Reviews & Analysis

The proinflammatory cytokine IL-17 is known to be an important factor in the pathogenesis of autoimmune joint diseases such as rheumatoid arthritis and spondyloarthritis, and therapies targeting this cytokine have shown promise. Although type 17 T helper cells are generally considered to be the main source of IL-17 in these diseases, the range of cell types that secrete this cytokine continues to expand; in particular, mast cells are receiving increased attention. Herein, the authors discuss the potential contribution of IL-17-secreting mast cells to inflammatory joint disease.

Early aggressive immunosuppressive regimens have fundamentally changed the treatment and management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, how to maintain remission in these patients is debated. Here, Raashid Luqmani considers how best to achieve maintenance of clinical remission in patients with AAV.

The IL-12 family cytokines contribute to immune-mediated inflammation and have an important role in determining T-cell fate. Evidence from preclinical and clinical studies suggests a role of these cytokines in the pathogenesis of rheumatoid arthritis (RA). The authors discuss these data and their potential clinical implications for patients with RA.

Small interfering RNAs (siRNAs) are a useful experimental tool to silence gene activity. The challenge, however, remains to optimize delivery and imbue 'drug-like' properties to siRNAs for therapeutic use. Here, the authors discuss advances in siRNA therapeutics and their potential application in treating rheumatic disease.

Crosstalk between the skeletal and immune systems—especially immunomodulation of bone turnover, but increasingly also regulation of immune functions by bone cells—was recognized during research into arthritis and has evolved into the discipline of osteoimmunology. Hiroshi Takayanagi presents an update of advances in this area, focusing on the influences of T cells on bone remodelling, and relationships between osteoblasts and haematopoiesis.

Alongside great sporting achievements, unfortunately, are inadvertent unwanted effects, as intense physical training in elite athletes can lead to long-term musculoskeletal issues. Here, Bennell and colleagues provide insights into the long-term consequences of sporting activity on the joint, in particular osteoarthritis, and describe how best to prevent and manage this damage in athletes.

In this article, the authors propose that clinical teams in the rheumatology setting are well-placed to facilitate self-management—and thereby improve health outcomes—by applying basic cognitive–behavioural techniques to helping patients manage disease-related psychological challenges and the impact of symptoms on their daily lives.

Tissue engineering and regenerative medicine hold great promise for the treatment of joint and cartilage destruction in rheumatic disease. Here, the authors describe the progress in this field, focusing on the clinical aspects of these emerging therapies and exploring the scientific and regulatory challenges in translating these tissue engineering approaches to the clinic.

Research in osteoarthritis (OA) is among the most collaborative in rheumatology, and the Osteoarthritis Initiative is championing efforts to pool expertise and data in imaging studies in OA. The rationale for, undertaking of, and emerging results from this project are outlined in this Perspectives article, with an emphasis on how they will advance the understanding and treatment of OA.

In the past decade, the introduction of targeted biologic therapies has revolutionized the treatment of rheumatic diseases. Patents for many of these key biologic agents will soon expire, and the introduction of biosimilar versions is likely to lead to substantial cost savings. Focusing on targeted therapies for rheumatic diseases, the authors describe biosimilar agent manufacture, safety and efficacy concerns, and the current worldwide status of regulations for the approval of biosimilar drugs.

Despite their different targets, biologic agents used for blockade of TNF and IL 6, inhibition of T cell co-stimulation and B cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. In this Perspective, the authors discuss the disparities in RA therapy and whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic RA cascade.

Radiographic joint damage is strongly associated with disability in patients with rheumatoid arthritis, but the relative importance of the two major measures of radiographic damage—bone erosions and joint space narrowing—is not clearly understood. In this article, the authors discuss this issue, and describe how imaging modalities that allow detailed visualization of cartilage might lead to improved understanding.