105 results
Search Results
2. Role of Lipid Rafts on LRP8 Signaling Triggered by Anti-β2-GPI Antibodies in Endothelial Cells.
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Riitano, Gloria, Capozzi, Antonella, Recalchi, Serena, Augusto, Mariaconcetta, Conti, Fabrizio, Misasi, Roberta, Garofalo, Tina, Sorice, Maurizio, and Manganelli, Valeria
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LIPID rafts ,ANTIPHOSPHOLIPID syndrome ,ENDOTHELIAL cells ,NITRIC-oxide synthases ,PHOSPHOLIPID antibodies ,IMMUNOGLOBULINS - Abstract
Antiphospholipid antibody syndrome is an autoimmune disease characterized by thrombosis and/or pregnancy morbidity in association with circulating antiphospholipid antibodies, mainly anti-β2 glycoprotein 1 antibodies (anti-β2-GPI antibodies). Previous studies demonstrated that the signaling pathway may involve lipid rafts, plasma membrane microdomains enriched in glycosphingolipid and cholesterol. In this study, we analyzed the signaling pathway of LRP8/ApoER2, a putative receptor of anti-β2-GPI antibodies, through lipid rafts in human endothelial cells. LRP8, Dab2 and endothelial nitric oxide synthase (e-NOS) phosphorylation were evaluated using Western blot, Nitric Oxide (NO) production with cytofluorimetric analysis, LRP8 enrichment in lipid rafts via sucrose gradient fractionation, and scanning confocal microscopy analysis of its association with ganglioside GM1 was also conducted. The analyses demonstrated that affinity-purified anti-β2-GPI antibodies induced LRP8 and Dab-2 phosphorylation, together with a significant decrease in e-NOS phosphorylation, with consequent decrease in NO intracellular production. These effects were almost completely prevented by Methyl-β-cyclodextrin (MβCD), indicating the involvement of lipid rafts. It was supported with the observation of LRP8 enrichment in lipid raft fractions and its association with ganglioside GM1, detected with scanning confocal microscopy. These findings demonstrate that LRP8 signaling triggered by anti-β2-GPI antibodies in endothelial cells occurs through lipid rafts. It represents a new task for valuable therapeutic approaches, such as raft-targeted therapy, including cyclodextrins and statins. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Criteria and Non-Criteria Antiphospholipid Antibodies in Antiphospholipid Syndrome: How Strong Are They Correlated?
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Caraiola, Simona, Voicu, Laura, Jurcut, Ciprian, Dima, Alina, Baicus, Cristian, Baicus, Anda, Cobilinschi, Claudia Oana, and Ionescu, Razvan Adrian
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PHOSPHOLIPID antibodies ,ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS - Abstract
The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-β2 glycoprotein I-aβ2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aβ2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool. [ABSTRACT FROM AUTHOR]
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- 2023
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4. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes.
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Nalli, C, Iodice, A, Andreoli, L, Lojacono, A, Motta, M, Fazzi, E, and Tincani, A
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SYSTEMIC lupus erythematosus ,AUTOIMMUNE diseases ,ANTIPHOSPHOLIPID syndrome ,THROMBOSIS ,IMMUNOGLOBULINS - Abstract
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that primarily affects women of childbearing-age. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thrombosis, often multiple, and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Recently, the long-term outcome of children born to patients with lupus and APS has become a major topic of interest both to patients and physicians. One of the major problems related to maternal disease is preterm delivery with all the consequences that this condition may bring. Prematurity may also be due to the presence of aPL; however, aPL do not generally display any thrombotic potential on neonates. Another complication may be neonatal lupus (NL), mediated by the presence of maternal antibodies (anti-Ro/SSA and anti-La/SSB). In addition, behaviour and neuropsychological outcomes have also been a matter of interest, but there are currently few data available. Beyond the biological influence of both maternal disease and autoimmune background, it is important to focus on the possible influence of maternal chronic illness on the neuropsychological development of her children. Whether aPL exposure could have a direct effect on brain development is still being debated. In children of mothers with APS, language delays have been noted and learning disabilities were described with a higher rate than the general age-school population. Several studies were performed on children born to lupus mothers: even if maternal lupus does not seem to impair intelligence levels, it may increase the occurrence of learning disabilities and particularly dyslexia in male children. To the best of our knowledge, no studies are available on the long-term outcome of children born to mothers with lupus or APS and particularly regarding the development of autoimmune diseases. Nevertheless, common experience of experts in the field is that these children do not show a significantly increased risk of displaying the same autoimmune disease as their mothers. The purpose of this paper is to answer the frequently asked questions of patients with lupus and APS who desire to become mothers, based on the little information available. [ABSTRACT FROM PUBLISHER]
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- 2014
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5. Hughes syndrome (the antiphospholipid syndrome): 25 years old.
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Edwards, C. J. and Hughes, G. R. V.
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ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases ,THROMBOSIS ,IMMUNOGLOBULINS ,MISCARRIAGE - Abstract
The antiphospholipid (Hughes) syndrome (APS) is a unique thrombotic disorder, causing both arterial and venous thrombosis, linked to the presence of antibodies directed against phospholipid–protein complexes. The first papers describing the syndrome were published in 1983 and, over the next two years, a series of publications described in detail the various clinical manifestations of the syndrome. Laboratory standardisation workshops were also set up and, in 1984, the first “world” symposium on APS was held. The international APS conferences have continued to grow in numbers and in stature. The APS has already had an impact in obstetrics, in medicine, in psychiatry, and in surgery. The approximate figure of 1 in 5 is a useful guide—1 in 5 of all young strokes, 1 in 5 recurrent miscarriages, 1 in 5 DVTs. More precise data will become available in the worlds of epilepsy, migraine, Alzheimer’s, and MS. The advent of newer “biologic” immunosuppressives such as rituximab may offer help in selected cases. Intravenous immunoglobulin has proved successful, especially in the emergency setting. [ABSTRACT FROM AUTHOR]
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- 2008
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6. From rheumatic fever to Libman–Sacks endocarditis: is there any possible pathogenetic link?
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Blank, M., Aron-Maor, A., and Shoenfeld, Y.
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RHEUMATIC fever ,ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,CENTRAL nervous system ,PHOSPHOLIPID antibodies ,AUTOIMMUNE diseases - Abstract
The heart lesions of rheumatic fever and the heart involvement in antiphospholipid syndrome (APS), have different clinical pictures. Yet, there are several common characteristics linking both diseases: 1) central nervous system (CNS) and heart involvement; 2) molecular mimicry between the a pathogen and the origin of the disease; 3) cross reacting antibodies between the pathogen and self molecules; 4) endothelial cell activation in the 'crime-area' i.e., the valves; 5) some of the patients with RF have circulating antiphospholipid antibodies, while APS may be associated with streptococcal infection; and 6) recently, a cross-reactivity between antibodies directed to the streptococcal M-protein and its synthetic derivative in rheumatic fever (RF) and antibodies derived from APS patients targeting the beta-2-glycoprotein-I (β2GPI) and a β2GPI related synthetic peptide. In the current paper, we summarize the possible links between the heart involvement in RF and APS. [ABSTRACT FROM AUTHOR]
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- 2005
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7. Anticardiolipin Antibodies and Ocular Disease.
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Lima Cabrita, Filipe Vieira and Stephen Foster, C.
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IMMUNOGLOBULINS ,EPIDEMIOLOGY ,AUTOIMMUNE diseases ,SYNDROMES ,INFECTIOUS disease transmission ,IMMUNOLOGY ,ANTIPHOSPHOLIPID syndrome ,DISEASES - Abstract
This paper reviews anticardiolipin antibodies and ocular disease. Its aim is to present the latest knowledge regarding the relationship between the two. It focuses mainly on ocular features and treatment, but also describes the epidemiology, main systemic features, immunology, and immunopathology of the antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]
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- 2005
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8. Antiphosphatidylserine antibodies and reproductive failure.
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Blank, M. and Shoenfeld, Y.
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AUTOIMMUNITY ,IMMUNOGLOBULINS ,ANTIGENS ,AUTOIMMUNE diseases ,SYSTEMIC lupus erythematosus ,VASCULAR diseases ,ANTIPHOSPHOLIPID syndrome ,BLOOD proteins - Abstract
Some cases of reproductive failure with autoimmune background are characterized by the involvement of autoantibodies. This occurs mainly in patients having systemic lupus erythematosus or antiphospholipid syndrome. The autoantibodies associated with reproductive failure include: a) antibodies which directly bind phospholipid (e.g., cardiolipin, phosphatidylserine, phosphatidylethanolamine); b) antiphospholipid Abs which bind the phospholipid via phospholipid-binding glycoproteins such as β2glycoprotein-I, annexin V and prothrombin; c) autoantibodies directed to laminin-I, actin, thromboplastin, the corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and mitochondrial antibodies of the M5 type. This paper will focus on the association of antiphosphatidylserine autoantibodies and reproductive failure. Future studies are likely to help to identify peptides resembling the epitope specificities associated with the specific clinical manifestations. [ABSTRACT FROM AUTHOR]
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- 2004
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9. Antiphospholipid (Hughes) syndrome: a review with update.
