Review Articles in 2014

The molecular mechanisms that underlie the development of osteoarthritis (OA) remain poorly understood. Here, Fang and Beier summarize the various mouse models of OA (including surgical, mechanical loading, genetic, spontaneous, high-fat diet and/or obesity, and chemically-induced models) that can be used in OA research to further understanding of disease development. The currently available tools for assessment of these models are also discussed.

In this article the authors review the 'BAFF/APRIL system', a complex of the cytokines BAFF and APRIL, their receptors and signalling pathways. The efficacy of belimumab, an anti-BAFF biologic agent used in clinical trials for SLE, is used to develop an argument that the BAFF/APRIL system is an important regulator of autoimmunity. Future therapies for SLE could fine-tune these cytokine signalling pathways to regulate autoreactive B cell survival and autoimmunity.

Despite the availability of effective treatments, the clinical management of gout is frequently suboptimal, leading to continued acute attacks and the risk of irreversible joint damage in many patients. In this article, the authors review the available treatments and barriers to successful management, and discuss how gout could be 'cured' by improving the current standard of care, with individualized management plans incorporating patient education, application of recommended best practice and shared decision-making.

High-resolution peripheral quantitative CT (HR pQCT) has emerged as a unique way to evaluate bone and joints, by producing high-resolution, 3D images of cortical and trabecular bonein vivo. In this Review, the authors describe how HR pQCT is used in the evaluation of bone and joint diseases, together with an evaluation of its technical features, advantages, limitations, and potential in basic research, clinical trials and clinical practice.

Pain is subjective and depends on the context in which it is experienced. In this Review the authors examine the effect of expectation (negative and positive), and other contextual factors, on the differential activation of neurochemical pathways and the sensation of pain and effectiveness of analgesia. The reviewers use data from placebo and nocebo response experiments to argue that the overall context, including the relationship between patient and doctor, can control the effectiveness of pharmaceutical intervention.

Although effective treatments for rheumatoid arthritis are now available, many patients are found to be unresponsive to, or cannot tolerate, particular therapeutic options; therefore, selecting the most appropriate treatment on an individualized basis is important. Genetic and epigenetic factors probably represent key determinants of a patient's response to therapy, and herein the potential of such factors as predictive biomarkers of therapeutic responsiveness is discussed.

Extracellular vesicles are now thought to mediate inflammation and immunity by carrying PAMPs, DAMPs, autoantigens, microRNAs, cytokines and various metabolites and cellular components. In this Review, the authors put these findings in the context of rheumatic diseases and hint at the future of therapies that might use extracellular vesicles to modulate immune responses.

Eicosanoids are major regulators of inflammation and are thought to be involved in the pathogenesis of rheumatic diseases. Here, the authors provide an overview of eicosanoid pathways in a variety of rheumatic diseases (including rheumatoid arthritis, osteoarthritis and gout, among others) and describe how targeting this pathway might lead to novel anti-inflammatory treatment strategies.

In systemic lupus erythematosus (SLE), central nervous system involvement can present as various neurological and psychiatric features, as a primary manifestation of SLE or arising from other causes. In this Review, the author discusses advances in knowledge of the immunopathogenesis, diagnosis and management of neuropsychiatric events in patients with SLE.

That many autoimmune rheumatic diseases have an extended preclinical period, during which autoimmunity develops and evolves, is becoming apparent. In this Review, the authors discuss the current knowledge of the preclinical pathogenesis of rheumatoid arthritis and systemic lupus erythematosus, and use these diseases as models to highlight how such understanding could, in the future, improve therapeutic intervention and even lead to preventative approaches in autoimmune rheumatic diseases.

Pain is a debilitating symptom of juvenile idiopathic arthritis (JIA) that can persist despite effective disease control. Insights into the underlying mechanisms of pain in JIA could highlight new treatment approaches and improve management. Here, the neurobiological basis of pain in JIA is described, using findings from animal models to inform the situation in humans.

Hand osteoarthritis (OA) is a common disease and the prevalence is expected to increase further with ageing of the general population. In this comprehensive Review, Margreet Kloppenburg describes the nonpharmacological and pharmacological management strategies currently available to alleviate the symptoms of hand OA.

Although patients with rheumatoid arthritis now have a better prognosis than those individuals who were diagnosed in previous decades, treatment decisions are still not individualized. In this Review, Annette van der Helm-van Mil describes state of the art approaches to predict disease risk, disease progression, and patient response to therapy.

In this Review the authors provide an account of prostaglandin and leukotriene involvement in muscle health and function. Various components of the arachidonic acid cascade are discussed in relation to their effect on the pathogenesis of inflammatory muscular diseases. Selective modulation of individual components of these pathways are considered as potential therapeutic options for the treatment of polymyositis and dermatomyositis.

In this Review, the authors provide an overview of the role of T cells in rheumatoid arthritis (RA) with insights from mouse and human studies. They examine the similarities and differences between RA and mouse arthritis models with respect to T-cell subsets and functions, and also discuss the implications for potential therapies for RA.