1,721,270 research outputs found
Rheumatoid Factors
No full textRheumatoid factors (RFs) are autoantibodies reacting against the Fc region of immunoglobulin (Ig)G. RFs are the first autoantibodies described in rheumatoid arthritis (RA), although they are also present in several other autoimmune diseases, in infectious conditions, as well as in healthy subjects. They are currently detectable by standardized quantitative assays (enzyme-linked immunosorbant assay, nephelometry), which are more reliable than the original semiquantitative agglutination techniques. Whether RFs display a pathogenic role in RA is still unclear; however, in favor of such a hypothesis are: i) their ability to form immune complexes both locally – in the synovial space – and systemically; ii) their association with aggressive disease characterized by erosive arthritis and extra-articular manifestations; and iii) the decrease in RF titers after successful therapy with disease-modifying antirheumatic drugs and biologic agents. Although a strong effort has been made in the last decade to find new powerful biomarkers particularly for the early stage of RA, RFs are still one of the most reliable diagnostic/prognostic biomarkers for RA
Anti-beta-2 glycoprotein I epitope specificity : from experimental models to diagnostic tools
No full textBeta-2 glycoprotein I (β2GPI) is the main antigenic target for anti-phospholipid antibodies (aPL), the serological markers of anti-phospholipid syndrome (APS). Conformational changes of the molecule seem to be essential for exposing the cryptic epitope for aPL binding and to trigger pathogenic pathways. There is increasing evidence that a conformational epitope located in the Domain I (DI) of the molecule is the main epitope targeted by human autoantibodies. The pathogenic role of the DI epitope has been recently supported by in vivo models and by immuno-histopathological findings in APS patients. Antibodies targeting β2GPI-DI are more frequently detected in patients with full-blown APS compared to asymptomatic aPL carriers or patients with infectious diseases who have antibodies directed against the whole molecule. Anti-DI antibodies are positively correlated with medium to high titres of aPL, with the presence of lupus anticoagulant and thrombotic and pregnancy manifestations, enabling identification of patients at higher risk of clinical events. However, some APS patients develop antibodies reacting against β2GPI epitopes other than DI, suggesting that other anti-β2GPI antibody subsets may be clinically relevant. Although preliminary results suggest that anti-DI antibodies can be detected by different assays in a comparable manner, further prospective studies are needed to support their use in the clinical setting and their predictive value
Prevention & treatment of obstetrical complications in APS : Is hydroxychloroquine the Holy Grail we are looking for?
No full textPregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory
Aspirin in asymptomatic patients with confirmed positivity of antiphospholipid antibodies? Yes (in some cases)
No full textNew oral anticoagulants in thrombotic antiphospholipid syndrome
No full textA main goal in clinical management of patients with antiphospholipid syndrome (APS) is to prevent thrombotic recurrences and/or miscarriages. For many decades, the only available oral anticoagulant drugs have been vitamin K antagonists (VKA), which are still the cornerstone of long-term treatment of thromboembolism. However, the limits of VKA treatment are well known: narrow therapeutic window and high patient-to-patient variability of response. Moreover, in some patients with APS a higher international normalized ratio (INR) therapeutic target was suggested, and INR inaccuracy due to antiphospholipid antibodies was reported. Therefore, VKA management in APS patients is frequently cumbersome, requires close INR monitoring and may affect patient's quality of life. A new class of oral anticoagulant agents has been developed, the Direct Oral Anticoagulants (DOA), which directly inhibit a single enzyme of the coagulation cascade. Compared with VKA, they have more stable pharmacokinetic and pharmacodynamic profiles, little interaction with food or drugs with a predictable anticoagulation effect, they can thus be prescribed in a fixed dose, without requiring frequent laboratory monitoring. The efficacy and safety of DOA has been shown in large phase III clinical trials. Unfortunately, translating these good results to APS patients is not straightforward: currently, at least three randomized controlled clinical trials are ongoing
Recognition and management of antiphospholipid syndrome
