Review Articles in 2016

Macrophages, which have roles in the pathogenesis and resolution of rheumatoid arthritis, consist of a heterogeneous population of cells with different origins and functions. This Review describes these properties, and considers the potential for therapeutic targeting of specific macrophage subtypes.

Autophagy underlies the cellular pathology of several rheumatic diseases. Targeting the signalling pathways involved has shown promise in recent clinical trials. Rockel and Kapoor discuss the key regulators involved in autophagy and therapeutic strategies currently in use and under development.

A growing body of evidence implicates the human gut microbiota in health and in disease, including spondyloarthritis, psoriatic arthritis and rheumatoid arthritis. This article explores the ways in which the microbiota influences innate and adaptive immune responses in the host.

Emerging evidence suggests the nervous system, including the circadian timing system, influences susceptibility to osteoarthritis (OA) via direct and indirect effects. This Review describes the interactions between the brain and the joints in the context of OA, ageing, obesity and inflammation, and outlines therapeutic and research opportunities in this field.

This Review provides an overview of new discoveries that are changing our understanding of the complex role of the human gut microbiota and its metabolites in health and disease, including their effects on rheumatic diseases. Factors that modulate the microbiota, such as diet and probiotics, and advances in pharmacomicrobiomics are also discussed.

Besides their well-known role in cell death mechanisms, CD8⁺ T cells are now emerging as critical mediators of autoimmune diseases. CD8⁺T-cell homeostatic changes under inflammatory conditions, such as phenotypic variation and impaired regulation, provide insights into the pathogenesis of autoimmune arthritis and potential therapeutic targets.

In this article, the authors provide a comprehensive and timely review of the mechanisms and consequences of hypoxia in the biology of inflammatory arthritis, with a focus on mitochondrial function, hypoxia signalling pathways in rheumatoid arthritis, and therapeutic implications.

Although changes associated with ageing promote the development of osteoarthritis (OA), ageing and OA are independent processes. In this Review, the authors discuss the mechanisms by which age-related factors contribute to OA through effects on articular cartilage and propose that future improvements in our understanding of these mechanisms will inform new therapies to slow or stop the progression of OA.

In the past few years, substantial progress has been made in our understanding of the role of Toll-like receptors (TLRs) in inflammatory diseases. Joosten and colleagues discuss the role of TLRs in the pathophysiology of rheumatic diseases and how TLRs and TLR signalling pathways can be targeted to treat these conditions.

Family history remains a strong independent risk factor for developing rheumatoid arthritis (RA). This Review provides an overview of the ways in which familial aggregation has been evaluated, discusses what these studies can tell us about the aetiology of RA, and considers the potential value of family history of RA for clinical care and for research.

In comparative effectiveness research (CER) in the field of rheumatoid arthritis, the preferred source of data is drug and disease registries, whereas administrative health databases have commonly been used to examine safety and cost-effectiveness. Although the use of administrative health databases to investigate effectiveness poses unique methodological challenges, it also offers distinct advantages.

The influence of adipokines on the pathogenesis and progression of rheumatic diseases is increasingly appreciated. In particular, these factors have complex roles not only in inflammation, but in tissue remodelling. This Review focuses on the effects of distinct adipokines on bone cells and bone remodelling, and discusses whether these mechanisms could be targeted therapeutically.

The availability of new agents to treat patients with spondyloarthritis and the results of clinical trials published in the past few years provide new perspectives on the optimal management of these patients. In this article, Sieper and Poddubnyy review the current options for management of axial and peripheral spondyloarthritis on the basis of the latest evidence.

In this Review, Karasik et al. summarize key advances from the past 5 years in understanding the genetics of bone traits and osteoporosis. Despite the wealth of new genetic and genomic information, its application to the clinical management of osteoporosis remains in its infancy. The notable advances made in gene discovery suggest that the next decade will witness cataloguing of hundreds of genes that influence bone mass, which, in turn, will provide a roadmap for the development of new bone-focused drug targets.

Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis. Findings from studies in animal models and from clinical observations, particularly in relation to the effects of anticytokine biologic therapies, have led to new concepts of the pathophysiology of this phenomenon.

In patients with symptomatic femoroacetabular impingement (FAI), early correction of the anatomical dysfunction could delay or prevent the development of hip osteoarthritis. Accordingly, the past 5 years has seen a huge increase in minimally invasive, arthroscopic correction of FAI and a correspondingly rapid rise in FAI-related research. Khan and colleagues discuss the clinical evidence and emerging concepts of the pathophysiology, biomechanics and management of FAI.

In the setting of inflammatory diseases, metabolic profiling has potential applications in diagnosis, monitoring and defining disease pathogenesis. This Review focuses on metabolomic studies in rheumatic diseases, including discussion of state-of-the-art technologies, recent insights into disease mechanisms and treatment targets, and the feasibility of metabolomics for biomarker discovery.

This Review discusses the progress made by international networks in the USA, Europe and Asia towards improving the efficacy of existing and novel therapies for lupus nephritis. Strategies being actively pursued include biomarker identification and optimization of induction and maintenance treatment. These approaches aim to improve patients' outcomes by raising complete response rates, reducing renal flares, preserving long-term renal function, and minimizing treatment-related toxic effects.