Catálogo de publicaciones - libros

The use of TNFα inhibitors has provided clear evidence for the direct role of cytokines in complex inflammatory diseases. The simplest approach, already in practice, is the specific inhibition of their action. The stimulation of endogenous regulatory mechanisms can represent a more physiological way to restore an adequate balance. The lack of response and the occurrence of adverse reactions observed in some patients exposed to cytokines and their inhibitors imply taking into account the level of production and regulation of the target cytokines. Part of such heterogeneity is genetically determined. Considering these issues will allow a better risk-benefit assessment of the treatment for each patient.

The role of stem cell transplantation in the treatment of severe, therapyrefractory AD remains experimental, with data on around 700 patients being sufficiently encouraging to proceed to randomized prospective trials in the major diseases: SSc, RA, MS, and soon JIA and SLE. An impressive international collaboration has and is reducing duplication of efforts with shared databases, protocols, patient selection, and end points. The concept of resetting a dysbalance in the complex immune network, rather than total eradication of clonal autoimmunity, is emerging. Further clinical trials are required to establish the place, if any, HSCT has in such treatment, and a basic science program continues to explain the pathophysiological mechanisms of these immune-modulating strategies.

Studies in recent years have shown that the immune system plays a greater role in the pathogenesis of atherosclerosis than previously recognized. These findings open new possibilities of treatment or prevention of this disease, and approaches using antibodies are especially promising. Future studies should aim at further characterizing the fine specificities of beneficial antibodies and at optimizing the means of their delivery (active immunization versus passive administration).

Antigen-specific therapy is a promising avenue for treating autoimmune diseases. The protection after vaccination with autoantigens in a tolerogenic manner is mediated by the induction of regulatory T cell populations. The exact nature of these Tregs is variable, depending on the type of therapy, but in general they mediate their protective effect by bystander suppression. This process involves the production of anti-inflammatory cytokines such as IL-4, IL-10, and TGF-β, as well as cell-cell contact with the same APC that encounters the autoaggressive T cells. The effectiveness of antigen-specific therapy is influenced by many factors such as antigen selection, and the route and timing of immunization. In addition, the exact dynamics of the T cell repertoire in the host, as well as the particular disease in question, needs to be considered when applying such a therapy. So far, in animal models, success has been achieved in the prevention of autoimmune diseases like T1D and EAE after vaccination with autoantigens via a mucosal or nasal route, and also after immunization with naked plasmid DNA expressing autoantigens. In contrast, it has, as of yet, been more difficult to see an immediate benefit in human clinical trials. However, by applying strategies such as systemic therapies aimed at reducing the autoaggressive T cells with antigen-specific therapy, the results may be improved. This type of strategy, along with the development of techniques to track autoaggressive and regulatory T cells in the blood, will likely make antigen-specific therapy an effective means of treating autoimmune diseases.