Lancet
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The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. ⋯ UK Medical Research Council and British Heart Foundation.
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Review
Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment.
Increased understanding of the molecular mechanisms underlying the pathogenenesis of autoimmune rheumatic diseases has led to targeted biological treatments that modulate various aspects of the immune response. These new treatments, together with more judicious use of other immunosuppressive drugs, have resulted in marked improvements in morbidity and mortality. Although belimumab, an agent that inhibits B-cell survival, is the first drug to be approved by the US Food and Drug Administration for the treatment of systemic lupus erythematosus in 50 years, many other immunological targets are under investigation. We discuss the recent advances in the biological treatment of autoimmune rheumatic diseases, with a particular focus on systemic lupus erythematosus.
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Systemic lupus erythematosus, Sjögren's syndrome, and dermatomyositis are systemic autoimmune diseases that develop after environmental triggering of genetically susceptible individuals. The precise cellular and molecular mechanisms leading to autoimmune disease, and what factors determine which organs are involved, remain poorly understood. Recent insights into genetic susceptibility now make obvious that environmental triggers often act via cellular pathways containing disease-associated polymorphisms. ⋯ Type 1 interferon produced by innate immune cells has a central role in systemic autoimmunity and activates B cells and T cells. In turn, B-cell-derived autoantibodies stimulate dendritic cells to produce type 1 interferon; thus, a positive feedforward loop is formed that includes both the innate and adaptive systems. New treatments could simultaneously and specifically target several such vital pathways in autoimmunity.