scholarly journals The Mosaic of “Seronegative” Antiphospholipid Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Fabrizio Conti ◽  
Antonella Capozzi ◽  
Simona Truglia ◽  
Emanuela Lococo ◽  
Agostina Longo ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
Annexin V ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dot Blot ◽  
Cardiolipin Antibodies ◽  
Lysobisphosphatidic Acid ◽  
Methodological Approaches ◽  
Antigenic Targets

In the clinical practice it is possible to find patients with clinical signs suggestive of antiphospholipid syndrome (APS), who are persistently negative for the laboratory criteria of APS, that is, anti-cardiolipin antibodies (aCL), anti-β2-GPI antibodies and lupus anticoagulant. Therefore, it was proposed for these cases the term of seronegative APS (SN-APS). In order to detect autoantibodies with different methodological approaches, sera from 24 patients with SN-APS were analysed for anti-phospholipid antibodies using TLC immunostaining, for anti-vimentin/cardiolipin antibodies by enzyme-linked immunosorbent assay (ELISA), and for anti-annexin V and anti-prothrombin antibodies by ELISA and dot blot. Control groups of our study were 25 patients with APS, 18 with systemic lupus erythematosus (SLE), and 32 healthy controls. Results revealed that 13/24 (54.2%) SN-APS sera were positive for aCL (9 of whom were also positive for lysobisphosphatidic acid) by TLC immunostaining, 11/24 (45.8%) for anti-vimentin/cardiolipin antibodies, 3/24 (12.5%) for anti-prothrombin antibodies, and 1/24 (4.2%) for anti-annexin V antibodies. These findings suggest that in sera from patients with SN-APS, antibodies may be detected using “new” antigenic targets (mainly vimentin/cardiolipin) or methodological approaches different from traditional techniques (mainly TLC immunostaining). Thus, SN-APS represents a mosaic, in which antibodies against different antigenic targets may be detected.

Vimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 2960-2967 ◽  
Author(s):  
Elena Ortona ◽  
Antonella Capozzi ◽  
Tania Colasanti ◽  
Fabrizio Conti ◽  
Cristiano Alessandri ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Surface Membrane ◽  
Clinical Signs ◽  
Nuclear Factor Κb ◽  
Endothelial Cell Surface ◽  
Proteomic Approach ◽  
Cardiolipin Antibodies ◽  
Almost All

AbstractAntiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial and venous thrombosis, recurrent abortions, and antiphospholipid antibodies (aPL). However, it is possible to find patients with clinical signs of APS who persistently test negative for aPL (seronegative APS, or SN-APS). The aim of this study was to identify new antigenic target(s) of autoantibodies in APS patients, which may also be recognized in SN-APS. We tested sera from patients with SN-APS with a proteomic approach by analyzing endothelial cell-surface membrane proteins. Sera from SN-APS patients revealed 2 reactive spots corresponding to vimentin, a protein that is shown to bind cardiolipin in vitro. Antivimentin/cardiolipin antibodies were tested in 29 SN-APS patients, 40 APS patients, 30 patients with systemic lupus erythematosus, 30 with rheumatoid arthritis, 30 with venous or arterial thrombosis, and 32 healthy control patients. We observed that not only a large proportion of SN-APS patients but also almost all the APS patients displayed the presence of antivimentin/cardiolipin antibodies. To verify the possible pathogenic role of these autoantibodies, we demonstrated that affinity-purified antivimentin/cardiolipin antibodies induced interleukin receptor-associated kinase phosphorylation and nuclear factor-κB activation in endothelial cells. Our results prompt to identify vimentin as a “new” cofactor for aPL, which may represent a useful tool mainly in SN-APS patients.

scholarly journals Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 107 (11) ◽  
pp. 4375-4382 ◽  
Author(s):  
Gabriela Cesarman-Maus ◽  
Nina P. Ríos-Luna ◽  
Arunkumar B. Deora ◽  
Bihui Huang ◽  
Rosario Villa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Healthy Individuals ◽  
Annexin 2

AbstractThe association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and β2-glycoprotein I (β2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti–A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold ± 0.13-fold SE), blocked A2-supported plasmin generation in a tPAdependent generation assay (19%-71%) independently of β2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.

