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 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

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

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.

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 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.

Sudden Sensorineural Hearing Loss in Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Clinical Review

2020 ◽  
Vol 16 (2) ◽  
pp. 84-91
Author(s):  
Julia L. Riera ◽  
María del R. Maliandi ◽  
Jorge L. Musuruana ◽  
Javier A. Cavallasca
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Clinical Feature ◽  
Systemic Lupus ◽  
Bilateral Involvement

Background: Sudden sensorineural hearing loss (SSNHL) is defined as a sudden loss of hearing, usually unilateral, of more than 30 dB in 3 contiguous frequencies of the tonal audiometry. SSNHL estimates an incidence ranging from 5 to 20 per 100.000 people per year. In approximately 75% of cases, a cause cannot be identified. However, it could be a clinical manifestation of Systemic lupus erythematosus (SLE) and Antiphospholipid Syndrome (APS). Objective: This review will focus on the clinical presentation, diagnosis, and management of the SLE and APS associated SSNHL. Methods: We searched in PubMed, Scopus, Lilacs, and Cochrane reviewing reports of Sudden sensorineural hearing loss in SLE and/or APS. Articles written in English and Spanish, and were available in full text, were included. Results: In patients with SLE, bilateral involvement was frequent. Antiphospholipid antibodies were positive in the majority of the patients. Corticosteroids were the mainstay of the treatment. The auditory prognosis was poor with total hearing loss recovery reached in only 22% of patients. : On the other hand, most of the patients with SSNHL and APS were males and presented associated symptoms such as vertigo, tinnitus and/or headache, 75% had bilateral disease. Lupus anticoagulant and aCL were found in equal proportions, all patients were anticoagulated, and aspirin was associated in 25% of the cases. Complete resolution or improvement of symptoms was observed in 25% of the patients. Conclusion: Sudden sensorineural hearing loss, can be a clinical feature of SLE and APS. Treating physicians should be aware of this devastating complication, especially when bilateral involvement occurs.

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