Clinical significance of β2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: Correlation with conventional antiphospholipid antibody detection systems

1995 ◽  
Vol 172 (3) ◽  
pp. 926-931 ◽  
Author(s):  
Koji Aoki ◽  
Alan B. Dudkiewicz ◽  
Eiji Matsuura ◽  
Marilyn Novotny ◽  
George Kaherlein ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Anticardiolipin Antibodies ◽  
Antibody Detection ◽  
Antiphospholipid Antibody ◽  
Detection Systems ◽  
Glycoprotein I

Standardization of Antiphospholipid Antibody Testing—Historical Perspectives and Ongoing Initiatives

2014 ◽  
Vol 40 (02) ◽  
pp. 172-177 ◽  
Author(s):  
Rohan Willis ◽  
Gabriella Lakos ◽  
E. Harris
Keyword(s):  
Clinical Significance ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Task Force ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antibody Testing ◽  
Historical Perspectives ◽  
The Past ◽  
Glycoprotein I

The measurement of antiphospholipid antibodies (aPL) has been an important aspect of antiphospholipid syndrome (APS) characterization since the disease was first described in the 1980s. Despite significant efforts geared toward the standardization of immunoassays that measure anticardiolipin antibodies and anti-β2-glycoprotein I spanning three decades, there are still reports of significant interassay and interlaboratory variation in the results of these assays. At the recent 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX), a task force composed of internationally recognized experts in the field of APS was formed to address these issues. In this review, we discuss approaches that have been used in the past to achieve harmonization among aPL immunoassays as well as the ongoing efforts of the APLA task force. Our review also highlights the importance of cutoff determination in aPL assays and the clinical significance of positive aPL results of varying magnitudes.

Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1178-1183 ◽  
Author(s):  
Monica Galli ◽  
Giovanna Borrelli ◽  
Eva Marie Jacobsen ◽  
Rosa Maria Marfisi ◽  
Guido Finazzi ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Significance ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igm Antibodies ◽  
Glycoprotein I

Abstract To assess the clinical significance of lupus anticoagulants (LAs) and antiphospholipid antibodies (aPLs) toward thrombosis and abortions, we measured them in 112 patients whose samples were available at enrollment in the warfarin in the antiphospholipid syndrome (WAPS) study. Enzyme-linked immunosorbent assay (ELISA) and coagulation test values in the highest and lowest tertiles were compared. When considered separately, IgG antibodies to β2-glycoprotein I (aβ2GPI) and prothrombin (aPT) were associated with anamnestic arterial and venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions. IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time were associated with prospective thrombosis. No other association for IgM antibodies was seen. LA-positive patients who carried aβ2GPI antibodies were at risk of anamnestic arterial and total thrombosis and aPT antibodies to that of anamnestic venous and total thrombosis. LA-positive patients who carried IgG aβ2GPI and aAnAV antibodies were at risk for both anamnestic abortion and prospective thrombosis. Overall, these data support the inclusion of aβ2GPI antibodies in and suggest the removal of anticardiolipin antibodies from the laboratory criteria of the antiphospholipid syndrome. They also suggest that the measurement of aPT and aAnAV antibodies is useful in some selected situations and that there is little role for IgM antibody detection.

Anti-β2-glycoprotein I antibodies

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 98-102 ◽  
Author(s):  
A Tsutsumi ◽  
K Ichikawa ◽  
E Matsuura ◽  
T Koike
Keyword(s):  
Enzyme Immunoassay ◽  
Clinical Significance ◽  
Great Care ◽  
Detection Systems ◽  
Glycoprotein I ◽  
History Of ◽  
Reproducible Method ◽  
Set Up ◽  
The Relationship

The relationship between presence of anti-β2-glycoprotein I autoantibodies (aβ2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of aβ2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of aβ2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of aβ2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.

Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus

Blood ◽  
2005 ◽  
Vol 106 (13) ◽  
pp. 4152-4158 ◽  
Author(s):  
Christoph Male ◽  
Denise Foulon ◽  
Hugh Hoogendoorn ◽  
Patricia Vegh ◽  
Earl Silverman ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Diagnostic Value ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Systemic Lupus ◽  
Glycoprotein I ◽  
Strength Of Association

