1,721,195 research outputs found
Pathogenesis of the antiphospholipid syndrome : an additional example of the mosaic of autoimmunity
No full textThe antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self-PL-binding proteins ending in the production of specific autoantibodies. Antiphospholipid antibodies (aPL; and in particular anti-β2 glycoprotein I antibodies) are formal diagnostic markers and pathogenic antibodies. Although APS may be considered as an autoantibody-mediated disease, there is now evidence that aPL are necessary but not sufficient to trigger some of the clinical manifestations of the syndrome. For example, additional factors, such as mediators of the innate immunity are now recognized to play a key role as second hits able to induce the thrombotic events in the presence of the autoantibodies. The APS scenario is also supplemented by the influence of genetically determined factors. Finally, environmental agents - in particular infectious ones - were reported to act as triggers for the production of autoantibodies cross-reacting with PL-binding proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic effect. Altogether these findings do support the concept of a mosaic of factors that participate to the pathogenesis of the syndrome at different levels
The geoepidemiology of the antiphospholipid antibody syndrome
No full textAntiphospholipid antibodies (aPL) can be detected by functional (lupus anticoagulant) and/or by solid phase assays (anti-cardiolipin and anti-beta2 glycoprotein I). Although detectable in 1-5% of asymptomatic apparently healthy subjects, persistent aPL are significantly associated with recurrent arterial/venous thrombosis and with pregnancy morbidity. Such an association is the formal classification tool for the antiphospholipid syndrome (APS). The prevalence of the syndrome with no associated systemic connective tissue diseases (primary APS) in the general population is still a matter of debate since there are no sound epidemiological studies in the literature so far. aPL display higher prevalence in systemic lupus erythematosus and rheumatoid arthritis than in other systemic autoimmune diseases. However not all the aPL positive lupus patients display the clinical manifestations. Comparable findings may be found in the paediatric population, although anti-beta2 glycoprotein I antibodies are detected in healthy children more frequently than in adults. High prevalence of aPL has been also reported in clinical manifestations that are not formal APS classification criteria: heart valve disease, livedo reticular, nephropathy, neurological manifestations, and thrombocytopenia. Antiphospholipid antibodies can be associated with infectious processes, active vaccination, drug administration and malignancies. Their prevalence and titres are lower and the relationship with the APS clinical manifestations are less strong than in the previously mentioned conditions. Ethnicity was also reported to influence the prevalence of aPL
Predictive, protective, orphan autoantibodies : the example of anti-phospholipid antibodies
No full textAnti-phospholipid antibodies (aPL) are one of the most recent examples of autoantibodies that can appear even long time before any clinical manifestation can be associated with them. There is a general agreement that they may represent a strong risk factor for recurrent thrombosis and/or fetal losses. Anti-phospholipid antibodies represent a necessary but not sufficient factor (first hit) for thrombosis, and require additional triggering factors (second hit) to disclose the thrombogenic activity. Several factors may affect the predictive value of aPL, including titre, immunoglobulin isotype, fine antigenic specificity and affinity binding activity. Their careful evaluation is suggested in order to characterize the true predictive value of aPL
Pathogenic mechanisms mediating antiphospholipid syndrome
No full textAntiphospholipid antibodies are the marker for antiphospholipid syndrome. There is evidence that these autoantibodies lead to both thrombotic diathesis and obstetrical manifestations. Besides the known interaction with soluble coagulation factors, in vitro and in vivo experimental models and studies in humans recently have shown the ability of antiphospholipid antibodies to modulate functions of cells involved in coagulation homeostasis. These findings support a new hypothesis to explain the paradox of the prolongation of coagulation assays in vitro and the association with thrombophilic diathesis in vivo. Obstetrical manifestations have been linked to a direct antibody effect on the trophoblast leading to defective placentation that is not necessarily associated with thrombotic phenomena. Phospholipid binding proteins such as beta 2 -glycoprotein I appear to behave as a bridge between circulating antiphospholipid antibodies and cellular targets
[Quality and efficiency of the Health Service in the Italian Region of Lombardy]
No full textThe Regional Law No. 31 of 1997 has revised the Lombardy Health Service as a whole, separating "providers", credited Public and Private Health Institutions, from "purchasers", Local Health Agencies. To this purpose, the improvement of the quality of assistance has been enhanced through an accreditation process aimed at implementing second level regional requirements considered as being necessary for carrying out effective treatment and meeting patient needs. Training, implementation and evaluation of quality service within Health Institutions have been carried out with the assistance of the Regional Observatory on the Quality of Health Service, which helped to identify initial intervention areas, define process indicators, activities and outcomes and verify patient satisfaction, all this to improve performance, reduce risks and control costs. To fully develop the Institutions in the accreditation process, the complex and difficult aspect of health care quality has been more extensively and deeply dealt with by adopting an "Excellence accreditation" model in cooperation with the Joint Commission International Accreditation and by experimenting with Professional accreditation supported by Scientific Societies to further contribute to the development of technical skills and knowledge. The Quality Project carried out so far is based on the integration of various projects, which will be the object of practical interventions by the General Health Direction. All the information and results gathered from this project will be very helpful in finding solutions that will enable all Health Institutions in Lombardy to reach an adequate level of quality
Autoimmune or auto-inflammatory syndrome induced by adjuvants (ASIA) : old truths and a new syndrome?
No full textThere has been considerable interest in the role of environmental factors and the induction of autoimmunity and the ways by which they facilitate loss of tolerance. Clearly both genetic and environmental factors are incriminated, as evidenced by the lack of concordance in identical twins and the relatively recent identification of the shared epitope in rheumatoid arthritis. In this issue a new syndrome called 'Asia'-autoimmune/auto-inflammatory syndrome induced by adjuvants has been proposed. It is an intriguing issue and one that is likely to be provocative and lead to further biologic and molecular investigation
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