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Malaviya, Anand N.
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ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,SYPHILIS ,BLOOD coagulation disorders ,ANTICOAGULANTS - Abstract
Abstract This article reviews the evolution of the concept of Hughes syndrome starting with the discovery of beef heart extract-reactive antibodies in sera of patients with syphilis, presence of such antibodies in some normal individuals who went on to develop systemic lupus erythematosus (SLE), identification of the antigen as anionic phospholipids and some of the cofactors of the blood coagulation cascade, development of more refined techniques for detecting such antibodies and finally its implication in the causation of an acquired hypercoagulable state. The review then discusses the results of extensive international collaborative efforts of the major centres with interest and expertise in Hughes syndrome. It summarizes the recently enunciated classification criteria for this disease. The results and the implications of some of the recent seminal papers, especially on the frequency of different clinical manifestations in a large cohort of patients followed over long-periods, and recommendations for long-term high-intensity anticoagulation for the optimum management of this disease, are also discussed. [ABSTRACT FROM AUTHOR]
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- 2003
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10. A case of Waldenstroem's disease with a monoclonal IgM antiphospholipid antibody.
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von Landenberg, Philipp, Schölmerich, Jürgen, Andreesen, Reinhard, Vogelhuber, Martin, and Lackner, Karl J.
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IMMUNOGLOBULINS ,SYMPTOMS ,PHOSPHOLIPIDS ,BLOOD coagulation disorders ,ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases - Abstract
The antiphospholipid syndrome (APS) was described in 1983 as a clinical entity characterized by venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. The serological markers of APS are antiphospholipid antibodies (APLA) directed mainly against anionic phospholipids, usually cardiolipin but also phosphatidylserine. Some APLA exhibit lupus anticoagulant activity. Monoclonal gammopathy sometimes occurs with the presence of autoantibodies. In this paper, we describe a patient with the diagnosis of immunocytoma with an IgM, kappa paraprotein with apparent specificity against anionic phospholipids, and lupus anticoagulant activity, but no clinical signs of APS. We describe in this patient the presence of a high titer of monoclonal APLA, which does apparently not induce the clinical symptoms of APS. This might be indicative for the presence of pathogenic and nonpathogenic antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]
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- 2002
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11. Pathophysiology of Placenta in Antiphospholipid Syndrome.
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Bobircă, Anca, Dumitrache, Ana, Alexandru, Cristina, Florescu, Anca, Ciobotaru, George, Bobircă, Florin, Sima, Romina-Marina, Poalelungi, Cristian, Bojincă, Mihai, and Ancuța, Ioan
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PATHOLOGICAL physiology ,ANTIPHOSPHOLIPID syndrome ,PLACENTA ,RECURRENT miscarriage ,IMMUNOGLOBULINS - Abstract
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by clinical manifestations caused by arterial or venous thrombosis and pregnancy conditions such as recurrent miscarriage, fetal death, or premature birth in the presence of antiphospholipid antibodies. The obstetrical manifestations are strongly related to the placental alterations. The aim of this review is to summarize the latest data on pathophysiology of obstetrical APS, emphasizing the disturbance of the placentation process. Due to a lack of extravillous trophoblasts to properly reconstruct the spiral arteries, APS causes hypoxic or ischemic injury or high-speed blood flow that damages the placenta. This results in decreased or interrupted maternal blood flow to the placenta and a lack of nutrients for the fetus. Antiphospholipid antibodies can lower the proliferation and infiltration of the extravillous trophoblasts. The placental mal-perfusion causes the release of antiangiogenic substances such as soluble fms-like tyrosine kinase-1 and soluble endoglin. Placental growth factor and vascular endothelial growth factor (VEGF) may be sequestered by sFlt1 and blocked from binding to trophoblast and endothelial cell VEGF receptors, inhibiting their proangiogenic effects. Preeclampsia is the clinical result from a lack of angiogenic factors needed for endothelial vascular homeostasis due to an excess of sFlt1 in the maternal circulation. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies.
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Montaruli, B., De Luna, E., Erroi, L., Marchese, C., Mengozzi, G., Napoli, P., Nicolo’, C., Romito, A., Bertero, M. T., Sivera, P., and Migliardi, M.
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AUTOANTIBODIES ,CHEMILUMINESCENCE assay ,COMPARATIVE studies ,DIAGNOSTIC reagents & test kits ,FISHER exact test ,IMMUNOASSAY ,IMMUNOGLOBULINS ,PROBABILITY theory ,REFERENCE values ,RESEARCH evaluation ,STATISTICS ,EVALUATION research ,PREDICTIVE tests ,INTER-observer reliability ,DATA analysis software - Abstract
Introduction We evaluated analytical and clinical performances of IgG and IgM anticardiolipin ( aCL) antibodies and anti-β2-glycoprotein I (a-β2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer's cutoff values with different commercial methods. Methods We assayed aCL and a-β2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome ( APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases, using ELISA Inova Diagnostics; EliA Phadia Laboratory Systems; CliA Zenit- RA; and CliA Bio-Flash. Results Anticardiolipin and a-β2GpI IgG and IgM immunoassays showed good analytic performances with both 99th percentile and manufacturer's cutoff reference values. Our results showed fair to moderate agreement among assays. In-house cutoff values gave significantly better performances only for a-β2GpI IgG with all the immunoassays analyzed with the exception of Inova CliA Bio-Flash where we obtained the same performances with in-house and manufacturer's cutoffs. Conclusions By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low-positive, medium-/high-positive, and high-positive CliA IgG aCL and a-β2GpI ranges in order to help clinicians in the diagnosis and treatment of APS. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Defibrotide Inhibits Antiphospholipid Antibody–Mediated Neutrophil Extracellular Trap Formation and Venous Thrombosis.
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Ali, Ramadan A., Estes, Shanea K., Gandhi, Alex A., Yalavarthi, Srilakshmi, Hoy, Claire K., Shi, Hui, Zuo, Yu, Erkan, Doruk, and Knight, Jason S.
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IN vitro studies ,PROTEIN kinases ,IMMUNOGLOBULINS ,CYCLIC adenylic acid ,ANTIPHOSPHOLIPID syndrome ,ANIMAL experimentation ,VENOUS thrombosis ,NUCLEOTIDES ,DESCRIPTIVE statistics ,EXTRACELLULAR space ,MICE - Abstract
Objective: Defibrotide is a heterogenous mixture of polyanionic oligonucleotides currently approved for treatment of transplant‐associated venoocclusive disease. While defibrotide has a known role in limiting endothelial cell activation, some studies have also demonstrated anti‐leukocyte properties. In a recent study, we found that neutrophil extracellular traps (NETs) play a role in the thrombotic complications of antiphospholipid syndrome (APS). In the present study, we investigated the hypothesis that defibrotide might act to mitigate APS‐relevant NET formation in vitro and in mouse models. Methods: We used in vitro assays and a mouse model to determine the mechanisms by which defibrotide inhibits NET formation and venous thrombosis in APS. Results: At doses ranging from 1 to 10 μg/ml, defibrotide significantly suppressed NET formation from control neutrophils stimulated with IgG isolated from patients with APS. Defibrotide increased levels of intracellular cyclic AMP in neutrophils, and its suppressive effects on NET formation were mitigated by blocking adenosine A2A receptor or by inhibiting the cyclic AMP–dependent kinase protein kinase A. Defibrotide at doses ranging from 15 to 150 mg/kg/day inhibited NET formation and venous thrombosis in a model of antiphospholipid antibody–accelerated thrombosis—an effect that was reduced in adenosine A2A receptor–knockout mice. Conclusion: This study is the first to demonstrate mechanisms by which defibrotide counteracts neutrophil‐mediated thrombotic inflammation inherent to APS. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Anti-β2-GPI Antibodies Induce Endothelial Cell Expression of Tissue Factor by LRP6 Signal Transduction Pathway Involving Lipid Rafts.
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Riitano, Gloria, Capozzi, Antonella, Recalchi, Serena, Caissutti, Daniela, Longo, Agostina, Mattei, Vincenzo, Conti, Fabrizio, Misasi, Roberta, Garofalo, Tina, Sorice, Maurizio, and Manganelli, Valeria
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LIPID rafts ,ENDOTHELIAL cells ,CELLULAR signal transduction ,IMMUNOGLOBULINS ,MEMBRANE lipids ,WNT signal transduction - Abstract
In this study we analyzed whether anti-β2-GPI antibodies from patients with APS induce the endothelial cell expression of Tissue Factor (TF) by a LRP6 signal transduction pathway involving lipid rafts. HUVEC were stimulated with affinity purified anti-β2-GPI antibodies. Both LRP6 and β-catenin phosphorylation, as well as TF expression, were evaluated by western blot. Results demonstrated that triggering with affinity purified anti-β2-GPI antibodies induced LRP6 phosphorylation with consequent β-catenin activation, leading to TF expression on the cell surface. Interestingly, the lipid rafts affecting agent methyl-β-cyclodextrin as well as the LRP6 inhibitor Dickkopf 1 (DKK1) partially reduced the anti-β2-GPI antibodies effect, indicating that the anti-β2-GPI effects on TF expression may depend on a signalling transduction pathway involving both lipid rafts and LRP6. An interaction between β2-GPI, LRP6 and PAR-2 within these microdomains was demonstrated by gradient fractionation and coimmunoprecipitation experiments. Thus, anti-β2-GPI antibodies react with their target antigen likely associated to LRP6 and PAR-2 within plasma membrane lipid rafts of the endothelial cell. Anti-β2-GPI binding triggers β-catenin phosphorylation, leading to a procoagulant phenotype characterized by TF expression. These findings deal with a novel signal transduction pathway which provides new insight in the APS pathogenesis, improving the knowledge of valuable therapeutic target(s). [ABSTRACT FROM AUTHOR]
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- 2022
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15. Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies.