Antiphospholipid syndrome – an update

VASA ◽  
2018 ◽  
Vol 47 (6) ◽  
pp. 451-464 ◽  
Author(s):  
Birgit Linnemann
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Heart Valve Disease ◽  
Small Vessels ◽  
Glycoprotein I ◽  
Neurologic Disorders ◽  
Cardiolipin Antibodies ◽  
Obstetric Aps ◽  
Beta 2

Abstract. Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired thrombophilia. It is characterized by the presence of antiphospholipid antibodies (APL) that are directed against phospholipid-binding plasma proteins, such as beta-2-glycoprotein I (b2GPI). Its main manifestations are recurrent vascular thromboses (so-called “thrombotic APS”) and pregnancy complications (“obstetric APS”). According to the current consensus criteria, a persistently positive functional lupus anticoagulant (LA) assay and/or the presence of anti-b2GPI and/or anti-cardiolipin antibodies, together with clinical symptoms, is mandatory for the diagnosis of APS. Other clinical features, such as thrombocytopenia, Coombs-positive haemolytic anaemia, heart valve disease, renal microangiopathy and neurologic disorders are also common in APL-positive patients. APS can be associated with other autoimmune disorders, such as systemic lupus erythematosus. In rare cases, catastrophic APS (CAPS) occurs, with the development of excessive thrombosis at multiple sites, usually affecting small vessels and leading to multi-organ dysfunction and organ failure. Treatment usually comprises antithrombotic therapy using antiplatelet and anticoagulant agents. However, there is no consensus concerning the intensity or duration of therapy. Despite apparently adequate anticoagulation, the risk of recurrent thrombosis remains high. For patients with CAPS, a combined therapeutic approach that includes anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulin seems to be the best treatment option. Keywords: Antiphospholipid syndrome, lupus anticoagulants, anti-cardiolipin, anti-beta-2-glycoprotein I, vascular thrombosis, pregnancy complication

Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3677-3683 ◽  
Author(s):  
Sanjay Rajagopalan ◽  
Emily C. Somers ◽  
Robert D. Brook ◽  
Christine Kehrer ◽  
Dana Pfenninger ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Endothelial Cell ◽  
Lupus Erythematosus ◽  
Vascular Function ◽  
Annexin V ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Framingham Risk ◽  
Healthy Control ◽  
Artery Disease

Abstract Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, and subjects with coronary artery disease (CAD) (n = 43/group). Quantification of circulating apoptotic ECs was performed by flow cytometry (CD146+ cells that stained for Annexin V [CD146AnnV+]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146AnnV+ cells (10 ± 3, 18 ± 5, and 89 ± 32 cells/mL, respectively, mean ± SEM; P &lt; .01). Increased CD146AnnV+ cells correlated strongly with abnormal vascular function (P = .037). After adjusting for known predictors of endothelial function, CD146AnnV+ was the only variable that predicted FMD (β = –4.5, P &lt; .001). Increased CD146AnnV+ was strongly associated with elevated levels of circulating TF (r = .46, P = .002). Circulating apoptotic ECs are elevated in young women with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of atherothrombosis in SLE.

Annexin V antibodies in multiple sclerosis and SLE/APS

Open Medicine ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. 225-228
Author(s):  
Marta Baleva ◽  
Detelina Stoilova ◽  
Petko Shotekov ◽  
Krasimir Nikolov
Keyword(s):  
Multiple Sclerosis ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Annexin V ◽  
Serum Levels ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Pathogenic Role ◽  
Glycoprotein I

AbstractMultiple sclerosis (MS) is an autoimmune disease with unclear etiopathogenesis. Some MS patients have anticardiolipin (ACL), anti-beta-2-glycoprotein-I (B2GPI) and anti-annexin V (AnV) antibodies. These antibodies can also be found in systemic lupus erythematosus with antiphospholipid syndrome (SLE/APS). The aim of our study was to compare the levels of ACL, B2GPI and AnV antibodies in MS and SLE/APS. Materials and methods: We investigated serum levels of IgG and IgM ACL, B2GPI and AnV in 21 MS patients, 30 SLE/APS patients and 30 controls using ELISA. Results: Mean levels of IgM and IgG ACL and B2GPI in MS were comparable with controls and lower than SLE/APS (p<0.05). Mean levels of IgM AnV in MS were higher compared to SLE/APS and controls (p<0.05); mean levels of IgG AnV in MS were higher than normal but similar to SLE/APS (p>0.05). Discussion: The results show that MS with negative “classic” autoantibodies (ACL and B2GPI) and without clinical data for antiphospholipid syndrome may have other positive antiphospholipid antibodies, such as AnV. Larger studies are needed to clarify whether AnV are epiphenomenon of the vascular and organ damage or they play a pathogenic role in the development of MS.

