1,721,105 research outputs found
Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations
No full textIn recent years, antiphospholipid antibodies (aPL) and their associated clinical features have been recognized increasingly in various pediatric autoimmune and non-autoimmune diseases. Pathogenic mechanisms involved in pediatric antiphospholipid syndrome (APS) appear to be the same as in adults. However, since pediatric patients do not have prothrombotic risk factors present in adults, there clearly are differences in the spectrum of clinical findings. The frequency of aPL-related thrombotic events is generally low in pediatric populations. On the other hand, various commonly acquired infections are likely to be responsible for higher percentage of non-pathogenic and transient aPL in childhood. Such points have to be considered in clinical judgment of elevated aPL in children. In this review we summarize the recent data on the prevalence and clinical significance of aPL in neonates, children and adolescents
Do we need an international consensus statement on classification criteria for the antiphospholipid syndrome in the paediatric population?
No full textAnti-inflammatory and immunomodulating properties of statins. An additional tool for the therapeutic approach of systemic autoimmune diseases?
No full textCardiovascular diseases secondary to accelerated atherosclerosis are now accepted as a cause of mortality and morbidity in patients suffering from systemic lupus erythematosus and rheumatoid arthritis. More recently, atherosclerosis is emerging as one of the most serious complications in the anti-phospholipid syndrome, although large epidemiological studies, such as those performed in lupus and rheumatoid arthritis patients, have not been performed up to now. Classical risk factors (dislipidemia, hypertension, diabetes, smoking, etc.) and steroid therapy cannot completely explain the high prevalence of cardiovascular complications in systemic autoimmune diseases. Since the modern view defines atherosclerosis as a chronic inflammatory disorder, it has been suggested that systemic inflammation and soluble immune mediators (circulating autoantibodies, immune-complexes, complement activation products) might play a role in accelerating vessel pathology. The main target appears to be the endothelium because of its ability to switch to a pro-adhesive, pro-inflammatory and pro-coagulant surface in response to these mediators. Recent advances in the knowledge of the pharmacology of statins have indicated that these drugs rather than to be simple cholesterol lowering molecules display a pleiotropic effects on several mechanisms involved in the atherosclerotic plaque formation. Their anti-inflammatory activity and particularly their ability to downregulate endothelial cell activation induced by different stimuli strongly suggest their possible use in conditions in which the systemic inflammation and the endothelial activation/damage are thought to represent key pathogenic mechanisms
Human lymphocyte surface markers after allogeneic activation: increase of Fc receptors-bearing cells
No full textThe behaviour of human lymphocyte surface markers was investigated after in vitro alloactivation. Evidence was obtained that the expression of surface receptors is modified during mixed lymphocyte culture. In vitro allogeneic stimuli are able to induce a very significant increase of Fc receptors bearing cells: the biological significance of these data is discussed
Potential effect of anti-inflammatory treatment on reducing the cardiovascular risk in rheumatoid arthritis
No full textRheumatoid arthritis (RA) is a chronic inflammatory polyarthritis with increased mortality largely attributable to cardiovascular disease. There is extensive evidence that patients with RA experience accelerated atherosclerosis, which is considered as the main responsible of this increased cardiovascular burden. Nowadays atherosclerosis is regarded as an inflammatory condition: hence, the cumulative inflammation of RA, with the abundant synthesis of proinflammatory cytokines, contributes directly to the early formation of the atheromatic plaque. It is therefore reasonable to postulate that, by alleviating inflammation, drugs commonly used in RA treatment may ameliorate the cardiovascular profile of these patients. Here we provide an extensive review of the literature, focusing on the effects of the available anti-rheumatic agents on cardiovascular mortality, and morbidity among RA sufferers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Endothelial cell activation by antiphospholipid antibodies
No full textAntiphospholipid antibodies are mainly directed against beta 2 glycoprotein I, a phospholipid-binding protein expressed on endothelial cell membranes of different anatomical localizations and recognized by the specific autoantibodies. Antibody binding induces an endothelial activation both in in vitro and in vivo experimental models that might contribute to the prothrombotic state. Endothelial beta 2 glycoprotein I adhesion is mediated by the electrostatic interaction between its cationic phospholipid binding site and anionic structures on the cell membrane; however, binding to annexin II--the endothelial cell receptor for tissue plasminogen activator--plays also a role. Anti-beta-2 glycoprotein I antibodies up-regulate mRNA expression of pro-inflammatory mediators through NF-kappaB translocation and the signaling cascade triggered by Toll-like receptors. Because of the molecular mimicry between beta 2 glycoprotein I and viral/bacterial structures-the natural ligands for Toll-like receptors (TLR)-antibodies might cross-link the molecule associated to the receptors eventually triggering their signaling
TOLL-LIKE RECEPTOR 4 AS A CELL MEMBRANE RECEPTOR FOR BETA2 GLYCOPROTEIN I
No full textBackground: Antiphospholipid Syndrome (APS) is characterized by recurrent fetal losses and arterial/venous thrombosis in the presence of aPL1. aPL are directed against anionic phospholipid binding proteins: mainly prothrombin and beta2 glycoprotein I (β2GPI). The complex formation between circulating aPL and β2GPI expressedon the cell membranes induces signalling and triggers cell activation2,3. The exact nature of the EC receptors for β2GPI is still matter of research: heparan sulphate, Annexin A2 and apoER2 have been suggested to be candidate molecules4. Furthermore there is also evidence that aPL trigger TLR-4 dependent cell signalling.
Objectives: To address the role of TLR4 as cell membrane receptor for β2GPI and its involvement in anti-β2GPI Abs-mediated EC activation pathway.
Methods: We performed: i) in vitro experiments with or without blocking antibodies directed to Annexin A2 and TLR-4; ii) small interfering RNA experiments for silencing TLR-4 and Annexin A2 expression in suitably transfected HUVEC; iii) confocal microscopy studies to visualize in real time the binding and internalization of β2GPI and aPL in living MOCK and TLR-4-transfected (TLR-4+) CHO cells.
Results: TLR-4 silencing by siRNA significantly inhibited both binding and activation of aPL-exposed HUVEC, while Annexin A2 silencing only affected binding. Fluoresceinated β2GPI bound to TLR-4+ CHO more strongly and persistently as compared to MOCK CHO. Membrane binding was followed within minutes by internalization in granular structures in TLR-4+ cells only. Experiments are being set up to evaluate the effects of anti-β2GPI Abson this event.
Conclusions: Our results suggest that more than one receptor may be involved in aPL-mediated EC activation. However, TLR-4 appears particularly relevant as it seems necessary for β2GPI internalization in cells and Annexin A2, lacking a cytoplasmic tail, is unable to transduce signals. Understanding in detail the mechanisms of β2GPI and β2GPI-aPL complex interaction with plasma membrane will lead to identify new strategies for treatment and prevention of pro-thrombotic and pro-inflammatory state in APS.
References:
Miyakis, S., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 2006: 4, 295-306.
Giannakopoulos, B., et al. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood 2007: 109, 422-430.
de Laat, B., et al. Mechanisms of disease: antiphospholipid antibodies-from clinical association to pathologic mechanism. Nat. Clin. Pract. Rheumatol. 2008: 4, 192-199.
Pierangeli SS, et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin Thromb Hemost. 2008: 34, 236-50
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