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Ali, Omar Hasan, Bomze, David, Risch, Lorenz, Brugger, Silvio D, Paprotny, Matthias, Weber, Myriam, Thiel, Sarah, Kern, Lukas, Albrich, Werner C, Kohler, Philipp, Kahlert, Christian R, Vernazza, Pietro, Bühler, Philipp K, Schüpbach, Reto A, Gómez-Mejia, Alejandro, Popa, Alexandra M, Bergthaler, Andreas, Penninger, Josef M, and Flatz, Lukas
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AUTOANTIBODIES ,DIAGNOSTIC reagents & test kits ,RESPIRATORY mucosa ,COVID-19 ,IMMUNOGLOBULINS ,ANTIPHOSPHOLIPID syndrome ,RETROSPECTIVE studies ,TERTIARY care ,COMPARATIVE studies ,SEVERITY of illness index ,MEDICAL records ,DESCRIPTIVE statistics ,STATISTICAL correlation ,VIRAL antibodies ,DATA analysis software ,LONGITUDINAL method - Abstract
Background Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A–mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL). Methods In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020. Results Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P =.01; scCOVID, P <.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P <.001), anticardiolipin IgM (sdCOVID, P =.003; scCOVID, P <.001), and anti–beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P <.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. Conclusions Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Does seronegative antiphospholipid syndrome really exist?
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Cervera, Ricard, Conti, Fabrizio, Doria, Andrea, Iaccarino, Luca, and Valesini, Guido
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ANTIPHOSPHOLIPID syndrome , *CARDIOLIPIN , *GLYCOPROTEINS , *IMMUNOGLOBULINS , *DISEASE complications , *THROMBOSIS , *DIAGNOSIS - Abstract
Abstract: The diagnosis of seronegative (SN-) antiphospholipid syndrome (APS) has been suggested for patients with clinical manifestations indicative of APS but with persistently negative results in the commonly used assays to detect anti-cardiolipin (aCL) antibodies, anti-β2 Glycoprotein I antibodies (aβ2GPI), and lupus anticoagulant (LA). To date the best management of these patients is still unclear. New emerging anti-phospholipid (aPL) assays could improve our ability in diagnosing APS. However, the availability of aPL assays in routine laboratory practice is limited. In fact, even aβ2GPI is routinely tested in only a small number of laboratories, and other aPL, such as anti-prothrombin or anti-annexin antibodies, in only a few research laboratories. On the other hand transient or false negative aPL assay and other genetic or acquired pro-thrombotic conditions can further complicate this issue. This paper is focused on the arguments for and against the diagnosis of SN-APS and is aimed to help the clinician when approaching a patient with clinical manifestations consistent with APS diagnosis but with negative aPL using the commonly available tests. [Copyright &y& Elsevier]
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- 2012
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17. Mecanismos patogénicos de los anticuerpos antifosfolípidos.
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Núñez-Álvarez, Carlos A. and Cabiedes, Javier
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ANTIPHOSPHOLIPID syndrome , *AUTOIMMUNE diseases , *IMMUNOGLOBULINS , *PHOSPHOLIPIDS , *SYSTEMIC lupus erythematosus , *GLYCOPROTEINS - Abstract
The antiphospolipid syndrome (APS) is an autoimmune disease characterized by recurrent fetal loss, thrombotic events (arterial or venous) and hemocytopenic disorders associated to high titers of circulating aPL Two variants of the APS have been described. Primary APS is a clinical entity without evidence of any other autoimmune disease and secondary APS is a clinical disorder mainly associated with Systemic Lupus Erithematosus (SLE). aPL are a widely group of immunoglobulins directed against different components or proteins factors. In 1990 three groups of researchers identified that β2GP-I is the mainly antigenic target of aPL in APS patients. There are evidences that show that more than one pathogenic mechanism is involved in the development of the APS. The best documented clinical manifestations associated with the APS are recurrent fetal loss and thrombotic disorders. The latter is based on observations in vivo in animal models and in vitro on the effects caused by β2GP-I antibodies from patients with APS or from animals which cause experimental APS. The objective of the present paper is to show the pathogenic mechanisms that participate in the development of the APS. We also presented evidence that shows that β2GP-I induces pro-inflammatory, pro-adhesive and pro-coagulant disorder. [ABSTRACT FROM AUTHOR]
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- 2011
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18. Antiprothombin antibodies and the diagnosis of antiphospholipid syndrome
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Amengual, Olga, Atsumi, Tatsuya, and Koike, Takao
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ANTIPHOSPHOLIPID syndrome , *AUTOIMMUNE diseases , *IMMUNOGLOBULINS , *GLOBULINS - Abstract
The preliminary classification criteria for definite antiphospholipid syndrome (APS) include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) as laboratory criteria. However, antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies comprising also antibodies against phospholipid-binding proteins or their complexes with phospholipids. Prothrombin is one of the antigen recognized by aPL. In the last decade, there has been increasing interest in antibodies against prothrombin alone and those against phosphatidylserine–prothrombin complex. The latter, phosphatidylserine-dependent antiprothrombin antibodies (aPT), have been closely associated with APS and LA. In this paper, we review the properties of antiprothrombin antibodies. [Copyright &y& Elsevier]
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- 2004
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19. Antiphospholipid Syndrome in Greece: Clinical and Immunological Study and Review of the Literature.
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Boura, Panagiota, Tselios, Konstantinos, Skendros, Panagiotis, and Kountouras, Jannis
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ANTIPHOSPHOLIPID syndrome , *AUTOIMMUNE diseases , *VASCULAR diseases , *CARDIOLOGY , *IMMUNOGLOBULINS , *IMMUNOLOGY , *EPIDEMIOLOGY - Abstract
The aim of this paper is to analyze the epidemiologic, clinical, and immunologic characteristics of the antiphospholipid syndrome (APS), primary or secondary, in autoimmune patients from Northern Greece. Sixty-seven patients with APS were included (9 men, 13.4%, and 58 women, 86.6%). Fifty-two (77.6%) patients had secondary APS and 15 had primary APS (22.4%). The mean age was 46.0 ± 15.4 years and the mean follow-up period was 62.7 ± 15.0 months. Medical records were retrospectively analyzed from January 1994 until December 2001, according to a preestablished protocol. Eight patients (11.9%) had arterial thrombosis, 12 (17.9%) had vein thrombosis, 12 (17.9%) had thrombocytopenia, 20 (29.8%) had neurologic disorders, and 51.6% of the women in reproductive age had, at least 2 fetal losses (higher frequency in primary APS). Thirty-six patients (53.7%) had increased levels of both immunoglobulin G (Ige) and IgM anticardiolipin antibodies (ACA), 19 (28.4%) had IgG ACA only, and 12 (17.7%) had IgM ACA only. Antinuclear antibodies (ANA) were detected in 46 (68.6%) patients, and antineutrophil cytoplasmic antibodies (ANCA) in 29 (43.3%). All patients were prophylactically treated with aspirin (50–100 mg/day) and low-molecular-weight heparin and/or intravenous immunoglobulins-IVIGs occasionally (pregnant women). The findings of this study are, generally, similar to those described by others. Miscarriages seem to be more frequent in women with primary APS (p<0.05), compared to other studies. Differences between these findings and those described by others concerning epidemiologic, clinical, or immunologic data are discussed. [ABSTRACT FROM AUTHOR]
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- 2004
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20. Specific domain V reduction of beta-2-glycoprotein I induces protein flexibility and alters pathogenic antibody binding.
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Buchholz, Ina, McDonnell, Thomas, Nestler, Peter, Tharad, Sudarat, Kulke, Martin, Radziszewska, Anna, Ripoll, Vera M., Schmidt, Frank, Hammer, Elke, Toca-Herrera, Jose L., Rahman, Anisur, and Delcea, Mihaela
- Subjects
GLYCOPROTEINS ,IMMUNOGLOBULINS ,AUTOIMMUNE diseases ,ANTIPHOSPHOLIPID syndrome ,PROTEIN conformation - Abstract
Beta-2-glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder antiphospholipid syndrome (APS). β2GPI exists mainly in closed or open conformations and comprises of 11 disulfides distributed across five domains. The terminal Cys288/Cys326 disulfide bond at domain V has been associated with different cysteine redox states. The role of this disulfide bond in conformational dynamics of this protein has not been investigated so far. Here, we report on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine; TCEP) of β2GPI. Specific reduction was demonstrated by Western blot and mass spectrometry analyses confirming majority targeting to the fifth domain of β2GPI. Atomic force microscopy images suggested that reduced β2GPI shows a slightly higher proportion of open conformation and is more flexible compared to the untreated protein as confirmed by modelling studies. We have determined a strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI as demonstrated by ELISA. Our study is relevant for understanding the effect of β2GPI reduction on the protein structure and its implications for antibody binding in APS patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
21. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Obstetric Antiphospholipid Syndrome.