TECHNIQUES OF MODIFYING LIPID ANTIGENS FOR SYNTHESIS OF DIAGNOSTIC AND THERPAEUTIC PREPARATIONS IN RHEUMATOLOGY

2019 ◽  
Vol 64 (10) ◽  
pp. 603-606
Author(s):  
I. P. Gontar ◽  
Oiga Ivanovna Emelyanova ◽  
O. A. Rusanova ◽  
I. A. Zborovskay ◽  
N. I. Emelyanov
Keyword(s):  
Emulsion Polymerization ◽  
Sorption Capacity ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Solid Phase ◽  
Particle Diameter ◽  
Healthy Individuals ◽  
Sorptive Capacity ◽  
Clinical Presentations ◽  
Cardiolipin Antibodies

The objective of the study is to enhance sorption capacity of diagnostic agents by using cardiolipin antigens for antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE). A technique of emulsion polimerization was used. Having integrated antigen nanoobjects we developed immobilized magnetocontrollable antigen nanosystems and put them to an evaluation test. The nanosystems are polyacrylamide granules with a built in antigen. To obtain stable immobilized multi-use biopharmaceuticals with targeted properties (shape, particle diameter, pore size, density) we used a modified version of emulsion polymerization method using polyacrylamide carrier gel. This method permitted a greater sorptive capacity, preserving the antigen in maximum native state, and opened up the possibility of controllable modification of nanoobjects. Cardiolipin was used as the antigen in question. Following the method described above we performed sorption of anticardiolipin antibodies from blood plasma of SLE patients who showed clinical presentations of antiphospholipid syndrome. All SLE patoents with signs of antiphospholipid syndrome showed reliably higher levels of cardiolipin antibodies compared with SLE patients without antiphospholipid syndrome signs; the antibody level was 0.365 ± 0.026 and 0.075 ± 0.003 on average, correspondingly (p < 0.001). Blood serum from 10 apparently healthy individuals served as control. The level of cardiolipin antibodies was determined before and after sorption by indirect solid phase immunoenzyme method. In the eluate we estimated total protein by Lowry method. In vitro testing showed that the obtained antigen nanosystems based on immobilized cardiolipin could effectively remove cardiolipin antibodies from whole blood of SLE patients with clinical presentations of APS to achieve the values of healthy individuals (before sorption cardiolipin antibodies 0.328 ± 0.0289; after sorption 0.059 ± 0.0170; p<0,001; sorption capacity 8.00 ± 0.390 mg/ml). The method of emulsion polymerization with consideration to hydrophobic and hydrophilic properties of lipid molecules permits obtaining and modifying biomolecules with certain properties, in a controlled fashion.

scholarly journals “New” Antigenic Targets and Methodological Approaches for Refining Laboratory Diagnosis of Antiphospholipid Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Roberta Misasi ◽  
Antonella Capozzi ◽  
Agostina Longo ◽  
Serena Recalchi ◽  
Emanuela Lococo ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
New Technologies ◽  
Solid Phase ◽  
Protein S ◽  
Laboratory Diagnosis ◽  
Diagnostic Value ◽  
Anticardiolipin Antibodies ◽  
Special Focus ◽  
Methodological Approaches ◽  
Antigenic Targets

Antiphospholipid antibodies (aPLs) are a heterogeneous group of antibodies directed against phospholipids or protein/phospholipid complexes. Currently, aPLs are assessed using either “solid-phase” assays that identify anticardiolipin antibodies and anti-β2-glycoprotein I antibodies or “liquid-phase” assay that identifies lupus anticoagulant. However, in the last few years, “new” antigenic targets and methodological approaches have been employed for refining laboratory diagnosis of antiphospholipid syndrome (APS). In this review the potential diagnostic value of antibodies to domains ofβ2-GPI, prothrombin/phosphatidylserine, vimentin/cardiolipin, protein S, protein C, annexin A2, annexin A5, and phospholipid antigens is discussed. Moreover, new technical approaches, including chemiluminescence, multiline dot assay, and thin layer chromatography (TLC) immunostaining, which utilize different supports for detection of aPL, have been developed. A special focus has been dedicated on “seronegative” APS, that is, those patients with a clinical profile suggestive of APS (thromboses, recurrent miscarriages, or foetal loss), who are persistently negative for the routinely used aPL. Recent findings suggest that, in sera from patients with SN-APS, antibodies may be detected using “new” antigenic targets (mainly vimentin/cardiolipin) or methodological approaches different from traditional techniques (TLC immunostaining). Thus, APS represents a mosaic, in which antibodies against different antigenic targets may be detected thanks to the continuously evolving new technologies.

