Serum Anti-β2-glycoprotein I Antibodies from Patients with Antiphospholipid Antibody Syndrome Bind Central Nervous System Cells

1998 ◽  
Vol 11 (5) ◽  
pp. 425-429 ◽  
Author(s):  
Brunella Caronti ◽  
Caterina Calderaro ◽  
Cristiano Alessandri ◽  
Fabrizio Conti ◽  
Raffaella Tinghino ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Glycoprotein I

International Normalized Ratio (INR) Determined by Plasma-Based Methods Versus Point-of-Care Instruments in Patients with Antiphospholipid Antibody Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1067-1067 ◽  
Author(s):  
Stephan Moll ◽  
Lauren McKnight ◽  
Allison Deal
Keyword(s):  
Point Of Care ◽  
Clinical Decision ◽  
Analysis Data ◽  
International Normalized Ratio ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Factor X ◽  
Research Support ◽  
Glycoprotein I ◽  
Factor Ii

Abstract Abstract 1067 Poster Board I-89 Background: In some patients with antiphospholipid antibody (APLA) syndrome treated with warfarin, the International Normalized Ratios (INRs) obtained from plasma, as well as from full blood via fingerstick by older point-of-care (POC) devices, are unreliable. Reliability of newer POC devices in APLA syndrome patients is unknown and was investigated in the present study. Methods: 60 patients on stable warfarin were enrolled: 30 with APLA syndrome, 30 without. INRs were determined using 4 POCs: CoaguChekXS®, ProTime®, the investigational ProTime®, and INRatio2®. Plasma from phlebotomy was tested for: PT, factor II activity, chromogenic factor X, anticardiolipin and anti-beta-2-glycoprotein I antibodies, lupus anticoagulant. Analysis: Data from the venipuncture INRs from the patients without APLA are used to estimate the relationship between INR and Factor II level and determine the therapeutic range of Factor II. Using the same therapeutic INR range, for each individual POC test the proportion of patients whose clinical decision based on the POC instrument is correct is estimated, along with 95% confidence intervals. This is done for patients with and without APLA. These two proportions are compared between the two groups using Fisher's Exact Tests; nominal p-values are reported. A similar analysis is done using the Factor X test as the gold standard. Results: Data collection has been completed; analysis of results is pending and will be available before December 2009. Conclusions: Data analysis will show whether the presently available POC devices give reliable INR results in patients with APLA syndrome on warfarin and can be reliably used to monitor warfarin therapy. Disclosures: Moll: Hemosense: research support; Roche: reserarch support; ITC: Consultancy, research support. McKnight:ITC: Honoraria. Deal:ITC: Consultancy.

scholarly journals Pathophysiology of the Antiphospholipid Antibody Syndrome

2021 ◽  
Author(s):  
David Green
Keyword(s):  
Antiphospholipid Syndrome ◽  
Binding Proteins ◽  
Membrane Receptors ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Clotting Factors ◽  
Anionic Phospholipid ◽  
Autoantibody Production ◽  
Phospholipid Binding ◽  
Glycoprotein I

The antiphospholipid syndrome is characterized by antibodies directed against phospholipid-binding proteins and phospholipids attached to cell membrane receptors, mitochondria, oxidized lipoproteins, and activated complement components. When antibodies bind to these complex antigens, cells are activated and the coagulation and complement cascades are triggered, culminating in thrombotic events and pregnancy morbidity that further define the syndrome. The phospholipid-binding proteins most often involved are annexins II and V, β2-glycoprotein I, prothrombin, and cardiolipin. A distinguishing feature of the antiphospholipid syndrome is the “lupus anticoagulant”. This is not a single entity but rather a family of antibodies directed against complex antigens consisting of β2-glycoprotein I and/or prothrombin bound to an anionic phospholipid. Although these antibodies prolong in vitro clotting times by competing with clotting factors for phospholipid binding sites, they are not associated with clinical bleeding. Rather, they are thrombogenic because they augment thrombin production in vivo by concentrating prothrombin on phospholipid surfaces. Other antiphospholipid antibodies decrease the clot-inhibitory properties of the endothelium and enhance platelet adherence and aggregation. Some are atherogenic because they increase lipid peroxidation by reducing paraoxonase activity, and others impair fetal nutrition by diminishing placental antithrombotic and fibrinolytic activity. This plethora of destructive autoantibodies is currently managed with immunomodulatory agents, but new approaches to treatment might include vaccines against specific autoantigens, blocking the antibodies generated by exposure to cytoplasmic DNA, and selective targeting of aberrant B-cells to reduce or eliminate autoantibody production.