- Author
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de Jesús, Guilherme R, Benson, Ashley E, Chighizola, Cecilia B, Sciascia, Savino, and Branch, David W
- Subjects
PHOSPHOLIPID antibodies ,TASK forces ,ANTIPHOSPHOLIPID syndrome ,CONFERENCES & conventions ,EVIDENCE-based medicine ,IMMUNOGLOBULINS - Abstract
Obstetric antiphospholipid syndrome (APS) remains a clinical challenge for practitioners, with several controversial points that have not been answered so far. This Obstetric APS Task Force met on the 16th International Congress on Antiphospholipid Antibodies in Manchester, England, to discuss about treatment, diagnostic and clinical aspects of the disease. This report will address evidence-based medicine related to obstetric APS, including limitations on our current management, the relationship between antibodies against domain 1 of β2GPI and obstetric morbidity, hydroxychloroquine use in patients with obstetric APS and factors associated with thrombosis after obstetric APS. Finally, future directions for better understanding this complex condition are also reported by the Task Force coordinators. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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22. Antiphospholipid antibody levels in early systemic lupus erythematosus: are they associated with subsequent mortality and vascular events?
- Author
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Pericleous, Charis, D'Souza, Amrita, McDonnell, Thomas, Ripoll, Vera M, Leach, Oliver, Isenberg, David, Giles, Ian, and Rahman, Anisur
- Subjects
ANTICOAGULANTS ,ANTIPHOSPHOLIPID syndrome ,AUTOANTIBODIES ,BLOOD collection ,BLOOD vessels ,CARDIOVASCULAR agents ,CARDIOVASCULAR diseases ,COMPARATIVE studies ,ENZYME-linked immunosorbent assay ,GLYCOPROTEINS ,IMMUNOGLOBULINS ,MEDICAL records ,PHOSPHOLIPIDS ,SYSTEMIC lupus erythematosus ,THROMBOSIS ,DNA-binding proteins ,DESCRIPTIVE statistics ,KAPLAN-Meier estimator ,ACQUISITION of data methodology ,CHEMICAL inhibitors - Abstract
Objectives aPL are present in between 20 and 30% of patients with SLE. They can cause vascular events (VE) or pregnancy morbidity. aCL and anti-beta-2-glycoprotein I (anti-β2GPI) are measured in clinical practice. Domain I (DI) of β2GPI is the main site for aPL binding. We investigated the prevalence of IgG anti-DI, aCL and anti-β2GPI antibodies in early SLE and their association with mortality and development of VE. Methods Samples from 501 patients with SLE that had been obtained and stored early during their disease were tested for IgG anti-DI, aCL and anti-β2GPI antibodies by ELISA. LA status and history of VE were obtained by reviewing medical records. Kaplan–Meier analysis was used to investigate mortality and occurrence of VE, comparing groups with and without aPL in early disease. Results Of 501 patients, 190 (38%) had at least one of these aPL, of whom 112 had anti-DI alone. Of 276 patients with complete vascular history, 83 had experienced VE. The 39 patients who were double or triple-ELISA-positive for any combination of the three aPL were more likely to have or develop lupus anticoagulant (P <0.0001) than those who were single-ELISA-positive or negative. In Kaplan–Meier analysis, they showed a trend towards developing more VE (P = 0.06). Conclusion IgG anti-DI antibodies were present in early serum samples from 29% of patients and were more common than IgG aCL or anti-β2GPI. There was some evidence suggesting that double or triple-ELISA-positivity for these antibodies identified a group with worse outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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23. Extended persistence of antiphospholipid antibodies beyond the 12‐week time interval: Association with baseline antiphospholipid antibodies titres.
- Author
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Devignes, Jean, Smaïl‐Tabbone, Malika, Hervé, Alex, Cagninacci, Geoffroy, Devignes, Marie‐Dominique, Lecompte, Thomas, Zuily, Stéphane, and Wahl, Denis
- Subjects
ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,TIME ,RETROSPECTIVE studies - Abstract
Introduction: The confirmation time interval for the presence of antiphospholipid antibodies (aPL) has been extended to 12 weeks as epiphenomenal antibodies may disappear after 6 weeks. Our aim was to analyse extended persistence of aPL positivity beyond the 12‐week interval. Methods: We retrospectively analysed our database of 23 856 aPL test samples collected between 2005 and 2017 from 17 367 consecutive patients. Two groups of patients were identified among aPL‐positive patients, confirmed at 12 weeks: with or without extended persistence beyond confirmatory testing. Percentages of extended persistence are given according to the initial aPL positivity profiles, and baseline laboratory variables are compared between the two groups. Results: Three hundred and twenty‐seven patients confirmed aPL‐positive had subsequent testing. The vast majority of them displayed extended persistence in the long term: 89.6% and up to 97.9% for patients with initial triple positivity. In extended persistent positive patients, there were more LA‐positive initial samples, and baseline LA test values and IgG aCL titres were higher than in nonpersistent positive patients. Conclusion: Data from a large database of an aPL referral laboratory showed that the time interval of 12 weeks defining persistence of aPL positivity was appropriate for the majority of patients. Furthermore, we found baseline features associated with extended persistence. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. The antiphospholipid syndrome finally fathomed?
- Author
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de Groot, Philip G.
- Subjects
- *
ANTIPHOSPHOLIPID syndrome , *THROMBOSIS , *ENDOTHELIUM , *ENDOTHELIAL cells , *IMMUNOGLOBULINS - Abstract
The article discusses a research paper on antiphospholipid (APS) syndrome. It references the study "Antiphospholipid Antibodies Induce Thrombosis by PP2A Activation Via apoER2-Dab2-SHC1 Complex Formation in Endothelium," by A. Sacharidou et al., published within the issue. It tackles the characterization of APS syndrome and the significant role of endothelial cells in the thrombotic risk induced by anti-β2 glycoprotein I antibodies.
- Published
- 2018
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25. ANTIPHOSPHOLIPIDIC ANTIBODIES IN SARS-COV2 INFECTION: STILL A LOT TO LEARN.
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Jurcu, Ciprian and Sciascia, Savino
- Subjects
ANTIPHOSPHOLIPID syndrome ,SARS-CoV-2 ,COVID-19 ,IMMUNOGLOBULINS - Abstract
Lupus Anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results? A review of (8) the published studies by Gkrouzman et al reported an overall aPLs positivity as high as 58% in COVID-19 patients, with the majority of the patients being positive for LA. Critically, the question of whether transient aPLs positivity found in critically ill patients or during times of SARS-CoV2 infection may have a pathogenic role for the development of incident thromboses and lead to antiphospholipid syndrome (APS) has been poorly understood. [Extracted from the article]
- Published
- 2021
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26. Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies.
- Author
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Songwang Hou, Ke Ke, Ming Zhao, Fölsch, Heike, Mills, Joan Cook, and Ramsey-Goldman, Rosalind
- Subjects
ENDOSOMES ,PHOSPHATIDYLETHANOLAMINES ,IMMUNOGLOBULINS ,ANTIPHOSPHOLIPID syndrome ,BINDING agents ,GENETICS - Abstract
Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a normal resting cell, and the mechanism by which circulating anti-PE antibodies access cellular PE remains unknown. The studies presented here were conducted with synthetic PE-binding agents, plasma samples from patients with anti-PE autoimmunity, and purified anti-PE antibodies. The results suggest that the cellular vulnerability to anti-PE antibodies may be mediated by the binding of PE molecules in the membrane of the early endosome. Endosomal PE binding led to functional changes in endothelial cells, including declines in proliferation and increases in the production of reactive oxygen species, as well as the expression of inflammatory molecules. Collectively, our findings provide insight into the etiology of anti-PE autoimmunity and, because endosomes are of central importance in almost all types of cells, could have important implications for a wide range of biological processes. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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27. The Role of TLR4 on B Cell Activation and Anti-2GPI Antibody Production in the Antiphospholipid Syndrome.
- Author
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Cheng, Si, Wang, Haibo, and Zhou, Hong
- Subjects
- *
TOLL-like receptors , *B cells , *ANTIPHOSPHOLIPID syndrome , *GLUCOSE 6-phosphatase , *IMMUNOGLOBULINS , *PATIENTS , *ANTIPHOSPHOLIPID syndrome treatment , *ANTIGENS , *AUTOANTIBODIES , *CELL differentiation , *CELL receptors , *CELLULAR signal transduction , *DRUG therapy , *CYTOKINES , *GLYCOPROTEINS , *IMMUNITY , *IMMUNOLOGY technique , *IMMUNOTHERAPY , *T cells , *TUMOR necrosis factors , *ANTIBODY formation - Abstract
High titer of anti-β2-glycoprotein I antibodies (anti-β2GPI Ab) plays a pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused on the pathological mechanism in APS; however, little attention is paid to the immune mechanism of production of anti-β2GPI antibodies in APS. Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI. However, TLR4 provides a third signal for B cell activation and then promotes B cells better receiving signals from both B cell antigen receptor (BCR) and CD40, thus promoting B cell activation, surface molecules expression, anti-β2GPI Ab production, and cytokines secretion and making B cell functioning like an antigen presenting cell (APC). At the same time, TLR4 also promotes B cells producing antibodies by upregulating the expression of B-cell activating factor (BAFF). In this paper, we aim to review the functions of TLR4 in B cell immune response and antibody production in autoimmune disease APS and try to find a new way for the prevention and treatment of APS. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. Oral.
