoagulant detection. Int J Lab Hematol 2020; 42 (01) 46-51
  • 54 Favaloro EJ. Coagulation mixing studies: utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests. Am J Hematol 2020; 95 (01) 117-128
  • 55 Favaloro EJ, Bonar R, Marsden K. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: Part II—lupus anticoagulant. Semin Thromb Hemost 2012; 38 (04) 404-411
  • 56 Keeling D, Mackie I, Moore GW, Greer IA, Greaves M. British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 2012; 157 (01) 47-58
  • 57 Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost 2014; 40 (02) 163-171
  • 58 CLSI. Laboratory Testing for the Lupus Anticoagulant; approved guideline. CLSI document H60-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2014
  • 59 Devreese KM. Antiphospholipid antibody testing and standardization. Int J Lab Hematol 2014; 36 (03) 352-363
  • 60 Asherson RA, Cervera R. Antiphospholipid antibodies and infections. Ann Rheum Dis 2003; 62 (05) 388-393
  • 61 Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005; 93 (06) 1147-1152
  • 62 Pengo V, Ruffatti A, Legnani C. et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood 2011; 118 (17) 4714-4718
  • 63 Pignatelli P, Ettorre E, Menichelli D, Pani A, Violi F, Pastori D. Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management. Haematologica 2020; 105 (03) 562-572
  • 64 Cattini MG, Bison E, Pontara E, Cheng C, Denas G, Pengo V. Tetra positive thrombotic antiphospholipid syndrome: major contribution of anti-phosphatidyl-serine/prothrombin antibodies to lupus anticoagulant activity. J Thromb Haemost 2020; 18 (05) 1124-1132
  • 65 Lippi G, Mattiuzzi C, Adcock D, Favaloro EJ. Oral anticoagulants around the world: an updated state-of-the art analysis. Ann Blood 2018; 3: 49
  • 66 Favaloro EJ, Mohammed S, Curnow J, Pasalic L. Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives. Pathology 2019; 51 (03) 292-300
  • 67 Bonar R, Favaloro EJ, Mohammed S. et al. The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology 2016; 48 (01) 60-71
  • 68 Favaloro EJ, Gilmore G, Arunachalam S, Mohammed S, Baker R. Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): a comparative study using DOAC Stop and andexanet alfa. Thromb Res 2019; 180: 10-19
  • 69 Favaloro EJ. The Russell viper venom time (RVVT) test for investigation of lupus anticoagulant (LA). Am J Hematol 2019; 94 (11) 1290-1296
  • 70 Exner T, Michalopoulos N, Pearce J, Xavier R, Ahuja M. Simple method for removing DOACs from plasma samples. Thromb Res 2018; 163: 117-122
  • 71 Monteyne T, De Kesel P, Devreese KMJ. Interference of DOAC stop and DOAC remove in the thrombin generation assay and coagulation assays. Thromb Res 2020; 192: 96-99
  • 72 Riva N, Vella K, Hickey K. et al. The effect of DOAC-Stop® on several oral and parenteral anticoagulants [abstract]. Res Pract Thromb Haemost 2020;4(Suppl 1)
  • 73 Jourdi G, Delrue M, Stepanian A. et al. Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving direct oral anticoagulants. Thromb Res 2019; 184: 86-91
  • 74 Lancé MD. A general review of major global coagulation assays: thrombelastography, thrombin generation test and clot waveform analysis. Thromb J 2015; 13: 1
  • 75 Kintigh J, Monagle P, Ignjatovic V. A review of commercially available thrombin generation assays. Res Pract Thromb Haemost 2017; 2 (01) 42-48
  • 76 Calzavarini S, Brodard J, Quarroz C. et al. Thrombin generation measurement using the ST Genesia Thrombin Generation System in a cohort of healthy adults: normal values and variability. Res Pract Thromb Haemost 2019; 3 (04) 758-768
  • 77 van Paridon PCS, Panova-Noeva M, van Oerle R. et al. Thrombin generation in cardiovascular disease and mortality—results from the Gutenberg Health Study. Haematologica 2020; 105 (09) 2327-2334
  • 78 Devreese K, Peerlinck K, Hoylaerts MF. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood 2010; 115 (04) 870-878
