Joint, bone, spine : revue du rhumatisme
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Review Historical Article
Advances in the treatment of systemic lupus erythematosus: From back to the future, to the future and beyond.
There have been many advances in the diagnosis and therapeutic management of systemic lupus erythematosus (SLE) over the past decades. Following more than eleven centuries of therapeutic uncertainty, the discovery of the therapeutic properties of glucocorticoids is without any doubt one of the most significant advance in the field of autoimmune diseases. The many progresses made by rapidly growing chemical industry of the 19th century chemistry have allowed the identification of valuable therapeutic compounds such as anti-malarials, cyclophosphamide, azathioprine, cyclosporine and later mycophenolate mofetil, which have all profoundly changed the face of the disease. ⋯ With the approval of belimumab in 2011 and 74 targeted therapies in clinical development, we may expect great changes in the therapeutic management of SLE. Those molecules target inflammatory cytokines or chemokines and their receptors, B cells or plasma cells, intracellular signalling pathways, B/T cells co-stimulation molecules, interferons, plasmacytoid dendritic cells, as well as various other targets of interest. Current challenges are now slowly shifting from whether some new drugs will be available to how to select the most adequate drug (or drug combination) at the patient-level.
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Histone deacetylation, DNA methylation, and micro-RNAs (miRNAs) are the three main epigenetic mechanisms that regulate gene expression. All the physiological processes involved in bone remodeling are tightly regulated by epigenetic factors. This review discusses the main epigenetic modifications seen in tumoral and non-tumoral bone diseases, with emphasis on miRNAs. ⋯ Advances in the understanding of epigenetic regulation shed new light on the pathophysiology of other non-tumoral bone diseases, including genetic conditions inherited on a Mendelian basis. Finally, in the area of primary and metastatic bone tumors, the last few years have witnessed considerable progress in elucidating the epigenetic regulation of oncogenesis and its local interactions with bone tissue. These new data may allow the development of epigenetic outcome predictors, which are in very high demand, and of innovative therapeutic agents acting via miRNA modulation.