- Subjects
ANTIPHOSPHOLIPID syndrome ,BIOMARKERS ,BIOPSY ,BLOOD diseases ,CHROMOSOME abnormalities ,MENTAL depression ,EXPERIENCE ,FERTILIZATION in vitro ,FETAL ultrasonic imaging ,IMMUNOGLOBULINS ,EVALUATION of medical care ,GENETIC mutation ,PREGNANCY ,SPERMATOZOA ,VITAMIN D ,GENOMICS ,RECURRENT miscarriage ,ENOXAPARIN - Published
- 2017
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29. Antiphospholipid Syndrome.
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Chinoy, Hector, Espinosa, Gerard, and Rahman, Anisur
- Subjects
ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,THROMBOCYTOPENIA ,AUTOIMMUNE hemolytic anemia ,AUTOIMMUNE diseases - Abstract
The article offers information on a study which examined whether patients with antiphospholipid antibodies (aPL) and thrombocytopenia and/or autoimmune hemolytic anemia (AIHA) presented with clinical criteria of antiphopholipid syndrome (APS) during follow-up. In view of the presence of lupus anticoagulant (LAC) in patients with thrombocytopenia, a subset of patients with high risk for developing thrombosis during follow-up was identified. The results provided a rationale for studies to evaluate the need for anticoagulant in these patients.
- Published
- 2011
30. Antiphospholipid Syndrome.
- Subjects
RITUXIMAB ,ANTINEOPLASTIC agents ,MONOCLONAL antibodies ,ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases ,ANTICOAGULANTS ,IMMUNOGLOBULINS - Abstract
The article presents the findings of a study on the efficacy of rituximab in the treatment of resistant antiphospholipid syndrome (APS) and its variant, catastrophic APS. Some of the most common therapies used include oral anticoagulants, corticosteroids, plasma exchange, intravenous immunoglobulins and cyclophosphamide. The administration of rituximab, an anti-CD20 monoclonal antibody, and its effect on the patients are discussed.
- Published
- 2006
31. Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes.
- Author
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Yuichiro Fujieda, Olga Amengual, Masaki Matsumoto, Kimiko Kuroki, Hidehisa Takahashi, Michihito Kono, Takashi Kurita, Kotaro Otomo, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Katsumi Maenaka, Shigetsugu Hatakeyama, Keiichi I. Nakayama, and Tatsuya Atsumi
- Subjects
ANTIPHOSPHOLIPID syndrome ,CELL culture ,CHI-squared test ,ENZYME-linked immunosorbent assay ,FISHER exact test ,FLOW cytometry ,GENE expression ,IMMUNOGLOBULINS ,LIQUID chromatography ,MASS spectrometry ,MEMBRANE proteins ,MONOCLONAL antibodies ,POLYMERASE chain reaction ,RESEARCH funding ,RNA ,THROMBOSIS ,PROTEOMICS ,DATA analysis software ,DESCRIPTIVE statistics ,PROTHROMBIN time ,IN vitro studies ,DISEASE complications - Abstract
Objective. Phosphatidylserine-dependent, also called aPS-PT, recognizes the phosphati dylserine-prothrombin complex, which is associated with APS. We have previously reported that aPS-PT induces tissue factor (TF) expression on monocytes through the p38 mitogen-activated protein kinase pathway. However, the cell surface interaction between prothrombin and aPS-PT, which is involved in the activation of cell-signalling pathways, has remained unknown. The objective of this study was to identify membrane proteins involved in the binding of prothrombin and aPS-PT to monocyte surfaces as well as the induction of TF expression. Methods. RAW264.7 cells with FLAG-tagged prothrombin were incubated and separated using affinity chromatography with anti-FLAG antibody-conjugated Sepharose beads. Immunopurified proteins were then analysed by an online nano-liquid chromatography-tandem mass spectrometry. The binding between prothrombin and the identified protein, ribophorin II (RPN2), was analysed by ELISA and surface plasmon resonance. To elucidate the role of RPN2 in TF expression, the TF mRNA level in RAW264.7 cells treated with RPN2 small interfering RNA was determined by quantitative real-time PCR (qPCR). Results. RPN2 was identified as a candidate molecule involved in the binding of prothrombin to the cell surface. The binding between prothrombin and RPN2 was confirmed by ELISA and surface plasmon resonance. RAW264.7 cells treated with RPN2 small interfering RNA showed significant reduction of the TF expression mediated by prothrombin and a mouse monoclonal aPS-PT. Conclusion. We identified that RPN2 is one of the prothrombin-binding proteins on monocyte surfaces, suggesting that RPN2 is involved in the pathophysiology of thrombosis in patients with APS. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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32. Measuring IgA Anti-β2-Glycoprotein I and IgG/IgA Anti-Domain I Antibodies Adds Value to Current Serological Assays for the Antiphospholipid Syndrome.
- Author
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Pericleous, Charis, Ferreira, Isabel, Borghi, Orietta, Pregnolato, Francesca, McDonnell, Thomas, Garza-Garcia, Acely, Driscoll, Paul, Pierangeli, Silvia, Isenberg, David, Ioannou, Yiannis, Giles, Ian, Meroni, Pier Luigi, and Rahman, Anisur
- Subjects
GLYCOPROTEINS ,IMMUNOGLOBULINS ,CARDIOLIPIN ,ANTIPHOSPHOLIPID syndrome ,OBSTETRICS ,PATIENTS - Abstract
Introduction: Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and β
2 -glycoprotein I (aβ2 GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of β2 GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, β2 GPI and DI in APS. Methods: Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, aβ2 GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. Results: All assays displayed good specificity for APS; IgG aCL and IgG aβ2 GPI assays however, had the highest sensitivity. Testing positive for IgA aβ2 GPI resulted in a higher hazard ratio for APS compared to IgM aβ2 GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or aβ2 GPI, the presence of aDI raised the hazard ratio for APS by 3–5 fold. IgG aCL, aβ2 GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. Conclusion: Measuring IgG aDI and IgA aβ2 GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
33. A Clinical Approach for Defining the Threshold between Low and Medium Anti-Cardiolipin Antibody Levels for QUANTA Flash Assays.
- Author
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Lakos, Gabriella, Bentow, Chelsea, and Mahler, Michael
- Subjects
CARDIOLIPIN ,IMMUNOGLOBULINS ,ANTIPHOSPHOLIPID syndrome ,CHEMILUMINESCENCE ,SYSTEMIC lupus erythematosus ,ENZYME-linked immunosorbent assay - Abstract
The threshold between low and medium antibody levels for anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) for the diagnosis of antiphospholipid syndrome (APS) remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for aCL antibody methods based on a clinical approach, and utilize it to establish the clinically-relevant low/medium threshold for QUANTA Flash aCL chemiluminescent immunoassay (CIA) results. The study included 288 samples from patients with primary APS (n = 70), secondary APS (n = 42), suspected APS (n = 36), systemic lupus erythematosus (SLE) without APS (n = 96) and other connective tissue diseases (n = 44). All samples were tested for IgG and IgM aCL antibodies with QUANTA Flash CIA, along with traditional enzyme-linked immunosorbent assays (ELISAs) (QUANTA Lite). The assay specific low/medium threshold for QUANTA Flash aCL IgG and IgM assays (i.e., the equivalent of 40 GPL and MPL units) was established as 95 and 31 chemiluminescent units (CU), respectively, based on clinical performance and comparison to QUANTA Lite ELISAs. Agreement between CIA and ELISA assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen's kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for IgM aCL results. This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 CU, respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results. This study can serve as a model for labs wishing to establish the appropriate low/medium aPL antibody threshold when implementing new aPL antibody assays. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
34. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review.
- Author
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Rodríguez-García, Veronica, Ioannou, Yiannis, Fernández-Nebro, Antonio, Isenberg, David A., and Giles, Ian P.