Utilization of Dilute Russell’s Viper Venom Time to Detect Autoantibodies against β2-Glycoprotein I which Express Anticoagulant Activity in the Presence but not in the Absence of Exogenous Phospholipids

1997 ◽  
Vol 77 (01) ◽  
pp. 123-126 ◽  
Author(s):  
V Pengo ◽  
G Balestrieri ◽  
A Tincani ◽  
L Spatola ◽  
A Biasiolo ◽  
...  
Keyword(s):  
Anticoagulant Activity ◽  
General Term ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Igg Antibody ◽  
Glycoprotein I ◽  
Specific Category ◽  
Coagulation Tests ◽  
Antibody Elisa ◽  
Presence And Absence

SummaryLupus anticoagulant (LA) is a general term to define immunoglobulins interfering with phospholipid-dependent coagulation tests. It is now clear that the phospholipid-dependence of some LA is related to the presence of the phospholipid-binding plasma protein β2-glycoprotein I β2-GPI) and that autoantibodies to β2-GPI might represent a specific category of LA. To verify this hypothesis we have purified IgG autoantibodies to β2-GPI from plasma of 6 patients with antiphospholipid antibody syndrome, by means of agarose-immobilized human β2-GPI. All 6 preparations tested positive in anti-β2-GPI IgG antibody ELISA and showed a marked LA activity by prolonging dilute Russell Viper Venom Time (dRVVT) from a minimum of 5.3 s in patient # 1 to a maximum of 41.1 s in patient # 3. These IgG preparations behaved as typical LA, with this activity tending to disappear in the presence of increasing phospholipid (PL) concentrations. Moreover, the LA activity of the IgG preparations was not detectable in the absence of PL, in which case the ratio between dRVVT obtained in the presence and absence of IgG autoantibodies to β2-GPI was close to 1. This pattern was confirmed by using plasma from patients with antiphospholipid antibody syndrome testing positive for anti-β2-GPI IgG antibodies. These findings suggest that dRVVT performed both in the presence and absence of PL might constitute a sensitive screening test to detect specific antibodies with LA activity.

scholarly journals Phospholipid Autoantibodies and the Antiphospholipid Antibody Syndrome: Diagnostic Accuracy of 23 Methods Studied by Variation in ROC Curves with Number of Clinical Manifestations

2002 ◽  
Vol 48 (7) ◽  
pp. 1004-1010 ◽  
Author(s):  
Jan-Christian Wasmuth ◽  
Desamparados Oliver y Miñarro ◽  
Angela Homrighausen ◽  
Ludger Leifeld ◽  
Jürgen K Rockstroh ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Roc Curves ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Test Results ◽  
Glycoprotein I ◽  
Immunoglobulin Isotypes ◽  
The Individual

Abstract Background: We analyzed the diagnostic accuracies for the diagnosis of antiphospholipid syndrome (APS) of 23 antiphospholipid antibody (APL-Ab) assays targeted at different antigen preparations and immunoglobulin isotypes. Methods: In 144 patients with suspected APS, anti-cardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies were measured with 23 different ELISAs from three manufacturers. Data were analyzed by ROC curves. In the absence of an accepted criterion standard, the endpoint “diagnosis of APS” was varied according to the number (two through five) of signs and symptoms of APS. Results: Although the presence of lupus anticoagulant was associated significantly with APL-Ab in 10 of 23 assays (P = 0.01–10−4) and recurrent arterial or venous occlusions were significantly associated with APL-Ab of IgM isotype in 5 of 6 assays (P = 0.02–10−4), sensitivity for detection of APS did not exceed 67%. With the exception of IgA APL-Ab, the diagnostic accuracy of the assays improved when the diagnosis of APS was based on an increasing number of simultaneous features of APS. For most methods, areas under the ROC curves were >0.8 irrespective of the method’s subclass specificity and antigen preparation (aCL or aβ2GPI), if the clinical diagnosis of APS was based on four or more signs and symptoms of APS. Conclusion: Despite considerable heterogeneity in the individual test results, a single test of IgG or IgM isotype targeted at either aCL or aβ2GPI antibodies has excellent diagnostic accuracy when the criterion for diagnosis requires four or more typical manifestations of APS.

scholarly journals Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

2019 ◽  
Vol 59 (1) ◽  
Author(s):  
Sandra Lúcia Euzébio Ribeiro ◽  
Helena Lúcia Alves Pereira ◽  
Antonio Luiz Boechat ◽  
Neusa Pereira Silva ◽  
Emilia Ionue Sato ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Specific Treatment ◽  
Binary Logistic Regression ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Leprosy Patients ◽  
Immunological Factors ◽  
Bacterial Index

Abstract Introduction Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives To determine whether epidemiological, clinical and immunological factors played a role in the long-term persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82–0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0–0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03–7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

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