Antibodies to Domain I of β2Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS)

Banzato, Alessandra; Pozzi, Nicola; Frasson, Roberta; Filippis, Vincenzo De; Ruffatti, Amelia; Bison, Elisa; Padayattil, Seena Jose; Denas, Gentian; Pengo, Vittorio

doi:10.1016/j.thromres.2011.04.021

Cited by 73 publications

(65 citation statements)

References 24 publications

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“…8 The presence of antibodies to DmI in triple positive APS patients has recently been shown by our group by means of a competitive ELISA using synthetic DmI. 9 In conclusion, triple positivity resemble patients with a true autoimmune disease as the main autoantibody (ab2GPI) is identified, the corresponding target antigen is known and an analogous response (antibodies against injected b2GPI) causes a similar disease in experimental animals. (Table 1 3,6,11,12 ).…”

mentioning

confidence: 79%

Interpretation of laboratory data and need for reference laboratories

Pengo

Denas

Banzato

et al. 2012

Lupus

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A single positive laboratory test among those exploring the presence of antiphospholipid antibodies is not associated with thromboembolic events and does not identify patients with antiphospholipid syndrome. On the other hand, more than one laboratory test positive, and in particular all three tests positive, is strongly associated to thromboembolic events and identifies high risk patients. Triple positivity is in fact related to the presence of a specific anti-b2-glycoprotein I (anti-Domain I) antibody, also able to prolong coagulation tests. Monoclonal antibodies against Domain I with Lupus Anticoagulant activity might be candidate material for standardization of antiphospholipid assays. Much work remains to be done in this field. Lupus (2012) 21, 732-733.

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mentioning

confidence: 79%

Interpretation of laboratory data and need for reference laboratories

Pengo

Denas

Banzato

et al. 2012

Lupus

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“…The significance of b 2 GPI independent LAC activity or aCL antibodies is under scrutiny. It is suggested that a specific subtype of antibodies (anti domain I type) responsible for thrombosis are detected when all the three tests are positive and it has been shown that triple positive patients have higher titer of anti domain I antibodies compared to double or single positive patients [19,20]. Based on these studies, it has been proposed to differentiate high risk triple positive APS patients from others [20] or to categorize APS into definite (triple positive), probable (dual positive) and possible or non-APS (single positive) [21].…”

Section: Issues With the Current Diagnostic Criteria Of Aps And Propomentioning

confidence: 99%

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Ahluwalia

Sreedharanunni

2016

Indian J Hematol Blood Transfus

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The Antiphospholipid Syndrome (APS) is classified based on the presence of both clinical and laboratory criteria. Both sets of criteria are subject to much review and intense research as it is becoming increasingly clear that no single test is specific for defining this autoimmune disorder. A number of leading international bodies have released guidelines in an attempt to improve the laboratory testing and reporting. The current review is an appraisal of some of the literature pertaining to the laboratory testing.

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“…In the UK, Escherichia coli was used as the expressing host to synthetize DI, and a direct ELISA test was then developed [39]. An italian group synthesized DI chemically, exploting it to set up a capture ELISA method using N-terminally biotinylated DI on streptavidin plates, and a liquid phase inhibition assay using whole β 2 GPI immobilized on the solid phase and synthetic β 2 GPI-DI as inhibitor [40,41]. INOVA Diagnostics (San Diego, USA) has developed two tests to detect anti-DI antibodies: a commercial anti-DI assay and a β 2 GPI-DI chemiluminescence immunoassay (CIA).…”

Section: Tests Detecting Anti-domain I Antibodiesmentioning

confidence: 99%

“…It is well established that patients with positivity in all the three criteria tests are at the highest risk of developing clinical events [49]. Banzato et al observed, using an inhibition ELISA test with a synthetic DI, that triple-positive patients carry significantly higher anti-DI antibody titres compared to doubleor single-positive subjects or healthy controls [41]. This finding might imply that anti-DI IgG may represent a more predictive aPL profile, and that anti-DI antibodies might be helpful in the risk-stratification of APS subjects.…”

Section: Anti-domain I β 2 Glycoprotein I Antibodies In Apsmentioning

confidence: 99%

Reactivity against the Five Domains of β2 Glycoprotein I: A Focus on Systemic Lupus Erythematosus

Chighizola¹,

Borghi²,

Grossi³

et al. 2014

J Clin Cell Immunol

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Beta-2 glycoprotein I (β 2 GPI) is the main antigenic target for antiphospholipid antibodies (aPL), the serological markers of antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy morbidity. aPL are detected in 20 to 50% of patients with systemic lupus erythematosus (SLE), representing a poor prognostic factor. Indeed, thrombotic events heralds high morbidity and mortality, being regarded as the strongest predictors of death in the first five years after SLE onset. It would be thus very important to identify a reliable laboratory tool such as anti-domain antibodies to better risk-stratify lupus patients according to the aPL profile, in order to tailor treatment strategies. Domain I (DI) of β 2 GPI has lately been identified as the main epitope targeted by antibodies reacting against β 2 GPI isolated from APS patients, well correlating with thrombotic as well as obstetric manifestations. Interestingly, anti-DI antibodies have been shown to well correlate with lupus anticoagulant and to predict the clinical manifestations of the syndrome, thrombotic events as well as pregnancy complications. Further, anti-DI antibodies allow to identify patients at highest clinical risk, presenting a good specificity for APS. On the other hand, anti-β 2 GPI antibodies from aPL asymptomatic carriers or subjects with infectious diseases preferentially display reactivity towards DIV or DV of the molecule.Few studies have to date evaluated the domain profile of anti-β 2 GPI antibodies in subjects with SLE, even though it would be very relevant from a clinical point of view to understand whether among patients with SLE the domain specificities of anti-β 2 GPI antibodies display a clinical meaning comparable to the one they exert in APS. It is therefore rather appropriate to review the available evidence about anti-domain specificities with a particular focus on SLE.

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Antibodies to Domain I of β2Glycoprotein I are in close relation to patients risk categories in Antiphospholipid Syndrome (APS)

Cited by 73 publications

References 24 publications

Interpretation of laboratory data and need for reference laboratories

Interpretation of laboratory data and need for reference laboratories

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Reactivity against the Five Domains of β2 Glycoprotein I: A Focus on Systemic Lupus Erythematosus

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