- Subjects
ANTIPHOSPHOLIPID syndrome ,CHI-squared test ,ENZYME-linked immunosorbent assay ,IMMUNOGLOBULINS ,MEDICAL information storage & retrieval systems ,MEDLINE ,META-analysis ,ONLINE information services ,RESEARCH funding ,SYSTEMATIC reviews ,DIAGNOSIS - Abstract
Objective. To systematically review and establish the prevalence of antibody positivity in assays not currently included in the APS classification criteria to detect antibodies directed against other phospho-lipids (PLs), PL binding proteins, coagulation factors and a mechanistic test for resistance of Annexin A5 (AnxA5) anticoagulant activity in APS and control populations. Methods. We searched PubMed and EMBASE using the key words APS, antiphospholipid antibodies, non-criteria, new assays, IgA anticardiolipin antibodies, lupus anticoagulant, anti-Domain I, IgA anti-b2-glycoprotein I antibodies, antiphosphatidylserine, anti-phosphatidylethanolamine, anti-phosphatidic acid, antiprothrombin, antiphosphatidylserine-prothtombin, anti-vimentin/cardiolipin complex and Annexin A5 resistance. Studies that met inclusion criteria to describe prevalence of non-criteria aPLs in APS patients (n>10), disease and healthy control subjects were systematically examined. Results. We selected 16 retrospective studies of 1404 APS patients, 1839 disease control and 797 healthy controls. The highest prevalence of non-criteria aPLs in the largest number of patients with APS was found in IgA anti-β2GPI studies (129/229, 56.3%), AnxA5R (87/163, 53.4%) and IgG anti-Domain I (241/548, 44.0%). Conclusion. Our finding of a significantly high prevalence of all non-criteria aPLs studied in patients with APS compared with controls was tempered by wide variation in sample size, retrospective collection, assay methodology and different determination of positivity. Therefore, prospective studies of sufficient size and appropriate methodology are required to evaluate the significance of these assays and their utility in the management of patients with APS. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
35. Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies.
- Author
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Maity, Arindam, Macaubas, Claudia, Mellins, Elizabeth, and Astakhova, Kira
- Subjects
PHOSPHOLIPID synthesis ,AUTOIMMUNE disease diagnosis ,IMMUNOGLOBULINS ,COPPER catalysts ,ANTIGENS - Abstract
Copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin. The resulting phospholipid-protein conjugates show high binding affinity and specificity for the autoimmune antibodies against autoimmune complexes. Thus, the development of this work might become a milestone in further diagnostics and therapy of autoimmune diseases that involve the production of autoantibodies against the aforementioned phospholipids and proteins, such as antiphospholipid syndrome and systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
36. Autoantibody response and pregnancy-related pathology induced by combined LPS and tetanus toxoid hyperimmunization in BALB/c and C57BL/6 mice.
- Author
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Petrušić, Vladimir, Todorović, Nevena, Živković, Irena, Dimitrijević, Rajna, Muhandes, Lina, Rajnpreht, Irena, and Dimitrijević, Ljiljana
- Subjects
GLYCOPROTEINS ,ANTIPHOSPHOLIPID syndrome ,FERTILITY ,MOLECULAR mimicry ,IMMUNOGLOBULINS ,AUTOIMMUNITY - Abstract
Recent data concerning antiphospholipid syndrome (APS) induction have shown that β
2 -glycoprotein I (β2 GPI) binds lipopolysaccharide (LPS), which results in conformational changes, exposition of a cryptic epitope and possible pathological anti-β2 GPI antibody production. In order to investigate the effects of LPS on the induction of APS-related pathology, we performed hyperimmunization of BALB/c and C57BL/6 mice with LPS, alone or in combination with tetanus toxoid (TTd), a protein structurally similar to β2 GPI. We report that, although high affinity pathological anti-β2 GPI antibodies were produced in all groups of animals, the reproductive pathology was recorded only in mice that received both LPS and TTd, implying on the important roles of both infections and molecular mimicry in APS pathogenesis. Moreover, APS-related reproductive pathology was more pronounced in BALB/c (lowered fertility and fecundity) than C57BL/6 mice (lowered fecundity), which correlated well with the disruption in natural antibody network observed in BALB/c mouse strain. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
37. An A1-A1 mutant with improved binding and inhibition of β2 GPI/antibody complexes in antiphospholipid syndrome.
- Author
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Kolyada, Alexey, Karageorgos, Ioannis, Mahlawat, Pardeep, and Beglova, Natalia
- Subjects
ANTIPHOSPHOLIPID syndrome ,GENETIC mutation ,ENZYME inhibitors ,IMMUNOGLOBULINS ,CARDIOLIPIN ,LOW density lipoproteins ,PATIENTS - Abstract
β2 glycoprotein I (β2 GPI) is the most common antigen for autoimmune antibodies in antiphospholipid syndrome ( APS). Thrombosis is a clinical feature of APS. We created a molecule (A1-A1) that consists of two identical β2 GPI-binding modules from ApoE receptor 2 (Apo ER2). A1-A1 binds to β2 GPI/antibody complexes, preventing their association with Apo ER2 and anionic phospholipids, and reducing thrombus size in the mouse model of APS. Here, we describe a mutant of A1-A1 (mA1-A1 ND) with improved affinity for β2 GPI. mA1-A1 ND inhibits the binding of β2 GPI to cardiolipin in the presence of anti-β2 GPI antibodies, and inhibits the binding to phospholipids in plasma samples of APS patients, affecting the clotting time. Reduction of the clotting time demonstrates the presence of soluble β2 GPI/antibody complexes in patients' plasma. These complexes either already exist in patients' plasma or form rapidly in the proximity to phospholipids. All members of the low-density lipoprotein receptor family bind β2 GPI. Modeling studies of A1 in a complex with domain V of β2 GPI (β2 GPI- DV) revealed two possible modes of interaction of a ligand-binding module from lipoprotein receptors with β2 GPI- DV. In both orientations, the ligand-binding module interferes with binding of β2 GPI to anionic phospholipids; however, it interacts with two different but overlapping sets of lysine residues in β2 GPI- DV, depending on the orientation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
38. Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome.
- Author
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Khogeer, H, Alfattani, A, Al Kaff, M, Al shehri, T, Khojah, O, and Owaidah, T
- Subjects
ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,SYNDROMES ,AUTOIMMUNE diseases ,MEDICAL care - Abstract
The article focuses on study that assess the diagnostic value of antiphospholipid syndrome (aPS) antibodies and compare their utility to that of other aPL antibodies. Topics discussed prospective observational study, diagnostic value of aPS versus other aPL antibodies and independent association between aPS and primary APS.
- Published
- 2015
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39. Recurrent episodes of hemorrhagic alveolitis in relapsing catastrophic antiphospholipid syndrome: the same side of the dark moon.
- Author
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Pieralli, Filippo, Grazzini, Maddalena, Vannucchi, Vieri, Mancini, Antonio, Cammelli, Daniele, and Nozzoli, Carlo
- Subjects
ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,THROMBOTIC thrombocytopenic purpura ,MORTALITY ,ALVEOLITIS ,DYSPNEA - Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a rare variant of antiphospholipid syndrome characterized by widespread thrombotic microangiopathy and multiorgan failure. Clinically, CAPS signs and symptoms can mimic vasculitis of systemic lupus erythematosus, disseminated intravascular coagulation, and thrombotic thrombocytopenic purpura. CAPS is burdened by high mortality, nearly 50 % in most series. However, patients surviving the acute phase rarely suffer of CAPS relapses. Moreover, concomitant pulmonary hemorrhagic alveolitis is a very rare complication warranting an ominous prognosis. Only few reports of relapsing CAPS are described in literature, and pathogenetic mechanisms are poorly understood and the optimal treatment is yet unknown. We report a case of a young man suffering from multiple relapses of CAPS and recurrent hemorrhagic pulmonary alveolitis refractory to aggressive combination treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
40. Catastrophic antiphospholipid syndrome: a clinical review.
- Author
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Nayer, Ali and Ortega, Luis M.
- Subjects
ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases ,PHOSPHOLIPIDS ,IMMUNOGLOBULINS ,BLOOD proteins - Abstract
Context: Catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening autoimmune disease characterized by disseminated intravascular thrombosis resulting in multiorgan failure. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: CAPS is due to antiphospholipid antibodies directed against a heterogeneous group of proteins that are associated with phospholipids. These autoantibodies activate endothelial cells, platelets, and immune cells, thereby promoting a proinflammatory and prothrombotic phenotype. Furthermore, antiphospholipid antibodies inhibit anticoagulants, impair fibrinolysis, and activate complements. Although CAPS can affect a variety of organs and tissues, the kidneys, lungs, central nervous system, heart, skin, liver, and gastrointestinal tract are most commonly affected. The systemic inflammatory response syndrome, likely to extensive tissue damage, accompanies CAPS. The most frequent renal manifestations are hypertension, proteinuria, hematuria, and acute renal failure. In the majority of patients with CAPS, a precipitating factor such as infection, surgery, or medication can be identified. Antiphospholipid antibodies such as lupus anticoagulant and antibodies against cardiolipin, ß2-glycoprotein I, and prothrombin are serological hallmark of CAPS. Laboratory tests often reveal antinuclear antibodies, thrombocytopenia, and anemia. Despite widespread intravascular coagulation, blood films reveal only a small number of schistocytes. In addition, severe thrombocytopenia is uncommon. Conclusions: Histologically, CAPS is characterized by acute thrombotic microangiopathy. CAPS must be distinguished from other forms of thrombotic microangiopathies such as hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and heparin-induced thrombocytopenia. CAPS is associated with high morbidity and mortality. Therefore, an aggressive multidisciplinary treatment strategy is indicated. Anticoagulation, immunosuppression, plasma exchange, intravenous immunoglobulins, and anti-platelet agents, used in various combinations, have resulted in improved patient outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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41. Antibodies to phosphatidylserine/prothrombin complex in suspected antiphospholipid syndrome in the absence of antibodies to cardiolipin or Beta-2-glycoprotein I.
