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An inverse relationship between BMI and risk of death has been noted in patients with rheumatoid arthritis. Does being overweight or obese really have a favourable effect on mortality in these individuals, or could other factors explain the association?

The contributions of key cytokines in rheumatoid arthritis (RA) pathogenesis, including TNF, IL-1, JAK-dependent cytokines, GM-CSF and chemokines, can be considered not only individually, but also in the context of an overall 'RA tissue response'. In this Opinion article, the authors provide an overview of the roles of cytokines in the innate, adaptive and stromal immune responses, and discuss how systematic analysis of cytokine pathways could yield new insights into disease pathogenesis and facilitate stratification for therapy.

Discerning which mediators drive pathogenesis in chronic inflammatory diseases can be complex: immune cells can release various pathogenic cytokines, and numerous cytokines may either cause one specific disease or many. Human validation and mechanistic studies will be necessary to identify the key immune cells and cytokines for a given inflammatory disorder and to pinpoint which cytokine might be the appropriate target for tackling each disease. In 'Bedside to Bench', Georg Schett et al. discuss how human trials targeting different cytokines suggest the existence of a hierarchical framework of cytokines that defines groups of chronic inflamatory diseases rather differently from the homogenous molecular disease pattern previously assumed. In 'Bench to Bedside', Vijay Kuchroo and Dominique Baeten peruse the role of interleukin-17A as drug target in several autoimmune diseases to highlight how success in the clinic will need understanding of pathogenic pathways and the immunological and tissue context of each inflammatory disease.

Despite having increased cardiovascular risk, patients with rheumatoid arthritis (RA) often have low serum cholesterol levels. In this Review, the authors discuss this putative 'lipid paradox', highlighting the relationships of inflammation and anti-inflammatory therapy with lipid profiles in RA.

Pathways associated with inflammation are thought to account for increased vascular risk in patients with chronic inflammatory diseases. This Review summarizes key epidemiologic, physiologic and model data that implicate involvement of tumor necrosis factor, a pivotal cytokine in the inflammatory cascade, in atherosclerosis.

Advances in our understanding of immune cell receptors and the development of biologic agents targeting them have revolutionized the treatment of rheumatoid arthritis (RA). Now, inhibitors of kinases integral to the signalling pathways downstream of these receptors have been added to the therapeutic armamentarium. This Review discusses the signalling pathways and small-molecule inhibitors of their component kinases that have already shown, or are predicted to show, promise in the treatment of RA.

The field of rheumatology has seen remarkable progress in the past 70 years. This Perspectives article provides a concise overview of developments in the diagnosis and management of musculoskeletal rheumatic diseases, and what the future of rheumatology might hold.

Tendon disorders are common and confer a large socioeconomic burden. This Review discusses the role of inflammatory mechanisms in tendon homeostasis and resolution of tendon damage, which are crucial to consider in developing novel therapeutics for tendinopathies.

Advances in synovial tissue research have improved our understanding of inflammatory arthritides, particularly rheumatoid arthritis, and have identified potential biomarkers that could be used for diagnosis, disease stratification, and predicting disease course and treatment response.

Several molecular pathways and cellular effector functions have been described for the pathology of rheumatoid arthritis, but fundamental questions remain about the basic organization of disease-driving immune responses. In this Review, Benson and colleagues describe how intact tissue imagingin vivohas facilitated studies of the dynamic nature of cellular immune responses, and how these findings can be translated to new therapeutics.

There are multiple immune-based therapeutics available for some of the most prevalent autoimmune diseases, but for others, there are few or no approved immune therapies. This dichotomy poses discrete challenges. First, for diseases in which multiple therapy choices exist, a rational decision tree is required to select the best therapy. Second, we must devise new strategies for the autoimmune diseases that have the highest unmet clinical need. This commentary outlines new strategies for designing more efficient and selective approaches for immune therapy of autoimmune diseases.