Study objectives were to determine, in children with systemic lupus erythematosus (SLE), (1) the association of antiphosholipid antibody (APLA) subtypes with thrombotic events (TEs) and (2) the predictive value of persistent versus transient antibodies for TEs. This is a cohort study of 58 SLE children in whom lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), anti–β2-glycoprotein-I (anti–β2-GPI), and antiprothrombin (anti-PT) were assessed on at least 2 occasions (more than 3 months apart). Antibodies were classified as persistent (positive on at least 2 occasions) or transient (positive once). Outcomes were symptomatic TEs confirmed by objective radiographic tests identified retrospectively and prospectively. Seven of the 58 patients (12%) had 10 TEs; 5 patients had TEs during prospective follow-up. Persistent LAs showed the strongest association with TEs (P < .001). Persistent ACLAs (P = .003) and anti–β2-GPI (P = .002) were significantly associated with TEs; anti-PT (P = .063) showed a trend. Persistent or transient LAs and anti–β2-GPI showed similar strength of association, while ACLAs and anti-PT were no longer associated with TEs. Positivity for multiple APLA subtypes showed stronger associations with TEs than for individual APLA subtypes because of improved specificity. Lupus anticoagulant is the strongest predictor of the risk of TEs; other APLA subtypes provide no additional diagnostic value. Anticardiolipin antibodies and anti-PT require serial testing because only persistent antibodies are associated with TEs.

Antiphospholipid Antibody Syndrome

2011 ◽  
Vol 135 (9) ◽  
pp. 1092-1096 ◽  
Author(s):  
Nikhil A Sangle ◽  
Kristi J Smock
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Protein Complexes ◽  
Anticardiolipin Antibodies ◽  
Clinical Aspects ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Laboratory Results

Antiphospholipid antibodies are directed against phospholipid-protein complexes and include lupus anticoagulant, anticardiolipin antibodies, and anti–beta-2 glycoprotein I antibodies. Antiphospholipid antibody syndrome is a common cause of acquired thrombophilia and is characterized by venous or arterial thromboembolism or pregnancy morbidity and the presence of antiphospholipid antibodies. Antibodies should be demonstrable on at least 2 occasions separated by 12 weeks. Heterogeneity of the autoantibodies and absence of gold standard assays makes interpretation of laboratory results a challenge for both laboratorians and clinicians. This review discusses the key laboratory and clinical aspects of antiphospholipid antibody syndrome. Particular focus is given to lupus anticoagulant detection, in view of recently updated laboratory guidelines.

scholarly journals CLINICAL AND IMMUNOLOGICAL CORRELATIONS IN PATIENTS WITH SYSTEMICLUPUS ERYTHEMATOSUS WITH ANTIPHOSPHOLIPID ANTIBODY SYNDROME

2017 ◽  
Vol 9 (3) ◽  
pp. 7-11 ◽  
Author(s):  
E A Belolipetskaia ◽  
I B Beliaeva ◽  
V I Mazurov ◽  
E A Trofimov ◽  
S V Lapin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Annexin V ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Systemic Lupus ◽  
Glycoprotein I ◽  
Threefold Increase

Antiphospholipid antibodies (aPL): lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (anti-β2GPI) are found in 12 to 44% of systemic lupus erythematosus (SLE) patients. On average, antiphospholipid antibody syndrome (APS) develops in50% of aPL-positive patients with SLE. The seronegative APS is characterized by the absence of the diagnostic levels of "classical" aPL and by the presence of non-criteria aPL: antibodies against pro- thrombin (aPT), antibodies against annexin V, antibodies against phosphatidylethanoamine (aPE), antibodies to phosphatidylserine/prothrombin complex (aPS-PT) and antibodies against negatively charged phospholipids. The presence of four antibodies (LA + aCT + anti-β2GPI + aPT) is associated with a threefold increase in the risk of thrombosis. The presence of aCL and anti-β2GPI in SLE patients with APS and recurrent thromboses is associated with the HLA dRB1 * 0402.

scholarly journals COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?

2021 ◽  
Author(s):  
Emmanuel J. Favaloro ◽  
Brandon Michael Henry ◽  
Giuseppe Lippi
Keyword(s):  
Antiphospholipid Antibodies ◽  
Solid Phase ◽  
High Titer ◽  
Severe Form ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Glycoprotein I ◽  
Autoimmune Conditions ◽  
Antiprothrombin Antibodies

AbstractAntiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as “noncriteria antibodies.” The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified “solid-phase” aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients.

Heterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies

1998 ◽  
Vol 80 (09) ◽  
pp. 393-398 ◽  
Author(s):  
V. Regnault ◽  
E. Hachulla ◽  
L. Darnige ◽  
B. Roussel ◽  
J. C. Bensa ◽  
...  
Keyword(s):  
Fluid Phase ◽  
Anticardiolipin Antibodies ◽  
Dual Reactivity ◽  
Group Iii ◽  
Important Group ◽  
Epitope Specificity ◽  
Glycoprotein I ◽  
Group I ◽  
Group Ii ◽  
Sufficient Concentration

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.

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