- Author
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Sanfelippo, MJ, Joshi, A, Schwartz, SL, Meister, JA, and Goldberg, JW
- Subjects
PHOSPHATIDYLSERINES ,IMMUNOGLOBULINS ,DIETARY supplements ,AUTOIMMUNE diseases ,PHOSPHOLIPIDS - Abstract
Antibodies to phosphatidylserine/prothrombin (aPS/PT) complex were measured in 728 serum specimens from patients suspected of having antiphospholipid syndrome (APS), but without diagnostic elevations in the levels of antibodies to cardiolipin or Beta-2 Glycoprotein 1 (β2-GP1). Of the 728 specimens, 41 had elevated levels of aPS/PT. Thrombotic events occurred in 11 of the 22 patients with accessible medical histories. Six of the patients with accessible medical records also had laboratory evidence of the lupus anticoagulant. The identification of aPS/PT in patients without evidence of antibodies to cardiolipin, β2-GP1, or the lupus anticoagulant can contribute to the identification of APS in patients that may go undetected with current testing methods. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
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42. The clinical significance of anticardiolipin antibody levels in patients with acute myocardial infarction: a regional study.
- Author
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Ertaş, Faruk, Can, Öznur, Acet, Halit, and Ozbakkaloglu, Mert
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MYOCARDIAL infarction ,CORONARY disease ,ANTICARDIOLIPIN antibodies ,BLOOD circulation disorders ,IMMUNOGLOBULINS - Abstract
Introduction: Acute myocardial infarction (AMI) will probably remain the most important cause of death over the next decades. Traditional risk factors of atherosclerosis could not exactly explain the development of acute coronary events such as AMI. Antiphospholipid antibody syndrome is a disorder characterized by the development of arterial and venous thrombosis. Aim: In this study, we investigated the relations between acute myocardial infarction and anti-phospholipid antibody syndrome in our population representing Aegean Region people characteristics. Material and methods: One hundred patients with acute myocardial infarction were consecutively included in the study (group I) and one hundred age and sex matched people with similar risk factors were enrolled in the study as a control group (group II). Anticardiolipin antibody (aCL) IgM and IgG levels were measured in the two groups. Levels of aCL IgG ≥ 48 U/ml and/or aCL IgM ≥ 44 U/ml were accepted as positive and significant. Results: In patients with acute myocardial infarction, 5 patients (5%) had positive IgM levels and 8 patients (8%) were found to have positive IgG levels. All cases in the control group had negative aCL IgM and IgG antibody levels. These results were accepted as significant for both aCL antibodies between patients and controls (p < 0.001). Conclusions: We concluded that aCL antibody levels are also higher in a small proportion of patients with acute myocardial infarction than controls in our region, also, and these results suggest that there may be an immune stimulus in the pathogenesis of acute coronary events. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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43. Variability in Exposure of Epitope G40-R43 of Domain I in Commercial Anti-Beta2-Glycoprotein I IgG ELISAs.
- Author
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Pelkmans, Leonie, Kelchtermans, Hilde, de Groot, Philip G., Zuily, Stephane, Regnault, Veronique, Wahl, Denis, Pengo, Vittorio, and de Laat, Bas
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EPITOPES ,GLYCOPROTEINS ,BLOOD coagulation disorders ,ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,GLYCINE - Abstract
Background: A major problem for diagnosing the antiphospholipid syndrome (APS) is the high variability between commercial anti-β
2 glycoprotein I (β2 GPI) assays. Predominantly antibodies reactive against cryptic epitope Glycine40-Arginine43 (G40-R43) in domain I are associated with an increased risk for thrombosis. Upon interaction with anionic surfaces β2 GPI opens up, thereby exposing G40-R43. Objectives: To examine whether suboptimal exposure of epitope G40-R43 explains the variations in results observed between commercial assays. Methods: Two patient-derived monoclonal antibodies were tested on neutral versus anionic plates. Antibody P1-117 reacts with G40-R43 in the open conformation while P2-6 recognizes β2 GPI irrespective of its conformation. These antibodies were tested in commercial anti-β2 GPI assays (A–E). Results: In assay A, both antibodies showed equal reactivity towards β2 GPI, indicating that all the β2 GPI exposes G40-R43. In other assays P1-117 displayed lower reactivity than P2-6, demonstrating reduced G40-R43 availability. To exclude influences of other assay features, reactivity was re-examined on plates of assay A and B using the protocol/reagents from each assay. In all combinations, reactivity of both antibodies on a plate was comparable to results obtained with its own protocol/reagents, suggesting that the coating, rather than other assay components, accounts for the observed differences. In two patient cohorts we demonstrated that a number of domain I-reactive samples are missed in assays characterized by a decreased exposure of epitope G40-R43. Conclusions: Exposure of epitope G40-R43 on β2 GPI is highly variable between commercial anti-β2 GPI assays. As a consequence, patients can be falsely assigned negative in assays characterized by a reduced exposure of G40-R43. [ABSTRACT FROM AUTHOR]- Published
- 2013
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- View/download PDF
44. Annexin A5 anticoagulant activity in children with systemic lupus erythematosus and the association with antibodies to domain I of β2-glycoprotein I.
- Author
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Wahezi, DM, Ilowite, NT, Wu, XX, Pelkmans, L, Laat, B, Schanberg, LE, and Rand, JH
- Subjects
ANNEXINS ,ANTICOAGULANTS ,SYSTEMIC lupus erythematosus ,IMMUNOGLOBULINS ,GLYCOPROTEINS ,DISEASE prevalence ,THROMBOSIS in children ,ATHEROSCLEROSIS prevention ,PATIENTS - Abstract
Children with systemic lupus erythematosus (SLE) have a high prevalence of antiphospholipid (aPL) antibodies and are at increased risk for aPL-related thrombosis. We investigated the association between annexin A5 anticoagulant activity and antibodies to the domain I portion of β2-glycoprotein I (anti-DI antibodies), and propose a potential mechanism for the pathogenesis of aPL-related thrombosis. Using samples from 183 children with SLE collected during the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we examined resistance to the anticoagulant effects of annexin A5, using the annexin A5 resistance (A5R) assay, and evaluated for anti-DI IgG antibodies. Children with SLE had higher frequency of anti-D1 antibodies (p = 0.014) and significantly reduced A5R compared to pediatric controls: mean A5R = 172 ± 30% versus 242 ± 32% (p < 0.0001). Children with SLE and positive anti-DI antibodies had significantly lower mean A5R levels compared to those with negative anti-DI antibodies: mean A5R = 155 ± 24% versus 177 ± 30% (p < 0.0001). In multivariate analysis, anti-DI antibodies (p = 0.013) and lupus anticoagulant (LA) (p = 0.036) were both independently associated with reduced A5R. Children with SLE have significantly reduced annexin A5 anticoagulant activity that is associated with the presence of LA and anti-DI antibodies. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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45. Thrombotic risk in patients with immune thrombocytopenia and its association with antiphospholipid antibodies.
- Author
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Kim, Ki‐Jo, Baek, In‐Woon, Yoon, Chong‐Hyeon, Kim, Wan‐Uk, and Cho, Chul‐Soo
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THROMBOSIS ,ANTIPHOSPHOLIPID syndrome ,IMMUNOGLOBULINS ,CLINICAL medicine ,THROMBOEMBOLISM ,ANTICOAGULANTS ,PROPORTIONAL hazards models - Abstract
Patients with immune thrombocytopenia ( ITP) paradoxically have an increased risk of thrombosis. The presence of antiphospholipid antibodies ( aPL) has been observed in a substantial proportion of ITP patients, but its clinical significance remains to be established. This study retrospectively investigated the prevalence and clinical significance of aPL in ITP patients and assessed the risk factors for thrombosis. One hundred and sixty-five subjects with ITP were included in the study and followed for a mean period of 63·4 months. Sixty-nine (41·6%) patients were positive for aPL at diagnosis, and their clinical characteristics and course of ITP were not different from those of aPL-negative patients. Twenty-one (12·7%) patients developed a thrombotic event during follow-up and the cumulative incidence rate ratio of aPL-positive to aPL-negative patients for thromboembolism was 3·15 [95% confidence interval ( CI) 1·21-8·17] after adjusting for confounding factors. Lupus anticoagulant and hypertension were identified by Cox regression analysis as independent risk factors for thrombosis [hazard ratio ( HR) 4·1, 95% CI 1·4-11·9, P = 0·009 and HR 5·6, 95% CI 1·9-15·8, P = 0·001, respectively]. Our results showed that a substantial proportion of ITP patients were aPL-positive, and that lupus anticoagulant and hypertension were independent risk factors for thrombosis. Detection of aPL can provide useful information for identifying patients at high-risk for developing thrombosis. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