  • 79 Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clin Chem 2016; 62 (05) 699-707
  • 80 Szabó G, Debreceni IB, Tarr T, Soltész P, Østerud B, Kappelmayer J. Anti-β2-glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms. Thromb Res 2021; 197: 124-131
  • 81 Zuily S, Ait Aissa K, Membre A, Regnault V, Lecompte T, Wahl D. Thrombin generation in antiphospholipid syndrome. Lupus 2012; 21 (07) 758-760
  • 82 Kremers RMW, Zuily S, Kelchtermans H. et al. Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin. Blood Adv 2018; 2 (11) 1315-1324
  • 83 Billoir P, Miranda S, Damian L, Richard V, Benhamou Y, Le Cam Duchez V. Development of a thrombin generation test in cultured endothelial cells: evaluation of the prothrombotic effects of antiphospholipid antibodies. Thromb Res 2018; 169: 87-92
  • 84 Anderson L, Quasim I, Steven M. et al. Interoperator and intraoperator variability of whole blood coagulation assays: a comparison of thromboelastography and rotational thromboelastometry. J Cardiothorac Vasc Anesth 2014; 28 (06) 1550-1557
  • 85 Schöchl H, Forster L, Woidke R, Solomon C, Voelckel W. Use of rotation thromboelastometry (ROTEM) to achieve successful treatment of polytrauma with fibrinogen concentrate and prothrombin complex concentrate. Anaesthesia 2010; 65 (02) 199-203
  • 86 Dimitrova-Karamfilova A, Patokova Y, Solarova T, Petrova I, Natchev G. Rotation thromboelastography for assessment of hypercoagulation and thrombosis in patients with cardiovascular diseases. J Life Sci 2012; 6: 28-35
  • 87 Hincker A, Feit J, Sladen RN, Wagener G. Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery. Crit Care 2014; 18 (05) 549
  • 88 Kamel Y, Hassanin A, Ahmed AR. et al. Perioperative thromboelastometry for adult living donor liver transplant recipients with a tendency to hypercoagulability: a prospective observational cohort study. Transfus Med Hemother 2018; 45 (06) 404-412
  • 89 Hensch L, Kostousov V, Bruzdoski K. et al. Does rotational thromboelastometry accurately predict coagulation status in patients with lupus anticoagulant?. Int J Lab Hematol 2018; 40 (05) 521-526
  • 90 Fiol AG, Fardelmann KL, McGuire PJ, Merriam AA, Miller A, Alian A. The application of ROTEM in a parturient with antiphospholipid syndrome in the setting of anticoagulation for cesarean delivery: a case report. A Pract 2020; 14 (06) e01182
  • 91 Cucnik S, Kveder T, Krizaj I, Rozman B, Bozic B. High avidity anti-beta 2-glycoprotein I antibodies in patients with antiphospholipid syndrome. Ann Rheum Dis 2004; 63 (11) 1478-1482
  • 92 Thaler M, Buhl A, Welter H. et al. Biosensor analyses of serum autoantibodies: application to antiphospholipid syndrome and systemic lupus erythematosus. Anal Bioanal Chem 2009; 393 (05) 1417-1429
  • 93 Rawlings DJ, Metzler G, Wray-Dutra M, Jackson SW. Altered B cell signalling in autoimmunity. Nat Rev Immunol 2017; 17 (07) 421-436
  • 94 Žager U, Irman Š, Lunder M. et al. Immunochemical properties and pathological relevance of anti-β2-glycoprotein I antibodies of different avidity. Int Immunol 2011; 23 (08) 511-518
  • 95 Vlachoyiannopoulos PG, Petrovas C, Tektonidou M, Krilis S, Moutsopoulos HM. Antibodies to beta 2-glycoprotein-I: urea resistance, binding specificity, and association with thrombosis. J Clin Immunol 1998; 18 (06) 380-391
  • 96 Metzger J, von Landenberg P, Kehrel M, Buhl A, Lackner KJ, Luppa PB. Biosensor analysis of beta2-glycoprotein I-reactive autoantibodies: evidence for isotype-specific binding and differentiation of pathogenic from infection-induced antibodies. Clin Chem 2007; 53 (06) 1137-1143
  • 97 McDonnell T, Wincup C, Buchholz I. et al. The role of beta-2-glycoprotein I in health and disease associating structure with function: more than just APS. Blood Rev 2020; 39: 100610
  • 98 Szabó G, Pénzes K, Torner B. et al. Distinct and overlapping effects of β2-glycoprotein I conformational variants in ligand interactions and functional assays. J Immunol Methods 2020; 487: 112877