No full textPurpose of review This article summarizes the recent developments in the recognition and management of antiphospholipid syndrome (APS). Recent findings Five Task Forces, created as part of the 14th International Congress on antiphospholipid antibodies (aPL), published their systematic reviews. 'For the recognition of APS': the assessment of aPL profile is crucial for risk stratification; lupus anticoagulant positivity, especially in the context of 'triple aPL positivity' displays the highest risk; a panel of criteria and noncriteria aPL tests may help better risk-stratify the aPL-positive in the future. 'For the management of APS': direct oral anticoagulants are not currently recommended; statins ameliorate the proinflammator/thrombotic markers, whereas hydroxychloroquine reduces the risk of thrombosis in experimental models and lupus patients, which justify their use as an adjunctive treatment in refractory cases; B-cell inhibition may have a role in difficult-to-treat patients with hematologic and microthrombotic/angiopathic manifestations; and complement and mammalian targets of rapamycin complex pathway inhibition are promising targets in APS. Summary Warfarin, heparin, and/or antiplatelet drugs are the standard of care for aPL-positive patients. Recent studies suggest novel approaches that target new coagulation and immunomodulatory pathways; mechanistic and/or controlled clinical studies are needed to determine the effectiveness of these novel approaches
Power Doppler sonography and clinical monitoring for hyaluronic Acid treatment of rhizarthrosis : a pilot study
No full textTrapeziometacarpal (TMC) joint osteoarthritis (OA) is a common disabling condition in which the impact of visco-supplementation has to be ascertained. We aim to evaluate the efficacy of high molecular weight hyaluronic acid (HA) ultrasound (US)-guided intra-articular injection of TMC joints in OA. 32 TMC joints of 16 patients with symptomatic thumb base OA were treated with three injections of high molecular weight HA at 1-week intervals. Before injection, at week 0, 1, 2, and 24 all patients underwent clinical and US examination. A significant clinical improvement was obtained by the decrease in visual analog scale for pain after 2 weeks of treatment (p = 0.0003) and this result is maintained at week 24 (p = 0.009). The Dreiser's index also decreased after week 2 and remain stable after 6 months. Power Doppler signal significantly decreased after 2 weeks of treatment (p = 0.02), even if this result was not maintained at week 24. No significant decrease in the synovial hypertrophy score was observed during the study. Our preliminary study suggests that US-guided TMC injections by high molecular weight HA may be effective in decreasing local inflammation and pain
Antiphospholipid antibody mechanisms of thrombosis
No full textAnti-phospholipid antibodies (aPL) are diagnostic and pathogenic antibodies. There is evidence from both in vitro and in vivo models that they can mediate thrombosis through several mechanisms. aPL may interact with beatta-2 glycoprotein I or with prothrombin and may interfere with fluid- phase coagulation steps: inhibition of protein C-S activity and fibrinolysis. More importantly beta-2 glycoprotein I –dependent aPL may recognize their own target on several cell types involved in the coagulation: endothelial cells, peripheral blood monocytes, and platelets. Once bound aPL may induce a pro-inflammatory and pro-coagulant endothelial phenotype, may induce tissue factor expression on monocytes, and can increase aggregation of platelets stimulated by another agonist. All these mechanisms may play a role in supporting the thrombophilic state of the anti-phospholipid syndrome. aPL are necessary for clotting but are not sufficient and require an additional stimulus (two- hit theory) and complement activation so explaining why thrombosis can occur only sometimes in spite of the persistent presence of the antibodies
Novel Mechanisms of Action of the Biologicals in Rheumatic Diseases
No full textBiological drugs targeting pro-inflammatory or co-stimulatory molecules or depleting lymphocyte subsets made a revolution in rheumatoid arthritis (RA) treatment. Their comparable efficacy in clinical trials raised the point of the heterogeneity of RA pathogenesis, suggesting that we are dealing with a syndrome rather than with a single disease. Several tumor necrosis factor-alpha (TNF-α) blockers are available, and a burning question is whether they are biosimilar or not. The evidence of diverse biological effects in vitro is in line with the fact that a lack of efficacy to one TNF-α agent does not imply a non-response to another one. As proteins, biologicals are potentially immunogenic. It has been recently raised that anti-drug antibodies (ADA) may affect their bioavailability and eventually the clinical efficacy through local formation of immune complexes and directly by preventing the interaction between the drug and TNF-α. Regular monitoring of drug and ADA levels appears the best way to tailor anti-TNF-α therapies. Owing to the pleiotropic characteristics of the target, anti-TNF-α blockers may affect several mechanisms beyond rheumatoid synovitis. As TNF-α plays a pivotal role in the induction of early atherosclerosis, treatment with TNF-inhibitors may modulate cholesterol handling, in particular, cholesterol efflux from macrophages. Side effects are a major issue because of the systemic TNF-α blocking action. The efficacy of an anti-C5 monoclonal antibody fused to a peptide targeting inflamed synovia in experimental arthritis opened the way for new strategies: Homing to the synovium of molecules neutralizing TNF would allow to maximize the therapeutic action avoiding the side effects
- …