Antibody-Mediated Disruption of the Annexin-V Antithrombotic Shield: A New Mechanism for Thrombosis in the Antiphospholipid Syndrome

1999 ◽  
Vol 82 (08) ◽  
pp. 649-655 ◽  
Author(s):  
Xiao-Xuan Wu ◽  
Jacob Rand
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Protein Complexes ◽  
Annexin V ◽  
Autoimmune Disorder ◽  
Antigenic Determinants ◽  
Anionic Phospholipid

IntroductionThe antiphospholipid (aPL) syndrome is a condition that manifests in patients as vascular thromboembolism or recurrent pregnancy loss together with laboratory evidence for the presence of antibodies against anionic phospholipid-protein complexes. For a recent comprehensive review, the reader is referred to Hughes et al.1 The syndrome was first proposed to be a distinct entity, called anticardiolipin syndrome, in 1985,2 and was later renamed antiphospholipid syndrome.3 The disorder was classified as “primary” in the absence of a concurrent autoimmune condition, such as systemic lupus erythematosus, or “secondary” in the presence of another such autoimmune disorder. Antiphospholipid antibodies are detected by their reactivity to anionic phospholipids (or protein-phospholipid complexes) in solid phase immunoassays, or by their inhibition of phospholipid-dependent coagulation reactions, known as the “lupus anticoagulant” effect. The ever-expanding, yet still insufficiently integrated, knowledge of this enigmatic disorder makes this area an intriguing subject for investigation.The pathophysiologic mechanism of this syndrome has remained obscure, resulting from the apparent multiplicity of antigenic determinants recognized by the antibodies. In addition, a large number of effects1 have been described for the antibodies in vitro and in cell culture systems. These effects, which include the paradoxical lupus anticoagulant (LAC) phenomenon, are a consequence of the numerous roles played by phospholipids in the hemostasis system and in a multitude of biologic processes. The purpose of this review is to introduce the reader to the current state of knowledge of the role of annexin-V in this disorder.

scholarly journals AB0078 LIPID IMMOBILIZATION AS A METHOD TO OBTAIN ANTIGENIC NANO-OBJECTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1069.1-1069
Author(s):  
O. Rusanova ◽  
O. Emelyanova ◽  
N. Emelyanov
Keyword(s):  
Emulsion Polymerization ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Active Sites ◽  
Solid Phase ◽  
Particle Diameter ◽  
Healthy Individuals ◽  
Sorptive Capacity ◽  
Clinical Presentations ◽  
Cardiolipin Antibodies

Objectives:Objective of the study is to research the effect of emulsion polymerization on active sites of cardiolipin antigen determinant in antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE).Methods:Having integrated antigen nanoobjects we developed immobilized magnetocontrollable antigen nanosystems and put them to an evaluation test. The nanosystems are polyacrylamide granules with a built in antigen. To obtain stable immobilized multi–use biopharmaceuticals with targeted properties (shape, particle diameter, pore size, density) we used a modified version of emulsion polymerization method using polyacrylamide carrier gel. This method permitted a greater sorptive capacity, preserving the antigen in maximum native state, and opened up the possibility of controllable modification of nanoobjects. Cardiolipin was used as the antigen in question.Results:Following the method described above we performed sorption of anticardiolipin antibodies from blood plasma of SLE patients who showed clinical presentations of antiphospholipid syndrome. Blood serum from 10 apparently healthy individuals served as control. The level of cardiolipin antibodies was determined before and after sorption by indirect solid phase immunoenzyme method. In the eluate we estimated total protein by Lowry method. In vitro testing showed that the obtained antigen nanosystems based on immobilized cardiolipin could effectively remove cardiolipin antibodies from whole blood of SLE patients with clinical presentations of APS to achieve the values of healthy individuals (before sorption cardiolipin antibodies 0.328 ± 0.028; after sorption 0.059 ± 0.017; p<0.001; sorption capacity 8.00 ± 0.390 mg/ml).Conclusion:The method of emulsion polymerization with consideration to hydrophobic and hydrophilic properties of lipid molecules permits obtaining and modifying biomolecules with certain properties, in a controlled fashion.Disclosure of Interests:None declared

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