46. Diagnosis of antiphospholipid syndrome in routine clinical practice.
- Author
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Gardiner, C, Hills, J, Machin, SJ, and Cohen, H
- Subjects
ANTIPHOSPHOLIPID syndrome ,PHYSICIAN practice patterns ,IMMUNOGLOBULINS ,LUPUS erythematosus ,OBSTETRICS ,DIAGNOSIS - Abstract
The updated international consensus criteria for definite antiphospholipid syndrome (APS) are useful for scientific clinical studies. However, there remains a need for diagnostic criteria for routine clinical use. We audited the results of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and IgM anticardiolipin (aCL) and anti-ß2glycoprotein-1 antibodies (aß2GPI). Medium/high-titre aCL/aβ2GPI was defined as >99th percentile. Low-titre aCL/aβ2GPI positivity (>95th < 99th percentile) was considered positive for obstetric but not for thrombotic APS. One hundred of the 145 patients fulfilled both clinical and laboratory criteria for definite APS. Twenty-six women with purely obstetric APS had persistent low-titre aCL and/or aβ2GPI. With the inclusion of these patients, 126 of the 145 patients were considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom 12 had aCL only, 37 had aβ2GPI only and 18 positive were for both. The omission of aCL or aβ2GPI testing from investigation of APS would have led to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our data suggest that LA, aCL and aβ2GPI testing are all required for the accurate diagnosis of APS and that low-titre antibodies should be included in the diagnosis of obstetric APS. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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- View/download PDF
47. C6 knock-out mice are protected from thrombophilia mediated by antiphospholipid antibodies.
- Author
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Carrera-Marín, AL, Romay-Penabad, Z, Papalardo, E, Reyes-Maldonado, E, García-Latorre, E, Vargas, G, Shilagard, T, and Pierangeli, S
- Subjects
LABORATORY mice ,ANTIPHOSPHOLIPID syndrome ,THROMBOSIS ,IMMUNOGLOBULINS ,BLOOD proteins - Abstract
Background: Complement activation plays a role in pathogenesis of the antiphospholipid syndrome (APS), but the involvement of the C5b-9 membrane attack complex (MAC) is unknown. Here we studied the effects of human polyclonal antiphospholipid (aPL) antibodies on thrombosis and tissue factor (TF) up-regulation in C6 deficient (C6−/−) mice. Methods: C6−/− mice or the wild-type C3H/HeJ (C6+/+) mice were injected twice with IgG-APS (n = 2) or IgM-APS (n = 1) isolated from APS patients or with the corresponding control immunoglobulins (Igs) of normal human serum, (NHS) (IgG-NHS or IgM-NHS). Then, the sizes of induced thrombi in the femoral vein were determined 72 hours after the first injection. Tissue factor was determined in homogenates of carotid arteries and in peritoneal macrophages. Results: Thrombus sizes were significantly larger in C6+/+ treated with IgG-APS1 or with IgG-APS2 or with IgM-APS when compared with C6+/+ mice treated with IgG-NHS or with IgM-NHS, respectively. The sizes of thrombi were significantly smaller in the C6−/− mice injected with IgG-APS1, IgG-APS2 or IgM-APS (p < 0.001), compared to their C6+/+ counterparts showing an important abrogation of thrombus formation in mice lacking C6. The TF expression and activity in the C6−/− mice treated with IgG-APS or IgM-APS were diminished when compared to C3H/HeJ (C6+/+) mice treated with the same Igs. All mice injected with IgG-APS and IgM-APS had medium-high titers of anticardiolipin (aCL) and anti-β2glycoprotein I (aβ2GPI) antibodies. Conclusions: These data indicate that the C6 component of the complement system mediates aPL-thrombogenic effects, underscoring an important pathogenic mechanism and indicating the possibility of inhibiting complement to ameliorate APS-related manifestations. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
48. Predominant prevalence of arterial thrombosis in Japanese patients with antiphospholipid syndrome.
- Author
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Fujieda, Y, Atsumi, T, Amengual, O, Odani, T, Otomo, K, Kato, M, Oku, K, Kon, Y, Horita, T, Yasuda, S, and Koike, T
- Subjects
THROMBOSIS ,ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases ,IMMUNOGLOBULINS ,BLOOD coagulation - Abstract
Objective: To study the clinical and immunological manifestations of antiphospholipid syndrome (APS) in the Japanese population by a single-centre registration. Methods: In this retrospective cohort study, 141 consecutive patients with APS, fulfilling the Sydney revised Sapporo criteria for definite APS, who visited our autoimmune clinic from 1988 to 2010, were recruited and followed up. All the patients were interviewed and underwent a general physical examination by qualified rheumatologists on the day of blood sampling. Results: The population comprised 119 woman and 22 men with a mean age at diagnosis of 44 years (range 9–79 years). Seventy patients (49.6%) had primary APS, and 71 (50.4%) had systemic lupus erythematosus. The prevalence of thrombosis was 85.8 per cent, arterial thrombosis was found in 93 patients (66.0%) and venous thrombosis was found in 46 patients (32.6%). The most common thrombosis was cerebral infarction [86/141 (61.0%)] followed by deep vein thrombosis [33/141 (23.4%)]. Among 70 pregnant women, 45 (64.3%) had obstetric complications. Lupus anticoagulant was detected in 116 patients (82.3%), anticardiolipin antibodies in 83 (58.9%), anti-β2 glycoprotein I antibodies in 73 (51.8%) and phosphatidylserine-dependent antiprothrombin antibodies in 98 (69.5%). Conclusion: High prevalence of arterial thrombosis was noted in Japanese patients with APS. The profile of heterogeneous and complex clinical manifestations was substantiated in Japanese patients with APS. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
49. Primary antiphospholipid syndrome: morphofunctional penile abnormalities with normal sperm analysis.
- Author
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Rabelo-Júnior, CN, Freire de Carvalho, J, Lopes Gallinaro, A, Bonfá, E, Cocuzza, M, Saito, O, and Silva, CA
- Subjects
ANTIPHOSPHOLIPID syndrome ,FERTILITY ,RHEUMATISM ,IMMUNOGLOBULINS ,SPERMATOZOA - Abstract
Objective: To perform a global gonadal and sexual functions assessment in primary antiphospholipid syndrome (PAPS) patients. Methods: A cross-sectional study was conducted in 12 male PAPS patients and 20 healthy controls. They were assessed by demographic data, clinical features, systematic urological examination, sexual function, testicular ultrasound, seminal parameters according to the World Health Organization (WHO), seminal sperm antibodies, and hormone profile, including follicle stimulating hormone (FSH), luteinizing hormone (LH), morning total testosterone, and thyroid hormones. Results: The median of current age and age of spermarche were similar in PAPS patients and controls (37.5 vs. 32.4 years, p = 0.270, and 13.1 vs. 12.85 years, p = 0.224, respectively), with a higher frequency of erectile dysfunction in the former group (25% vs. 0%, p = 0.044). Further analysis of PAPS patients with and without previous arterial thrombosis demonstrated that the median penis circumference was significantly lower in PAPS with arterial thrombosis than in PAPS without this complication (8.1 [6–10] vs. 10.2 [10–11] cm, p = 0.007). In addition, the median penis circumference was significantly lower in PAPS patients with erectile dysfunction than in patients without this complication (7.5 [6–9.5] vs. 9.5 [7.5–11] cm, p = 0.039). Regarding seminal analysis, the median sperm concentration, sperm motility, and normal sperm forms by WHO guidelines were comparable in PAPS patients and controls (141.5 [33–575] vs. 120.06 [34.5–329] × 106/ml, p = 0.65; 61.29 [25–80] vs. 65.42 [43–82]%, p = 0.4; 21.12 [10–42.5] vs. 23.95 [10–45]%, p = 0.45, respectively), and none of them had oligo/azoospermia. No differences were observed between PAPS patients and controls regarding the frequency of antisperm antibodies, testicular volume by ultrasound, or hormone profile (FSH, LH, morning total testosterone, and thyroid hormone) (p > 0.05). Conclusions: Normal testicular function has been identified in PAPS patients, in spite of morphofunctional penile abnormalities. Previous arterial thrombosis may underlie penile anthropometry alteration. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
50. Republished review: Ocular manifestations of the antiphospholipid syndrome.
- Author
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Utz, Virginia Miraldi and Tang, Johnny
- Subjects
ANTIPHOSPHOLIPID syndrome ,AUTOIMMUNE diseases ,IMMUNOGLOBULINS ,GLYCOPROTEINS ,THROMBOEMBOLISM - Abstract
Antiphospholipid syndrome (APS) is an autoimmune disease characterised by a heterogenous group of antibodies directed against negatively charged phospholipids including antiphospholipid antibodies (aPL), anticardiolipin antibodies (aCL) and β-2 glycoprotein I (ab-2-GP1). The major features of this disorder include arterial and venous thrombosis and recurrent fetal loss. The vasculature of the eye is frequently involved and may be the presenting manifestation. A diagnosis of APS should be considered in a young patients without traditional thromboembolic risk factors presenting with ocular vaso-occlusive disease. Management of these patients involves a team-approach with a haematologist/oncologist or rheumatologist to manage the coagulation status of these patients to prevent further systemic vascular occlusions. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
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